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Latest podcast episodes about Asco

Don Diablo Presents Hexagon Radio
Diablo Hexagon Radio Episode 361

Don Diablo Presents Hexagon Radio

Play Episode Listen Later Dec 29, 2021 59:13


This week we continue our festive specials with another very special Year Mix. Over 60 tracks released through Hexagon in 2021. 01. Rogerseventytwo - Live Forever Ft. Kita Menari (Extended Mix)02. Punky Monky - In The Name (Extended Mix)03. Future Class, Najjin & Eric Spike - About U (Extended Mix)04. Plastik Funk X Relanium & Deen West - San Francisco (Extended Mix)05. Greg Dela & Donkong - Dreams (Extended Mix)06. GSPR & PØP CULTUR - In The Stars (Extended Mix)07. Jack Shore - Out Of Love Ft. Jaime Deraz (Extended Mix)08. Olly Walker & Ollo Vera - Energised (Extended Mix)09. Faith - Giving Everything (Extended Mix)10. PØP CULTUR & HÄWK - Suga Suga (Extended Mix)11. Makay - Passkey Of Hearts (Extended Mix)12. TEN TONNE SKELETON - Tom's Diner Ft. Jasmine Ash (Extended Mix)13. Stadiumx & Kplr Feat. Clara Sofie - I Wanna Let Go (Extended Mix)14. OVSKY - On My Mind (Extended Mix)15. Lulleaux & Melsen - Break Me Down (Extended Mix)16. JLV - Sunset (Extended Mix)17. EC Twins - Love Me Your Way (Extended Mix)18. Promise Land X Danny Dearden - You Turn My Love Around (Extended Mix)19. Killfake - Rumor (Extended Mix)20. RetroVision - Whatever You Want (Extended Mix)21. KURA & Vedenzo - Meant To Be (Extended Mix)22. Dannic Ft. Lauren Dyson - Real Love (Extended Mix)23. Brian Cross & Taito Tikaro - Work (Extended Mix)24. David Puentez Feat. Fast Boy - Drive All Night (Extended Mix)25. Malarkey - Shackles (Extended Mix)26. Niiko X SWAE - Blah Blah Blah Ft. Mougleta (Boges Extended Remix)27. Loosid - Droids (Extended Mix)28. Melyjones & Eric Spike - Somewhere (Extended Mix)29. Tom & Jame, Tom Nash - Moses (Extended Mix)30. 7 SKIES - Pressure (Extended Mix)31. JustLuke & Inpetto Feat. Jordy - Drowning (Extended Mix)32. Swanky Tunes - Your Love (Extended Mix)33. Alex Skrindo - Like I Do ft. SMBDY (Extended Mix)34. Bancali - Follow You (Extended Mix)35. Asonn - Wild Ones ft. STRNGRS (Extended Mix)36. Mick Mazoo & NRDH - Ain't Even Trying ft. RoundRobin (Extended Mix)37. Raven & Kreyn x jeonghyeon - You & I (Extended Mix)38. Maurice Lessing - Magic (Extended Mix)39. ASCO, Nicola Fasano - You're not Alone (Extended Mix)40. Eastblock Bitches x Ostblockschlampen - Silver Surfer (Extended Mix)41. Leandro Da Silva feat. Sam Stray Wood - Get Lit (Extended Mix)42. Mo Falk - I'm Back (Extended Mix)43. Funkin Matt - Feelin ft. Tristan Henry (Extended Mix)44. SWACQ - Purification (Extended Mix)45. G-POL & Lambi - I WANT (Extended Mix)46. Dyro - Around (Original Mix)47. Sagan x Heyem & Groozin - Dreamer (Extended Mix)48. Landis - Weekday Anthem (Extended Mix)49. Ryan Coss & Dalic - Dream (Extended Mix)50. Jordan Jay - Maniac ft. Brenton Mattheus (Extended Mix)51. Antru - Shinjuku 1984 (Extended Mix)52. Gleb Filipchenkow - Toucher Toi Ft. Sainte Nicole X Indacity (Extended Mix)53. Dropgun – Stay ft. Boba Sheshera (Extended Mix)54. Castion - Never Give Up (Extended Mix)55. Moksi & Curbi - Famous Last Words (Extended Mix)56. NØ SIGNE & Emie - Be Good (Extended Mix)57. MOSKA & REK - Alcántara (Extended Mix)58. LOVRA - Lick It (Extended Mix)59. MorganJ ft. Kate Wild - Ain't Nobody (Extended Mix)60. DJ Kuba & Neitan x Nogun - Sweat (Extended Mix)61. Danny Avila - Hometown Heroes (Extended Mix)62. T & Sugah - Sky63. DJ Licious - Ripples ft. Ellie James (Extended Mix)64. Camp Kubrick - Whatchu Do

Disco Club -  Paul Jockey Official Podcast
Disco Club - Episode #073

Disco Club - Paul Jockey Official Podcast

Play Episode Listen Later Dec 28, 2021 60:18


PAUL JOCKEY (CRIMINAL VIBES) presents…DISCO CLUB #073Hi guys, this is my podcast called DISCO CLUB, you will find it every month with the best house tracks all over the world, turn up the volume and enjoy it!Ciao ragazzi, questo è il mio podcast chiamato DISCO CLUB, lo potrete trovare qui ogni mese con le migliori tracce house da tutto il mondo, alzate il volume e buon divertimento!TRACK LIST:1) Paul Jockey - Guantanamera (extended mix)2) Drop The Cheese - La Cola (extended mix)3) Bob Sinclar - Gym Tonic (wh0 extended remix)4) Sidepiece - Sextacy (extended mix) 5) Alex Nocere, Roy Batty - You Should Be Dancing (extended mix)6) Quattro, Bonsi - Ameno (extended mix)7) La Roux - Damaged Goods (huh oh remix)8) 2Hounds, Adriana Vitale, Anzo Gronso - Keep On Rising (extended mix)9) Asco, SoNick - Distraction (extended mix)10) Siwell - Goin Down (club mix)11) Lybera & Nick Morena - Echos (extended mix)12) Tuned Based - Let It Go (extended mix)13) Rootbox - In Da Ghetto (club mix)14) Pomella - You're Mine ( original mix)15) Dua Lipa - Levitating (luisdemark vip remix) YOU CAN FOLLOW ME ALSO ON:POTETE SEGUIRMI ANCHE SU:www.pauljockey.comwww.instagram.com/pauljockeydjwww.facebook.com/pauljockeyinfo, remix & worldwide bookings : management@gardenmusic.it

Como el perro y el gato
Carlos Rodríguez carga contra el hombre que arrojó a su perro desde un quinto piso en Nochebuena: "Asco de gente"

Como el perro y el gato

Play Episode Listen Later Dec 26, 2021 5:46


El hombre está siendo investigado por arrojar, presuntamente, a su perro desde la ventana de un quinto piso en la localidad madrileña de Valdemoro.

ASCO Guidelines Podcast Series
Management of Stage III NSCLC Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 22, 2021 11:44


An interview with Dr. Megan Daly from University of California in Davis, California and Dr. Navneet Singh from the Postgraduate Institute of Medical Education & Research in Chandigarh, India, co-chairs on “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline.” They summarize guideline recommendations on five subtopics – evaluation & staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daley from University of California in Davis, California, and Dr. Navneet Singh from the Post-Graduate Institute of Medical Education and Research in Chandigarh, India, co-chairs on management of stage III non-small cell lung cancer ASCO guideline. Thank you for being here, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you for having us. NAVNEET SINGH: Thank you for having us, too. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daley, do you have any relevant disclosures that are directly related to this guideline topic? MEGAN DALEY: I have research funding from EMD Serono, Merck, and Genentech. BRITTANY HARVEY: Thank you for those disclosures. Then Dr. Singh, do you have any relevant disclosures that are directly related to this guideline? NAVNEET SINGH: No, I have no financial conflicts of interest. BRITTANY HARVEY: Thank you. Getting into the content of this guideline, Dr. Singh, can you give us an overview of both the scope and the purpose of this guideline? NAVNEET SINGH: Yes, absolutely. So this guideline has been developed to assist clinicians involved in the management of patients with stage III non-small-cell lung cancer, or NSCLC, as we call it briefly. Now, stage III NSCLC represents one of the most heterogeneous subgroups of lung cancer. Consequently, it is also the subgroup in which the choice of multimodality treatment and the sequence of multimodality treatment varies significantly amongst clinicians, with variations being observed across institutes, as well as within an institute. And we sincerely hope that, with the help of this guideline, clinicians can accurately confirm the presence of stage III disease and offer the most appropriate treatment based on clinical and radiographic characteristics, as well as other medical factors that influence treatment decision-making. This evidence-based guidance also seeks to provide clarification on the common clinical dilemmas that clinicians may have while evaluating a patient with suspected or known stage III NSCLC. BRITTANY HARVEY: Thank you for that background information, Dr. Singh. Then, Dr. Daley, this guideline addresses five main sections, evaluation and staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. So starting with evaluation and staging, what are the key recommendations for workup for patients with suspected stage III non-small cell lung cancer? MEGAN DALEY: Our first recommendation for such patients is that they should undergo a history and physical exam and a CT scan of the chest and upper abdomen with contrast, unless it's contraindicated. If metastatic disease is not identified on CT, those patients should go on to a PET CT scan and MRI of the brain. If the patients are being considered for curative intent treatment, the guideline recommends pathologic mediastinal lymph node assessment. And we recommend that endoscopic techniques should be offered as the initial staging modality, if available. If not available, invasive surgical mediastinal staging should be offered. And finally, for patients who have suspected or confirmed stage III lung cancer, we recommend that multidisciplinary discussion should occur prior to any initiation of a treatment plan. BRITTANY HARVEY: Great, I appreciate your reviewing those recommendations. So following that, Dr. Singh, what does the guideline recommend regarding which patients with stage III non-small-cell lung cancer should be considered for surgical resection? NAVNEET SINGH: So in this guideline, the recommendation which has come forth is that for patients with stage IIIA, basically N2 disease, induction therapy should be followed by surgery with or without adjuvant therapy if several conditions are met. Basically, a complete resection of the primary tumor and the involved lymph nodes is deemed feasible, and three nodes or contralateral lymph nodes are deemed to be not involved, and the expected perioperative 90-day mortality is low, typically 5% or less. Another recommendation is that for selected patients with the P4N0 disease, surgical resection may be offered if medically and surgically feasible following multidisciplinary review. We would like to emphasize here that surgeons should always be involved in decisions regarding the feasibility of surgical resection. And they are an integral part of a multidisciplinary evaluation for surgical resection for stage III NSCLC patients. BRITTANY HARVEY: Great. Then Dr. Singh just reviewed who should be considered for surgical resection. So Dr. Daley, for patients with potentially resectable stage III non-small-cell lung cancer, what are the key recommendations for neoadjuvant therapy? MEGAN DALEY: Our first recommendation is that patients who are planned for a multimodality approach that will incorporate surgery should receive systemic neoadjuvant therapy. Second, that those patients with N2 disease who are planned for surgical resection should receive either neoadjuvant chemotherapy or neoadjuvant concurrent chemoradiation. And finally, for patients with a resectable superior sulcus tumor, neoadjuvant concurrent chemoradiation should be administered. BRITTANY HARVEY: Understood. Then in addition, Dr. Singh, for patients with resected stage III non-small-cell lung cancer, what are the key recommendations for adjuvant therapy? NAVNEET SINGH: So the panel came up with three recommendations for adjuvant treatment. The first is that patients with resected stage III NSCLC who did not receive neoadjuvant systemic therapy should be offered adjuvant platinum-based chemotherapy. The second recommendation which we came up was that for patients with resected stage III disease and presence of a sensitizing EGFR mutation-- classically, exon 19 deletion or the L858R exon 21 point mutation-- they may be offered adjuvant osimertinib, which is an EGFR inhibitor, after platinum-based chemotherapy. And this is based upon the ADAURA trial, which was published last year. And the third recommendation was that for patients with completely resected NSCLC and mediastinal involvement N2 disease, but without extracapsular extension, post-operative radiotherapy should not be routinely offered. BRITTANY HARVEY: OK. And then the last section of recommendations covers unresectable disease. So Dr. Daley, what does the guideline recommend regarding the management of unresectable stage III non-small-cell lung cancer? MEGAN DALEY: The guideline first recommends that these patients who have a good performance status should be offered concurrent, rather than sequential, chemoradiation, that concurrent chemotherapy delivered with radiation should include a platinum-based doublet, preferably cisplatin-etoposide, carboplatin-paclitaxel, or cisplatin-pemetrexed or cisplatin-vinorelbine. The patients who are not candidates for concurrent chemoradiation, but who are potentially candidates for chemotherapy, should be offered sequential chemoradiation, rather than radiation alone, that patients receiving concurrent chemoradiation should be treated to 60 gray. And that's based on the results of RTOG 0617. We also recommend within the guideline that doses higher than 60 gray and up to 70 gray could be considered for selected patients, with careful attention to doses to the heart, lung, and esophagus, among other organs. The guideline also recommends that patients receiving definitive radiation without chemotherapy, that hypofractionation using slightly larger doses could be considered-- over 2 gray per fraction, and up to 4 gray per fraction, and that patients without disease progression during concurrent chemoradiation should be offered consolidation durvalumab, based on the PACIFIC trial. BRITTANY HARVEY: Thank you both, then, for reviewing the key recommendations of this guideline. So, Dr. Singh, in your view, what is the importance of this guideline, and how does it impact clinicians? NAVNEET SINGH: I think this guideline will go a long way in helping clinicians who are involved in the diagnosis and treatment of lung cancer, especially stage III NSCLC. As mentioned earlier, this is a very heterogeneous disease. And there are several challenging situations, both in the context of diagnosis, as well as treatment. And using this guideline, which has an extensive evidence review, as well as the development of two very helpful algorithms, we sincerely hope that clinicians who are both in academic centers as well as in practice in the community are able to accurately diagnose stage III, appropriately stage it, and offer the best treatment, given the patient characteristics and the disease characteristics and available resources. BRITTANY HARVEY: Great. Those are important points. So then, finally, Dr. Daley, how will these guideline recommendations affect patients? MEGAN DALEY: Well, we hope very much that these guidelines will help patients consistently receive high-quality care for their stage III lung cancer. In particular, we're hoping that the recommendation from multidisciplinary assessment of patients prior to treatment is carefully followed. We're hoping that some of the recommendations surrounding the appropriate workup for patients may help ensure that all patients receive a thorough and complete workup prior to initiation of treatment. And the guideline, in particular, is highlighting some of the more recent developments in stage III lung cancer, such as the use of consolidation durvalumab based on the PACIFIC trial, the use of osimertinib in resectable disease based on the ADAURA trial. And we're hoping to make sure that these results are disseminated to practitioners everywhere so that patients can receive the latest and best care for their stage III lung cancer. BRITTANY HARVEY: Understood. Yeah, as you both mentioned, we hope that this has a positive impact for both clinicians and patients. So I want to thank you both for all of your hard work to develop this guideline and the evidence-based recommendations along with it. And thank you for taking the time to speak with me today, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you so much for having us. NAVNEET SINGH: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Adjuvant Therapy for Stage II Colon Cancer Guideline Update

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 22, 2021 17:42


An interview with Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from Dana-Farber Cancer Institute in Boston, MA, co-chairs on “Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update.” This guideline updates recommendations for adjuvant therapy for patients with resected stage II colon cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Nancy Baxter from the University of Melbourne in Melbourne, Australia, and Dr. Jeffrey Meyerhardt from the Dana-Farber Cancer Institute in Boston, Massachusetts, co-chairs on adjuvant therapy for stage II colon cancer ASCO guideline update. Thank you for being here, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you for having us. JEFFREY MEYERHARDT: Thanks. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines in ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Baxter, do you have any relevant disclosures that are directly related to this guideline topic? NANCY BAXTER: I don't, Brittany. BRITTANY HARVEY: Thank you. And Dr. Meyerhardt, do you have any relevant disclosures that are directly related to this guideline topic? JEFFREY MEYERHARDT: I don't, either. Thank you. BRITTANY HARVEY: Thank you, both. And getting into the content of this guideline, what prompted this guideline update, and what is the scope of this guideline? NANCY BAXTER: Well, it's been since 2004 that we've had a guideline that gives us advice about stage II colon cancer and the use of adjuvant therapy in this group of patients. And it's one where clinicians often have a lot of challenges in helping patients make decisions about what's best for them in terms of long-term survival from colon cancer. There have been changes in guidelines for stage III colon cancer. And so we thought it was timely to reevaluate our best practice recommendations for stage II colon cancer patients. JEFFREY MEYERHARDT: Yeah, I agree, Dr. Baxter. I think that this is one of the most challenging conversations that oncologists have with patients. Should they get chemotherapy? What type of chemotherapy? And as you know, there are a variety of higher risk features, of which we're able to sort of tease out a little better relatively, in terms of thinking about someone's stage II disease and trying to bring all that data together and provide some framework in the conversation for clinicians to have with patients. BRITTANY HARVEY: Great, thank you both for that background information. So then this guideline covers four clinical questions. And I'd like to review the recommendations for each question. So Dr. Baxter, starting with question 1, what does the guideline recommend for patients with resected stage II colon cancer regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy versus surgery alone? NANCY BAXTER: So overall, what we did was we looked at the risk that individual patients with stage II colon cancer have. So for patients that are at low risk of recurrence-- and so those are patients with stage IIA or T3 tumors that have at least 12 sample lymph nodes in the surgical specimen and don't have any high-risk features, and I'll go over those with the later recommendations-- these patients do not need adjuvant chemotherapy. It should not be routinely offered to them because the harms may outweigh the benefits. And so the evidence of that, although the quality of the evidence was relatively low, there is quite a bit of evidence that, really, the benefits do not outweigh the risks in this particular group. That is different for patients that are at higher risk, though, within the stage II group. And so those are the patients with stage IIB or stage IIC colon cancer. So those are T4 lesions that either penetrate through the visceral peritoneum or invade surrounding organs. And in those patients, adjuvant chemotherapy may have more benefit. And so a discussion of the potential benefits and risks of harms associated with chemotherapy should be had with patients. And those are patients that should be offered adjuvant chemotherapy for their disease. Now, there's a group of patients with high-risk features-- so not the stage IIB or stage IIC-- but there's a group of patients within stage IIA. So these are patients that are T3 patients where there are high-risk features. And chemotherapy may be offered to these patients, based on their risk features. So I'll go over a little bit about what the high-risk features are that might make patients included in this group. So that is sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poor or undifferentiated tumor grade, intestinal obstruction, tumor perforation, and grade BD3 tumor budding. That's more than, or equal to, 10 buds in the tumor. And so that's because these patients are at higher risk of recurrence, and the chemotherapy may be more beneficial in these patients because they have a higher baseline risk of recurrence. There were a few risk factors that it was really challenging to make any decision on. And that was specifically circulating DNA. We know that that's an area of great interest, but there really was not enough evidence of the predictive value of ctDNA when you're looking at adjuvant chemotherapy in this group to make a recommendation. We'd expect future versions of this guideline to have some recommendations about that. We do know that there is controversy around the timing of chemotherapy. So we didn't include reports on this for the guideline because we didn't have enough related to stage II colon cancer and the role of adjuvant therapy. But the trials have generally started patients on chemotherapy within six to seven weeks of surgery. And finally, all of this needs to be a part of shared decision-making. So particularly for patients at higher risk-- so stage 2A at higher risk-- it's important that this is discussed-- the risks and benefits of chemotherapy, and the possible benefits with respect to the risk of recurrence for these patients-- is discussed as part of the shared decision-making process to come to an ultimate decision about the use of chemotherapy. BRITTANY HARVEY: Understood. Thanks for detailing those recommendations stratified by risk and identifying what those high-risk features are. So then, additionally, Dr. Meyerhardt, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for patients with tumors that exhibit mismatch repair deficiency or microsatellite instability or patients with proficient mismatch repair, or microsatellite-stable, tumors? JEFFREY MEYERHARDT: Yeah, so this was a specific question that we also looked at. What we know is about 15% of stage II colon cancers have evidence of mismatch repair or microsatellite insufficiency. And data that was realized now several decades ago on several different papers-- one larger one published in The New England Journal by Dan Sargent-- showed that patients who have stage II disease who receive a fluoropyrimidine only seem to not benefit if they have microsat instability. And there was actually some evidence that they may actually have harm, or have a worse outcome. So it is not a routine recommendation to use a fluoropyrimidine-only treatment regimen in patients who have MSI-high or deficiency of mismatch repair in stage II disease. However, there are some qualifying statements that we reviewed and were important to think about in patients. So what we know is, again, some of those patients will have some high-risk features and particularly T4 tumors or some other high-risk features, except for poor differentiation, that the use of oxaliplatin may actually be a consideration in those patients. And that's basically from indirect evidence of a disease-free survival benefit with the addition of oxaliplatin in the population of patients with stage II disease that were included in the MOSAIC trial, one of the original trials that looked at the addition of oxaliplatin to a fluoropyrimidine as adjuvant therapy for colon cancer. We specifically carved out poor differentiate is not considered a high-risk prognostic feature in those patients. And so poorly differentiated tumors alone should not be a part of the decision in offering adjuvant therapy with a fluoropyrimidine or fluoropyrimidine-oxaliplatin for MSI-high or deficient mismatch repair protein tumors. And the other patients who have either proficient mismatch repair proteins or microsatellite instability are actually including the other parts of the guideline, so what Dr. Baxter just talked about and some of the other questions that we tackled that you'll be going to next. BRITTANY HARVEY: Great. Thank you for covering those recommendations for that particular patient population. So then, Dr. Baxter, if adjuvant therapy is recommended, is there a benefit to adding oxaliplatin to fluoropyrimidine-based chemotherapy? NANCY BAXTER: Well, this is obviously a question that oncologists will face when they're deciding to give adjuvant chemotherapy to high-risk stage II colon cancers or people with T4 stage IIB or C colon cancers. And you know, here's where it's challenging to make recommendations. Because we don't have a lot of evidence for this specific group. And this is why clinicians have such a challenge making recommendations for these patients. Because actually, there's insufficient evidence to routinely recommend the addition of oxaliplatin, meaning that we have to base our decisions on the best evidence that we have. And the best evidence we have, as we've talked about, is the MOSAIC trial. And so in the MOSAIC trial, a time to recurrence was longer with oxaliplatin-based adjuvant chemotherapy. And so it may be for some patients that the addition of oxaliplatin makes sense in terms of improving their overall outcome. And again, it needs to be a shared decision-making approach with the discussion of the potential benefits and risks of harms of the addition of oxaliplatin to fluoropyrimidine-based chemotherapy, so again, discussions between the oncologist and the patient. But that is with the exception of patients who are MSI-high. So those patients need oxaliplatin. If they're going to get chemotherapy, they shouldn't have 5FU-based chemotherapy alone, as we've just discussed. BRITTANY HARVEY: Great. And definitely, that shared decision-making is key. And I appreciate you reviewing the evidence behind these recommendations, as well. So then, the last clinical question addressed in this guideline, Dr. Meyerhardt, if adjuvant oxaliplatin-containing chemotherapy is considered, are outcomes affected by reducing the treatment duration from six months to three months? JEFFREY MEYERHARDT: Sure. So this was the last clinical question that the committee considered. And it is based on the IDEA collaboration. So the IDEA collaboration was the International Duration Evaluation of Adjuvant Chemotherapy. It was six trials that were done internationally-- one in the United States, one in Japan, and four in Europe-- that included patients both with stage II and stage III colon cancer. They receive three versus six months of therapy. Each of the trials had different chemotherapy choices in the sense that the United States trial, FOLFOX was the only choice that could be offered to patients, where in all the other trials, it was a physician and patient choice regarding the use of FOLFOX or capecitabine and oxaliplatin. And that, as people who know the data, is relevant to some of the discussion. And so the goal of the collaboration was to look at if we can give patients three months of therapy and not compromise outcome. And the main reason for that is we know that the peripheral neuropathy that's cumulative with oxaliplatin increases with more months of treatment. So patients who only receive three months of oxaliplatin have less likelihood of more significant cumulative neuropathy and will have less impact on function by receiving less oxaliplatin overall. Four of the trials included patients with stage II disease. And those trials, again, pooled their data and looked at the duration question in terms of for stage II patients. Those patients had high-risk disease, some high-risk feature, as discussed earlier. And what was shown is that for the patients, overall, there was not clear evidence of noninferiority with three versus six months. But when you looked at the patients who received capecitabine and oxaliplatin, the absolute five-year disease-free survival was 81.7% versus 82% for three versus six months of CAPOX, so essentially the same, with a hazard ratio of 1.02, and the confidence interval spanned across 1. And so those really didn't look like there was any compromise in outcome for patients to receive CAPOX for three months versus six months. For those patients who received FOLFOX, three months of chemotherapy led to a five-year disease-free survival of 79.2% versus 86.5% if you received six months of FOLFOX with a hazard ratio 1.41. So again, those data would suggest that if one was to choose FOLFOX, giving six months of therapy for high-risk stage II patients may be preferable to not potentially compromise some benefit in terms of disease-free survival. So again, the overall conclusion was it's a discussion with a patient regarding choice of therapy, whether receiving capecitabine, oxaliplatin or FOLFOX and then, based on that, consideration of the duration where we were most comfortable saying that three months of capecitabine, oxaliplatin is sufficient for high-risk patients when appropriate discussion between the clinician and the patient. BRITTANY HARVEY: Great. Thank you for explaining the nuance of that trial and your recommendation. So finally, to wrap us up, in your view, how does this guideline impact both clinicians and patients? JEFFREY MEYERHARDT: Yeah, so again, the last time ASCO had addressed guidelines for stage II patients was over 15 years ago. And there are more data. It was really early in the days of understanding the incorporation of oxaliplatin. There was no data versus the three versus six months. And there were less analyses trying to look at some of those particular high-risk features. So these are all important considerations in those discussions with stage II patients. And the importance of the guidelines are really to provide that framework on the various things you think about when you have a stage II patient and how to have those shared decision-making discussions with the patient. Again, it's not, probably, appropriate for all patients to receive adjuvant therapy, particularly lower risk. And even for higher risk patients, it is weighing the plus or minuses of the potential toxicities with what we know potentially are benefits. NANCY BAXTER: Yeah, I think that's very true. And I think, as anyone who treats colon cancer, or stage II colon cancer patients, is aware, this is not a homogeneous population. So in terms of the outcomes, there are people that do extremely well with surgery alone and people who, unfortunately, recur even after chemotherapy and surgery. And the future needs to focus on being able to differentiate those patients most likely to benefit from chemotherapy from those that are not likely to benefit. What we found in reviewing the evidence is we've moved forward from 2004, but we still have a long way to go. So I really hope when the next guideline is written that we're much closer to being able to identify those patients who would most benefit from chemotherapy in this group. Because we know there are patients who benefit from chemotherapy in this group. It's just we're still not perfect at identifying those people. So again, these conversations with patients are so important to talk about the limits of our knowledge, which I think is another important thing of this guideline is establishing what the limits of our knowledge are. But I think there are patients that you can confidently not give chemotherapy to. And that's very reassuring, both to clinician and to patients. And then this guideline kind of outlines the limits of our knowledge. And that's also important for clinicians and patients to understand. BRITTANY HARVEY: Definitely. I appreciate you both highlighting the importance of shared decision-making throughout this conversation that we've had. So I want to thank you so much for your work on this important guideline update and for taking the time to speak with me today, Dr. Baxter and Dr. Meyerhardt. NANCY BAXTER: Thank you very much. JEFFREY MEYERHARDT: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/gastrointestinal cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

Cafe Caliente Con Sammyvlog
Hombre toma a dos personas de rehenes en CDT de Añasco

Cafe Caliente Con Sammyvlog

Play Episode Listen Later Dec 22, 2021 1:42


Hombre toma a dos personas de rehenes en CDT de AñascoLas víctimas resultaron ilesas , Un hombre mantuvo esta mañana a una menor y una enfermera del Centro de Diagnóstico (CDT) en Añasco de rehén, reportó la Policía.Las autoridades indicaron preliminarmente que un hombre- de 37 años descrito con el cabello negro, con barba y quien vestía un abrigo negro y mahón- entró agresivo al centro hospitalaria a las 7:38 a.m. Luego, tomó a una niña de nueve años de rehén. Cuando la soltó, agarró a una enfermera, mientras sujetaba un arma blanca.Inf. https://www.primerahora.com/noticias/policia-tribunales/notas/hombre-toma-a-dos-personas-de-rehenes-en-cdt-de-anasco/

ASCO Guidelines Podcast Series
Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 21, 2021 15:53


An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, and Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, co-chairs on “Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline.” This guideline comprehensively addresses the treatment of brain metastases from non-hematologic solid tumors, including surgery, systemic therapy, radiation therapy, and timing of therapy. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, Virginia, Co-chairs on Treatment for Brain Metastases, American Society of Clinical Oncology, Society for Neuro-Oncology, and American Society for Radiation Oncology Guideline. Thank you for being here, Dr. Vogelbaum and Dr. Schiff. MICHAEL VOGELBAUM: My pleasure. BRITTANY HARVEY: Before we begin, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in The Journal of Clinical Oncology Dr. Vogelbaum, do you have any relevant disclosures that are directly related to this guideline topic? MICHAEL VOGELBAUM: I have no disclosures relevant to this guideline. BRITTANY HARVEY: Thank you. Then, Dr. Schiff, do you have any relevant disclosures that are directly related to this guideline topic. DAVID SCHIFF: Hi, Brittany. No, I do not. BRITTANY HARVEY: Great. Then first, Dr. Schiff, can you give us an overview of the scope and the purpose of this guideline? DAVID SCHIFF: Sure. Our overall purpose was to provide guidance on the appropriate treatment of adult patients with parenchymal brain metastases from solid tumors, encompassing surgery, radiation, and systemic therapy, as well. Previous guidelines in this area were for the most part produced by neurosurgeons and radiation oncologists for their respective professional organizations, although they did incorporate multidisciplinary input. But over the last decade, treatment options for certain types of brain metastases have undergone a substantial change. The expanding armamentarium for medical oncologists in treating both extra-CNS disease as well as brain metastases highlighted the need for a new set of guidelines to evaluate the role of systemic approaches, such as targeted agents and immunotherapy, for the primary treatment of brain metastases in the context of more established treatments like surgical resection, radiosurgery, and fractionated radiotherapy. Additionally, recent studies have clarified the role of radiation techniques like whole brain radiation with hippocampal avoidance and radiosurgery to surgical resection cavities. By assembling a multidisciplinary group of experts from surgical neuro-oncologists, medical oncologists, neuro-oncologists, and radiation oncologists, we sought to provide as comprehensive and up to date a set of therapeutic guidelines as possible. In order to accomplish this, the panel performed a systematic review of randomized as well as nonrandomized evidence from 2008 through April, 2020. We focused on the roles of surgery, systemic therapy, and radiation therapy, as well as the timing and interactions among these modalities. And we included all randomized clinical trials, as well as large single arm phase II studies and institutional case series, and we also reviewed case control and cohort studies. BRITTANY HARVEY: OK, great. That's helpful background. And then you mentioned a couple focus areas, as well, of the systematic review. And so I'd like to review the key recommendations that were based off that evidence. So, starting with surgery, Dr. Vogelbaum, what are the key recommendations for surgery in adult patients with brain metastases? MICHAEL VOGELBAUM: So, the role of surgery, I think, was well established via randomized trials to some degree, and then via some of the larger single arm studies. Patients with suspected brain metastases without a primary cancer diagnosis were felt to benefit from surgery to obtain a diagnosis and undergo removal of the tumor. But more to the point, patients with larger tumors with mass effect-related symptoms are the ones most likely to benefit from surgery. What we also noted was that patients who have multiple brain metastases with extensive and uncontrolled systemic disease are unlikely to benefit from surgery unless the remaining disease is controlled via other measures, typically medical measures. We also contemplated the type of resection performed, the technique being used. There was some developing literature looking at the techniques of either an en bloc resection or a piecemeal resection. And when we critically evaluated the literature, we felt that no recommendation could be made regarding the method of resection, as there was not sufficient evidence to support one approach over another. Another technique that is being used more recently is the use of laser interstitial thermal therapy, which is a minimally invasive technique to treat tumors in general. But again, there was insufficient evidence to really be able to make a recommendation for or against the use of LITT, as it's called. BRITTANY HARVEY: OK, thank you for reviewing both those techniques and those recommendations and highlighting where there wasn't enough evidence to actually make a recommendation. So, then, following that, Dr. Schiff, what does the guideline recommend for patients with brain metastases regarding systemic therapy, including chemotherapy, immunotherapy, and targeted agents? DAVID SCHIFF: Brittany, there is a role for systemic therapy as the initial or primary modality in some cases, but I think it's really important to emphasize this only pertains to patients whose brain metastases are asymptomatic and those with particular histologies or molecular profiles. So, there are really-- there are three primary sites for which targeted or immunotherapy can be considered. The first is non-small cell lung cancer, for which osimertinib, or if you're in China, where there's access to another drug called icotinib, specifically for EGFR-mutated disease, alectinib, brigatinib, and ceritinib are appropriate approaches in ALK-rearranged asymptomatic brain metastases. And finally, pembrolizumab in combination with pemetrexed and a platinum agent in immunotherapy naive patients whose tumors express PD-L1. The second primary tumor is melanoma. And for melanoma patients who have asymptomatic BRAF V600E mutant brain metastases, dabrafenib with trametinib is an appropriate option to consider. For all melanoma patients with asymptomatic brain metastases, ipilimumab with nivolumab is also an option. And finally, for breast cancer, the combination of tucatinib, trastuzumab, and capecitabine for HER2 positive asymptomatic brain metastases in patients who have progressed on previous anti-HER2 antibody therapy. When patients treated with systemic therapy progress intracranially, local therapies such as surgery, radiation, and radiosurgery should not be deferred. BRITTANY HARVEY: OK, those are helpful notes for clinicians, and particularly around the primary tumor sites. So, then, Dr. Vogelbaum, what are the key recommendations for radiation therapy in patients with brain metastases? MICHAEL VOGELBAUM: So, Brittany, the panel started by noting which patients would not benefit from radiation therapy, in particular, those with asymptomatic brain metastases and a poor performance status, with a Karnofsky Performance Score, or KPS, of less than or equal to 50, or performance status of less than 70 and no systemic therapy options. In those cases, radiation therapy is unlikely to be of real benefit. But then when speaking to the different modalities of radiation to be used, a lot of the review focused on the two most commonly used modalities, which is Stereotactic Radiosurgery, or SRS, versus Whole Brain Radiotherapy, or WBRT. And the first recommendation was that SRS alone as opposed to either whole brain radiotherapy alone or a combination of the two should be offered to patients with one to four unresected brain metastases, except for the situation of small cell carcinoma, which has a different approach that's used often with prophylactic cranial irradiation. So, that's a separate group. But for others, SRS is the modality that should be offered. And then for patients who underwent surgical resection of their brain metastases, we know that there needs to be some form of radiation treatment to the surgical cavity. And the recommendation was that SRS alone should be offered to those patients if the surgical cavity can be safely treated, and considering the extent of remaining intracranial disease. Obviously, for patients who have a lot of disease but otherwise have a treatable systemic disease, then whole brain radiotherapy may make more sense. But for the ones that are more limited after surgery, it should be SRS. And then when the panel considered a situation where you have patients with more than four unresected metastases and the options included radiosurgery, whole brain radiotherapy, or radiosurgery plus whole brain radiotherapy-- and in general, these are reasonable options. But it was felt that SRS may be preferred for patients with better prognosis or where systemic therapy that is known to be active in the central nervous system is available. Additional recommendations revolved around both protective, radioprotective, and radiosensitizing agents. So, in terms of trying to protect memory, there are two approaches that are used. One is to give memantine during whole brain radiotherapy, or to do whole brain radiotherapy using a hippocampal avoidance technique. And it was felt that either one of those or both should be offered to patients who will receive whole brain radiotherapy and have no tumors in the hippocampus, and they're expected to live more than four months. And then finally, that radiation sensitizing agents should not be offered to patients, because they've not been shown to be effective. BRITTANY HARVEY: Understood. And it's helpful to know both what those recommendations are for specific approaches, and as you said, critical to know who will and who will not benefit from radiation therapy. So, then we've just reviewed the key surgery, systemic therapy, and radiation therapy recommendations. Dr. Schiff, did the panel recommend anything regarding the timing of surgery, radiation therapy, and systemic therapy? MICHAEL VOGELBAUM: The panel had just a couple of points in this regard. Although there are some recent data suggesting a decreased incidence of leptomeningeal metastases in patients who undergo radiosurgery before craniotomy, as compared to the reverse sequence, the panel concluded no recommendation on this point regarding the specific sequence of therapy could be made. And to reiterate, for those circumstances in which systemic therapy may be of use for brain metastases, that therapy should proceed, local therapy like surgery or radiation, only if the brain metastases are asymptomatic. BRITTANY HARVEY: Great. Thank you both for reviewing these recommendations. In your view, Dr. Vogelbaum, what is the importance of this guideline, and how will it impact clinicians? MICHAEL VOGELBAUM: I think one of the important points that David raised that at the beginning was that this really is the most comprehensive look at the evidence revolving around the treatment of patients with brain metastases and leptomeningeal disease. And in particular, this may be new information for an audience that has not been involved in that treatment for many decades, the medical oncology community. So, I think some of the impact on clinicians may be that the guidelines will help them understand the durability of surgery and radiosurgery, and those had been the only treatments available for a long time. And so now we have these new medical therapies that are showing activity in the brain, but one needs to balance that against what is known about the effective treatments in the past. Some of the new targeted immunotherapies may not provide as consistent or durable of a benefit as has been shown previously with surgery and radiotherapy. Hopefully, understanding this challenge with respect to consistency and durability will serve to support the development of phase 0 or window of opportunity clinical trials to better understand the determinants the biological determinants of response or resistance to systemic therapies we want to improve on that, for sure, and those clinical trials are going to be essential for us to be able to do that. And then ultimately, also, identify opportunities to synergistically combine radiation and medical therapies and better understand the timing of these combinations. This is a great area for clinical trial development in the future. BRITTANY HARVEY: Definitely. We'll look forward to future research in those areas. So then, finally, Dr. Schiff, to wrap us up, how will these guideline recommendations affect patients? DAVID SCHIFF: Yeah. Over the last 30 years, the management of brain metastases have involved hugely, from an area where almost everyone got whole brain radiation therapy and many patients died from their brain disease. The use of local therapies like surgical resection and radiosurgery has greatly improved local control of brain metastases. And with options like radiosurgery alone for a limited number of brain metastases, systemic therapies as the initial approach, and hippocampal avoidant whole brain radiation therapy with memantine, patients are experiencing improved long term cognitive function and quality of life, as well. So, I think the careful delineation of the role of each of these modalities that these guidelines provide will really help maximize benefit and minimize the risk for this very large number of cancer patients. BRITTANY HARVEY: Definitely, improve quality of life is always a goal. So, I want to thank you both for your work on these guidelines and thank you for taking the time to speak with me today, Dr. Vogelbaum and Dr. Schiff. DAVID SCHIFF: My pleasure. MICHAEL VOGELBAUM: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

ASCO Daily News
Confronting Challenges in Oncology in 2022 With Dr. Derek Raghavan

ASCO Daily News

Play Episode Listen Later Dec 16, 2021 26:40


Guest host, Dr. John Sweetenham, associate director for Clinical Affairs at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and Dr. Derek Raghavan, President of the Levine Cancer Center at Atrium Health in North Carolina, discuss some of the major issues ahead for the oncology community in 2022, including tension caused by the COVID-19 pandemic, achieving true equity of care, how to use molecular testing in an optimized fashion, and the future of the oncology workforce. Transcript  Dr. John Sweetenham: Hello, and welcome to ASCO Daily News podcast. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and guest host of the podcast. Today, we'll be discussing the challenges ahead for the oncology community in 2022 with Dr. Derek Raghavan, President of the Levine Cancer Institute at Atrium Health in North Carolina. Our full disclosures are available in the show notes, and disclosures relating to all episodes of the podcast can be found on our transcripts at asco.org/podcasts. Derek, always a pleasure to have you here, and great to have you back on the podcast again.   Dr. Derek Raghavan: Hey, John. Always enjoy chatting together.   Dr. John Sweetenham: Derek, we're interested today to get your insights into what you think are going to be the major challenges facing the oncology community in 2022. I think each of us could come up with a pretty substantial list, but very interested to hear what you think are going to be those issues which are going to be uppermost in our mind as we move into the new year.   Dr. Derek Raghavan: Well, I think there are a number of important issues, John. I think everybody in clinical practice, medical or nursing, or whatever, have been brutalized somewhat by the COVID-19 pandemic, and I think everyone's tired and a bit cranky, and they're upset with a schism between the fringe and the science-based clinicians. So, I think that underscores everything. And there's an anxiety and a tension that I think is just new.   From the practical standpoint, which is where I think your question is directed, yeah, I think there will be issues that relate to achieving true equity of care. And I think hopefully, the focus will move from analysis paralysis to actually doing things and measuring outcomes. I think there will be the tension between value, price, and cost. People are spending an awful lot of money on health care. That's going to be an issue.   We have very good information on molecular prognostication, but a lot of the data that are coming out are from technologies that are not fully validated and not even standardized. There's a lot of disinformation and misinformation coming out, and I think we're going to have to address that. I think those are 3 themes that could keep us talking for quite a while.   I think the other thing, which is more up your alley than mine, is we've been watching CAR T[-cell therapy] emerge. I think we've got a beginnings of a pretty good handle on how CAR T[-cell] relates to hematological malignancy. It's much less clear in the solid tumors, and there is a bit of a tendency to do what used to happen in the 1970s and '80s, which is here's a new treatment. Let's give it a whack and see what happens.   But this is very expensive. We don't want to fall into the trap of how bone marrow transplant was introduced as a standard of breast care management for nearly a decade, based on somewhat flimsy evidence. So, we need to be a little more thoughtful about how we introduce CAR T[-cells] into the solid tumors.   Dr. John Sweetenham: Thanks. Yeah, plenty to discuss there, as you say. And what I'd like to do just because it is such a topical issue and continues to be at the moment is just pick up a little on the COVID-19 theme. I think that we've all seen a great deal of discussion in recent months about many of the consequences of COVID-19, including delayed screenings, late diagnosis, clinician burnout, and so on. But I'm interested in your insights on a couple of things.   Number 1, since we're now seeing the emergence of further new variants, what do you think that this is going to mean for the oncology community in terms of handling these new variants within the context of our patients with cancer? And then secondly, because I'm intrigued by one of the things you mentioned in our discussions about this podcast, you mentioned the changed relationship between health professionals and parts of the community as a consequence of COVID-19. And interested to hear you expand just a little bit on that. So, kind of 2 questions wrapped up in 1 there.   Dr. Derek Raghavan: Yeah. Well, I think the 2 are connected. The old style of physicians has always liked to be sure of their ground and to have a firm database when they talk about things. Particularly with the new variants, while it's completely appropriate to be transparent about the fact that they knew that they seemed different and so on, I think there is the problem that there are a lot of physicians who are now becoming TV personalities as much as physicians and who are talking all the time.   I'm not critical of that, but the problem is that they're being honest in saying we don't really know this, but this is what I think, and then they have to change direction. So, what's happening is, for the first time in a long time, physicians are regularly being quoted and being seen as saying things that are not necessarily correct, and that reduces confidence by the community and the physicians. At the same time, COVID-19, in my view, highly, inappropriately became a political football.   You have people who have absolutely no training, so radio hosts, football quarterbacks, basketball stars making extraordinary statements about COVID-19 and their approach to vaccination, masking, and other things where they have absolutely no business doing it. But they are people who are believed. They're high profile. And so, there's now a schism emerging between patients who listen to people who have no medical training at all and no basis for what they say and those particularly in the political domain who have politicized this and created a situation where, once upon a time, a physician was at least seen as coming from the right place and with good intent.   But we've both seen so many of these public demonstrations where physicians and public health physicians are being castigated for simply espousing good practice. Now, with respect to managing the variants, I think the fact is we have some basic principles that I have believed now for 2 years. Masks reduce the chance of getting any type of COVID-19. They just do. If you wear a mask most of the time when you're out and about, you're going to cut your chances down. Vaccination reduces the chance of ending up in the ICU unless you have some sort of immunological deficit.   Dr. John Sweetenham: Yeah. I'm going to switch gears now and return to the first thing that you mentioned right up front, which is the issue of equity and how we are going to address equity issues in the coming year. I think that in many ways, 2020, going into 2021, has been 2 years where issues of equity in health care have really come to the fore. And of course, there's been a great deal of discussion around this.   And I think you'd agree with me that we've seen, at the same time, that some of the strategies that we have been using during the COVID-19 pandemic, including telehealth, which one would have hoped would be a great equalizer, actually has the potential to exacerbate some of the disparities that we've been seeing in health care. But you mentioned analysis paralysis, and just to pick up on that theme, despite the huge amount of coverage that equity has received in medical journals and the media, where do you think we actually are in finally truly addressing some of the cancer care disparities that we see?   Dr. Derek Raghavan: Well, I think, John, you know that I was one of the early chairs of the ASCO Task Force. Otis Brawley and I chaired that task force together. Very early in the piece, I'm going to say probably 15 years ago, we wrote really quite a strong position paper on this whole issue. And so, we got started early in doing stuff on what we thought would be important, and we did, with support from the Komen Foundation, was to start training people of color in the oncology space and keeping them working in underserved communities by paying off their college loans for the period of time that they did that.   So, people have been doing stuff for a while. I think what's happened in the last decade, and it has been a slow change, is that there's been more a move to saying, let's get started. So, if you look at Chris Lathan up at Harvard, at one of their underserved hospitals, if you look around the country, consider the Bristol Myers Squibb Foundation, which puts money into active projects that are about doing stuff rather than having meetings to consider doing stuff. I think there's been that swing.   Dr. John Sweetenham: When we think about equity and disparities of care, we're often drawn towards the cost of cancer care and how much that plays into disparities and inequity in the delivery of cancer care. And picking up on that theme that you mentioned around value, cost and price, and maybe we could think about linking that with the use of CAR T-cell therapy and the application of CAR T-cells in the solid tumor world, if that is going to happen, what do you think we can do during 2022 to confront some of the cost and price issues that we're seeing within our cancer care environment right now?   Dr. Derek Raghavan: Well, I sometimes think in a utopian fashion, which doesn't get me very far, I have to say. What I'd love to see in the United States, because we spend far more money on everything health-wise than any other country in the civilized or uncivilized world, but what I'd like to see is a bipartisan initiative run by people who actually understand health care and health care economics that would go to the issue of, how do you get better bang for your buck? And it would include doing some tough things.   We waste money outrageously. We'll treat third-line metastatic pancreas cancer off trial. Nothing works in third-line metastatic pancreas cancer off trial. It's worth maybe a clinical trial to help the next person in line. That's how we make progress. But just to keep giving the same old litany of drugs in the hope that it might work is a waste of money. As I talked about before, BMT for breast cancer turned out to be a huge waste of money over a long period of time. So, if you can actually create a scenario where government set some rules and took the courageous, and this why it would have to be bipartisan, it would actually start to rationalize health care.   You know, John, the Oregon experiment many years ago, where one party started to rationalize care, and the other party accused them of rationing care. I mean, you can't have that happen. We've also seen both sides allocate the task of developing health care algorithms to people who are great politicians but know nothing about health care or economics. So, I mean, there are easy ways to do it. What we can do ourselves is be honest. Tell people what bang they'll get for their buck.   The person who is likely to have, say, an 80% chance of being dead within 4 months may not wish to mortgage his house if he's told that. On the other hand, he might well want to mortgage his house if he thinks that a very expensive treatment will give him the chance of being alive in 5 years. So, we, as physicians, shouldn't make that decision. It's the patient's right to be able to choose life versus the life of their offspring and spouse and future generations. So, I think it's not that complex, and I think if we brought more transparency about good expectations versus poor expectations, gave a better reason for patients getting more involved in trials, we're still at less than 15% of patients with cancer in the USA getting involved in trials, and that's a tragedy.   Dr. John Sweetenham: Yeah, I think also, the other thing that's occurred to me in this context, is the fact that while we tend to hone in on costs of treatment when we get into these discussions, I've been seeing some emerging literature around the cost of follow-up and unnecessary follow-up and imaging and so on in those patients who are in survivorship part of their cancer journey. And there's a huge opportunity there, I think, for us to reduce costs of care with no impact whatsoever on survival, no difficult treatment decisions to be made because we're simply doing an enormous amount of unnecessary testing in these patients who have completed treatment that we know doesn't impact survival. So, I do think that we could take a really serious look at that and make very significant savings. So, I think there's lots of potential there too.   Dr. Derek Raghavan: Yes. I agree, John. And I'd actually give kudos to ASCO in this space because they were early adopters of the Choosing Wisely campaign. They wrote two sets of guidelines about stupid things that we do that make no difference. And to be honest, I think that--I was on that committee, and the committee got tired.   I was one of the few people that actually felt we should keep going and very actively keep issuing guidelines of things that just aren't worth doing and having symposia at the ASCO ASM say that the symposia that are entitled “How to Waste Money” or alternatively entitled “How to Stop Doing Dumb Stuff” would be really quite important. And it would give the basis for sensible medicine to people who do medical legal protection work. So, most people who do multiple PET scans on lymphoma where the patient is completely well and blah, blah, blah are doing it for medical-legal reasons. They're not doing it because they think it will make a huge difference.   And I, of course, am not talking about the people where they're following PET scans as markers of response. So, I think we can do this work. I'd love to see a presidential campaign which is about not doing dumb stuff and where ASCO takes the bully pulpit and says, “we're spending a year policing ourselves, talking about all the things we do that don't actually make things better for patients.”   Dr. John Sweetenham: So, let's extend this theme of expensive therapies. And you mentioned CAR T-cell therapy. And in the hematologic malignancy world, we're now just beginning to see 1 or 2 results, which will be presented at the American Society of Hematology meeting in a couple of weeks from now, positive results from a couple of randomized clinical trials in hematologic malignancy with CAR T-cell therapy. So, what are your thoughts on the application of this treatment in the solid tumor world, and where do you think we are, what do you think we might see during 2022?   Dr. Derek Raghavan: Well, let's talk strategy first. I think a good place to begin is with a good scientific hypothesis. So, we both know how CAR T[-cells] work. We don't have to have a long discussion here about them. It would be patronizing to the audience. But you might think about, what solid tumor is actually going to benefit from immunological manipulation? Where have the checkpoint inhibitors been helpful, and where have they not been helpful? And so, you might focus the initial part of CAR T[-cells] and solid tumor work on those where there's a hypothesis that makes sense.   Then the second thing you could do would be to actually come to the companies that make all their money from CAR T[-cells] and say, perhaps you could invest in this research with us, and we'll do a couple of Hail Mary passes. So, let's look at the tumors where there isn't a good hypothesis, but nothing works, and see if we can get an experience. So, that'd be a nice, simple, easy way to do it. And then measure tight outcomes, have very robust entry criteria so you don't get confused about various toxicities because you're actually starting with patients in reasonable shape and then expanding to all populations.   So, the first part would be phase 1 and 2. Then you, early in the piece, make sure that you have inclusiveness so that you know all the population groups that might benefit from the treatment. I think that'd be a reasonable way to go.   Dr. John Sweetenham: Talking about identifying targets appropriately and target populations for treatment, you had mentioned as one of your other challenges for 2022 the concept around identifying molecular subgroups and molecular prognostication as a way of patient selection. So, could you say a little bit more about that and what you think we're going to need to do in the coming year in terms of refinement of targets?   Dr. Derek Raghavan: Well, John, this is an area of your expertise as well, coming from the hematological malignancy world. Now, I hope we would both agree that having robust reproducible technology is important. The fact that there are so many molecular diagnostic companies that hype their product doesn't necessarily mean that the product is good. So, there needs to be standardization of approaches to using technology, to measuring outcomes.   We need to have comparative sets of data, looking at different technologies to see how they work, and those sorts of studies need to be funded by government because there's no particular reason for the companies to agree to perhaps show that their diagnostic technology is not as good as somebody else's. But this would be a good initiative for the government to actually start to rank order of the products that are out there. I, frankly, think when you think of the impact of all of these molecular diagnostic tests, I've never understood why so many of them are out there without tight U.S. Food and Drug Administration (FDA) regulation. So, I think that's a place to begin.   If you think back to the old breast cancer days when there was immunohistochemistry and a bunch of molecular technologies, the outcomes were so varied when compared on common tumor samples. So, we just seem to be quite comfortable to make the same set of mistakes again. I do think there are responsible investigators doing excellent work in the space, so I'm not critical of the space. I'm answering the question, which is we need now to bring some regulation in to ensure that the quality of the work, reproducibility of the work. You'll even see, and I know you and I have talked about this in the past, there'll be Mr. X who has prostate cancer and gets his PSA measured, which is Prostate-Specific Antigen, looking at how active the cancer is regularly in different labs. That makes absolutely no sense. There's no common standard. PSA in my lab is going to be different from PSA in your's. And so there just should be some nice, simple rules of how to use molecular testing in an optimized fashion.   Dr. John Sweetenham: Yeah, and I wonder also whether we need to be looking a little bit more closely at point of care clinical decision support for some oncologists who may not be as molecularly literate as others because I do think that's another real challenge at the moment is giving guidance to everyone who might see these patients in terms of treatment selection.   Dr. Derek Raghavan: Well, I agree with you completely. I mean, kudos to the major companies because most of them provide pretty good decision support. One with which we worked tended to be a little too positive about its product, and we worked to change that. And now they're actually very useful. We have a big series from our molecular tumor board here that runs over I think a 5-year period that Carol Farhangfar, PhD, has just submitted for publication, which shows that you can heavily influence people who are out in the community by providing centralized support for their use of molecular diagnostic tests. But again, we only deal with the major companies so that we think there's good quality control there. And we don't flip back and forth in an individual patient between one company and another.   Dr. John Sweetenham: Right. Well, I think we're almost out of time, Derek, but I did want to ask you one more question, and it's a real change of gear. But over the last year or so, I think that probably largely because of the COVID-19 pandemic, we have seen some exacerbation of workforce issues in the oncology workforce that we knew already existed. I think there is undoubtedly more burnout being reported than there was before. Certainly, within our own organization, we have seen some increased staff turnover and a number of people who I think, frankly, have realized that they want to move closer to their families.   And so, there's been a certain amount of churn, which I think many of us in cancer centers are experiencing. Interested to know whether you've seen anything similar and what strategies you're using in terms of staff retention and oncology clinician burnout at your center.   Dr. Derek Raghavan: I think this is a difficult problem. The morale at the Levine Cancer Institute, much like the Simmons Cancer Center, is high, and that's driven by the leadership cadre being out there with their troops, visible and actively engaged so that the troops on the line feel that the bosses are part of the deal. And we do silly little things that matter, which is parties and celebrations and thank yous and all that sort of stuff. We get the staff to thank each other. We encourage the patients to thank the staff just with an attaboy or something that just says we appreciate the care.   So, I think this is a challenge. I do think work-life balance in old geezers like you and me has been a slightly different thing from some of the younger physicians who are spending, I think sensibly, more time with their families and don't want to spend these long hours. I think the other thing is there is still a town-gown issue where there are people who can make a lot more money much more quickly in some parts of non-academic practice, and it's getting harder to publish in academic practice, so the rewards for that are slipping a little.   I actually don't really have a solution. I think that the august colleges drawing to the attention of the world that this is a big deal and engaging bipartisan support from the political machinery will be important. I think ASCO can, through its government relations people (ASCO Advocacy), continue to prosecute these issues, which they do. I think there is the mistake that we make in the cancer space is we do still tend to compete between societies.   I've always thought it would be much healthier to have ASCO, ASTRO, ACS, SUO, SSO and all those people having a common council that speaks on this sort of issue with one voice and draws to attention of the people out there that this is a big issue. The best of the doctors (docs) are getting older. The younger docs come through the Taylor laws are less experienced and less well-trained and have a different ethos. So, we're going to lose an aspect of practice that's been part of the tradition of medical practice since the time of Osler, and it's definitely going away.   I have a superb physician fellow working with me at the moment who I would rate as one of the best 3 in 10 years. The reason she's one of the best 3 in 10 years is she practices the style of medicine that my fellows did 25, 30 years ago, most of whom are now professors of medicine somewhere. And good with patients, knows her staff, does research, and somehow manages to have reasonable time for a family. That tradition is starting to go away, and I don't think there is a simple change. And then the final point, the people who run health care today see it as a business. I was in a meeting recently outside my own domain where someone said, you know, I have to figure out whether medicine is really importantly a health care business or whether it's an IT business focused on health care. And that's going to start to lose the human side of medicine. We spent some time on that today. The outcomes will go down if this is just a business.   Dr. John Sweetenham: Well, thanks, Derek. Really appreciate all of your insights today. I think there's no doubt that 2022 is going to be a year of many challenges for those of us in the oncology community and for our patients, but I think it's also inevitably going to be a very exciting year in terms of new developments.   And hopefully, if we're recording another podcast like this in a year from now, the COVID-19 pandemic will be a little bit more in the rearview mirror, and we will be able to focus on many of the other important issues that face us. So again, really appreciate your sharing your insights with us, and wish you all the best for 2022.   Dr. Derek Raghavan: John, always a pleasure chatting, and the same to you and Caroline and the family.   Dr. John Sweetenham: Thank you. And thanks to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Derek Raghavan: Consulting or Advisory Role: Gerson Lehrman Group, Caris Life Sciences   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO.  The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Cancer.Net Podcasts
Targeted Therapy for Non-Small Cell Lung Cancer with an EGFR Exon 20 Insertion

Cancer.Net Podcasts

Play Episode Listen Later Dec 16, 2021 24:51


ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, experts will discuss targeted therapy for lung cancer, including 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells, called an EGFR exon 20 insertion. They will explain how targeted therapy works to treat cancer, why this specific mutation is different from other, more common EGFR mutations, and what these 2 new treatments mean for people with this type of cancer. This podcast will be led by Dr. Charu Aggarwal, Dr. Xiuning Le, Dr. Vamsidhar Velcheti, and Marcia Horn. Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer.  Dr. Xiuning Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas.  She is also a Cancer.Net advisory panelist for lung cancer.  Dr. Vamsidhar Velcheti is the director of thoracic medical oncology at NYU Langone's Perlmutter Cancer Center in New York, New York, and is also a Cancer.Net advisory panelist for lung cancer. Marcia Horn is the President and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group in Phoenix, Arizona.  View full disclosures for Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn at Cancer.Net. Dr. Charu Aggarwal: Hello and welcome to this Cancer.Net podcast on new research in lung cancer. I'm Dr. Charu Aggarwal from the University of Pennsylvania. I'm also the Cancer.Net Associate Editor for Lung Cancer. I'm here today with my colleagues from the Cancer.Net Lung Cancer Panel. First is Dr. Xiuning Le from the University of Texas MD Anderson Cancer Center. Hi, Dr. Le. Dr. Xiuning Le: Hi, everyone. This is Xiuning Le from MD Anderson. I'm happy to be here as one of the discussants. Dr. Aggarwal: Next is Dr. Vamsi Velcheti from the NYU Langone Perlmutter Cancer Center. Vamsi? Dr. Vamsidhar Velcheti: Hi, this is Vamsi Velcheti. I'm so glad to be here with you. Dr. Aggarwal: And our special guest today is Marcia Horn, the president and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group. Hi Marcia. Marcia Horn: Hi, everyone. Wonderful to be here. Dr. Aggarwal: So good to have you all. Before we begin, we should mention that Marcia has consulted with both Takeda Oncology and Janssen on survey research for the Exon 20 Group. You can view full disclosures for this podcast at Cancer.Net. Our podcast today is going to be about targeted therapy for non-small cell lung cancer, and specifically, 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells. This mutation is called an EGFR exon 20 insertion. Dr. Velcheti, I'll start off with you. What is targeted therapy, and how does it work? Dr. Velcheti: So thank you, Charu. Lung cancer is a very complex biological disease. There are a lot of genes in the tumor cells that could be mutated, and understanding the type of genetic changes or mutations in the DNA of these tumor cells helps us really develop treatments that are very focused on that particular patient's cancer. Having a specific gene alteration could render tumors more susceptible or vulnerable to certain treatments, and these are what we call targeted therapies. And in lung cancer, these are especially important because there are a lot of drugs developed for patients with certain unique genomic aberrations, or changes in the DNA, and it's ushered in a whole wave of new treatments for patients with lung cancer, and it's really an exciting time for patients with lung cancer. Dr. Aggarwal: That's terrific. And I would like to focus on the mutation aspect a little bit more. Dr. Le, can you talk to us [about] whether all mutations found in lung cancer, can all of them be treated? Dr. Le: Like Dr. Velcheti was talking about, lung cancer is really a complex disease. And oftentimes in 1 lung cancer, we can detect more than 1, multiple mutations. Some of them function as driving the cell growth. Some of them function as a brake. We call that a tumor suppressor to release the cell from being suppressed. Clinically, we usually classify all the mutations that can be detected in the lung cancer into the 2 groups. One is called actionable. The other group is called not actionable. Actionable, meaning when we detect a mutation, we, as clinicians, can actually offer a specific targeted therapy to act on the mutation. Therefore, detection of the actionable mutation oftentimes translates to the patient potentially having the opportunity to get targeted therapy targeting that potential actionable driver oncogene. As of today, we're talking, the development of lung cancer treatment has been so advanced. We have 9 actionable genetic alterations that can be detected in non-small cell lung cancer. Even since 2 years ago, there are 4 new additions, so a total of 9 as of today, and EGFR exon 20 is one of the newest being approved in 2021, so really good news. Dr. Aggarwal: I know we've come a long way, and EGFR exon 20 insertions have been known for a long time. However, we've also known that they are not perhaps as sensitizing as the other EGFR mutations. Dr. Velcheti, could you shed some light on what is unique about these mutations in terms of testing as well as application of therapies? Dr. Velcheti: We have known about EGFR mutations in lung cancer for a very long time, and there have been quite effective treatments for EGFR activating mutation-positive lung cancer patients. However, not all mutations in the EGFR gene are the same. Depending on the location of the sequence change in the gene, they could have a different degree of response to EGFR inhibitors. So when we talk about EGFR exon 20, we're talking about a subset of these EGFR gene mutations which is in an area of the EGFR gene, a change in the sequence of the EGFR gene, that doesn't necessarily respond so well to the novel EGFR inhibitors that we have been using for a long time. So the clinical implications, and it's something to kind of think about and remember, is that the way we test for these mutations is very different. You could do comprehensive genomic profiling, or in some cases, there are some tests that actually test for a specific type of gene mutation. So it's something we call “hotspot panels.” Those are tests using certain techniques that actually only pick up certain EGFR genes, and they don't pick up all the gene mutations that happen in the EGFR gene. So it is very important to kind of keep that in mind because now we have drugs approved for exon 20 mutations. If you don't actually pick them up on a test, then obviously, we can't identify those patients for treatment with these exciting new treatments. And also, just as a quick plug, given that we have so many new drugs approved for different types of gene alterations in lung cancer, it is even more important now to focus on doing really good biomarker testing with comprehensive genomic profiling looking at a wide panel of genes, rather than focusing on certain kinds of gene mutations. So this is what we call comprehensive genomic profiling. That's absolutely critical in order to identify patients for the right treatment with targeted therapy. So it's extremely important to do that upfront so that we have patients kind of matched up to the right treatment. Dr. Le: I do also want to add with Dr. Velcheti in that I fully agree that exon 20 is oftentimes not on the hotspot PCR-based testing, so please use a comprehensive, what we call, next-generation sequencing base. I also want to say that also, exon 20 can be detected in liquid biopsy. So it's not you have to do the tissue biopsy if the patient has the opportunity to get liquid biopsy. As long as it's a good, comprehensive panel, it should also be able to detect that. Dr. Aggarwal: Absolutely, can never underemphasize the benefits and importance of comprehensive testing. Marcia, I'll turn to you. You lead a large group called the Exon 20 Group. How common is the EGFR exon 20 insertion-- how common is this mutation in people with lung cancer? Marcia Horn: It's not at all common. In fact, EGFR exon 20 insertion mutations in non-small cell lung cancer are exceedingly rare, a total of about 2% of all NSCLC and about 9 to 10% of all EGFR mutations. And it's an insertion mutation that hits, for the most part, never-smokers and members of Asian populations, although we at the Exon 20 Group have seen diagnoses in virtually every racial and ethnic group imaginable. The Exon 20 Group was established in 2017 as a special project of ICAN. It was founded by an EGFR exon 20 insertion patient, Kevin Hamlin, and his brother, Bob Hamlin, who's a senior lecturer at MIT. What we all wanted to do was get an international working group put together, and before we knew it, we had this huge global coalition of not only many hundreds of patients for EGFR exon 20 insertion and HER2 exon 20 insertion representing about 54 countries, but we had care partners, family members, several hundred leading thoracic oncologists, medical oncologists, and members of the community oncology setting as well, plus biotechs, pharmas with drugs in the exon 20 pipeline, and members from molecular profiling labs and the basic sciences in exon 20 bench science. So altogether, we're working to turn this into a chronic and manageable disease, and for the last 4 and a half years, we've been connecting our patients to promising clinical trials, especially the 2 newly approved drugs, and our angel buddy program provides our patients with peer-to-peer counseling to help them through side effects. So we're all united in blasting this disease off the planet and making the patient journey far more manageable. Dr. Aggarwal: Incredible. I'm just so proud of what all you've achieved, and you serve such an important mission in terms of patient advocacy and, more importantly, support. Dr. Velcheti, there have been 2 new recently approved targeted therapies to treat non-small cell lung cancer that harbors an EGFR exon 20 insertion mutation, and really, these drugs have come to us within the last few months. How does the first drug, mobocertinib, work to treat this cancer? Dr. Velcheti: Yeah, definitely. I think this is a really exciting time for thoracic oncology as we have more to offer our patients, especially for exon 20 and EGFR exon 20 specifically. We have 2 drugs now, FDA-approved, and mobocertinib is a small-molecule inhibitor. It's an oral drug, and this has been approved for patients who have EGFR exon 20 mutation. This is for patients who have already had platinum-based chemotherapy, and they have progressed, and these patients could now be treated with mobocertinib. Certainly, the activity, it seems like a very active drug. It's very promising. It's kind of similar to the other small-molecule targeted therapies that we have, but it does have side effects. Patients could potentially have diarrhea, which is kind of similar to other EGFR small-molecule inhibitors or drugs in the class, so it's something to kind of know when patients are being treated with this drug. Certainly, it's really nice to have more treatment options for these patients. So I think now we haven't had any EGFR small-molecule inhibitors show significant efficacy in this patient population, so this is a really welcome approval for patients. And there's also a new drug, which I'm sure Dr. Le is going to be talking about, amivantamab, which could also be an option for these patients. Dr. Aggarwal: Speaking of, let's turn to Dr. Le about amivantamab. Can you tell us a little bit more? Dr. Le: Yeah, amivantamab, again, represents a very exciting approval. I think, like Dr. Velcheti was talking about, the small-molecule inhibitor, but amivantamab represents a brand-new class of potential agents for exon 20 and many other oncogene targets in lung cancer. So amivantamab, as the name signifies, is an antibody drug. It's not an oral drug. It's an IV drug. The antibody has 2 heads, basically. One is targeting EGFR. The other is targeting another oncogene called MET. So it's a bispecific antibody. The mechanism of action is also different than the small-molecule inhibitor such as mobocertinib in that it's not disabling the ATP-binding kinase activity of EGFR, rather than its antibodies to go after the EGFR on the cell surface and disable or internalize the receptor a different way. So I say that we're excited because it represents a really brand-new group of targeted therapy that we're probably going to see coming in the next decade, not just limited to the small-molecule inhibitor, of course, from the research, and also opens opportunity for future combinations. In terms of usage, so again, this medication is approved in patients who have EGFR exon 20 insertion, who had prior treatment. It's an IV treatment, and then the IV is rather frequent, every 2 weeks. The drug showed really great safety and then induced response in about 40% of the patients, a nice addition to the tools we have that we can battle the disease. Dr. Aggarwal: It's amazing that we have 2 drugs in this space. Can you talk, in your personal experience, pros and cons of each approach and if there is any data to guide using 1 drug versus another or in sequence? We'll start with you, Dr. Le, and then we'll go to Dr. Velcheti. Dr. Le: Yeah. So that's a very good question. I don't think we have the 1 perfect answer because we haven't conducted either head-to-head trials or sequential trials. When I'm in my clinic, I tell my patients that both of them are valid options. And most likely, 1 patient will be receiving 1 and the other because I think each of the medications also have a limit of after a certain time, the disease will continue to progress. So we shouldn't be ruling out either of them rather than thinking of them as being the sequential treatment. One thing I do also discuss with the patient is the drug administration - one is IV; one is oral - and then toxicity profile. The amivantamab, the most common issue is the infusion reaction in the first time that the patient's receiving it. However, after that's properly managed, the drug is really easy to tolerate down the line. So usually, I present both options to patients. I would have to say that numerically speaking, the response rate of amivantamab is higher than the reported of mobocertinib. So sometimes, together with the patients and family, we decide to go for amivantamab first and then save oral TKI as the next option, but really, there's no right or wrong. And then I tell the patient most likely, they will be receiving both in the end. Dr. Aggarwal: Your thoughts, Dr. Velcheti, on that approach? Anything different that you do? Dr. Velcheti: No, I completely agree with Dr. Le. Both of them are very different drugs. So Dr. Le mentioned they work in very different ways. They have, most importantly, very different adverse event profile. So we don't know about what the right sequencing should be. We don't have those studies to really inform us. But I do the same thing that Dr. Le just mentioned. Given slightly higher response rates, we tend to use amivantamab first, but again, it's really patient preference. I've had patients who said they don't want to have IV infusions. They prefer oral treatment. They don't want to come into the hospital that often. And there are some patients who are really concerned about the diarrhea. So it's really hard to kind of know what would be the perfect sequence, and especially, it's a rare population, so it's going to be really hard to do a trial, to kind of do a cross-trial comparison. That's all we have here in terms of making decisions. The other thing to also consider is, do we use these 2 drugs, one after the other, if they progress? I think given that they work in a very different way mechanistically, I do think if you progress on mobocertinib that doesn't necessarily mean you will not respond to amivantamab and vice versa. So I would encourage trying sequential approach. And also the other thing to also keep in mind is there are a lot of clinical trials with exciting drugs which are in the pipeline, and, of course, some of the data has already been presented and those look really promising. So I highly encourage patients to kind of consider participating in clinical trials. Dr. Aggarwal: That's such a fantastic summary. And Marcia, I will turn to you. What do these new drugs mean for patients with this rare subset of an actionable mutation? Marcia Horn: I totally agree with Dr. Le and Dr. Velcheti and their comments based on their deep, deep experience with EGFR exon 20 insertion patients. No question that, from the point of view of the Exon 20 Group, we were totally thrilled at the FDA approvals of both amivantamab and mobocertinib. And we, like everyone else, affectionately call both drugs as ami and mobo. These drugs are providing a concrete lifeline of hope, for the first time, that patients' lives can be extended and patient journeys can be manageable in terms of side effects. So what we're really excited about in the Exon 20 Group is not only the continuing clinical development of ami and mobo and other promising drugs in the pipeline, as Dr. Velcheti said, but we're looking forward to seeing ami and mobo in combination with second drugs. We're awaiting data down the road, obviously, from the ongoing amivantamab plus lazertinib trial that is recruiting, in part, EGFR exon 20 insertion patients, and we're really excited about drugs that can be combined with mobocertinib as well. We want a robust pipeline of numerous choices and good compounds. Dr. Aggarwal: And Marcia, given the amount of information in this subgroup, what questions should patients ask their doctors about these new treatments? Marcia Horn: We really think it's important for patients on diagnosis to ask their clinicians what the method of communication is going to be between patient and physician. This is not only important on diagnosis of EGFR exon 20 insertion mutated cancer, but it's really, really important when the patient is accessing either ami or mobo or a drug in clinical trials. So patients need answers on who is going to be answering their questions about side effects when they write those questions into a patient portal, and they have to have the sense that somebody is going to be listening to them in the event that the collateral medications that an oncologist may be giving them in conjunction with a clinical trial drug or in tandem with either ami or mobo-- if those collateral medications are not tamping down on side effects to the extent that we all want to see, we, for sure, want that patient to be talking to the treatment team, the study team, or whoever, and getting some quick answers because frankly, nothing is more tragic than a patient withdrawing from a drug for failure to manage toxicities, and we never want to see that happen. We do everything possible at the Exon 20 Group to make sure patients are outfitted with angel buddies who have lived, battle-hardened experience with that particular drug, and these drugs are manageable. Dr. Aggarwal: So much excitement going on in this space, and we are thrilled to be able to offer these approaches. But I will just summarize that we wouldn't be able to extend these benefits if we don't test, and comprehensive testing remains critical in diagnosing and delivering appropriate therapy. Thank you so much, Dr. Le, Dr. Vamsi Velcheti, as well as Marcia, for joining us today for this Cancer.Net podcast. You can learn more about lung cancer and how it's treated by visiting Cancer.Net. Thank you, everyone. Dr. Le: Thank you. Marcia Horn: Thank you. ASCO: Thank you, Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO eLearning Weekly Podcasts
Cancer Topics – Beyond Adjuvant Chemotherapy: Precision Oncology in Early-stage NSCLC

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Dec 15, 2021 31:03


Adjuvant immunotherapy is a game-changer for early lung cancer, but it is not the best choice for every patient. Through patient cases, Drs. Karen Kelly (University of California Davis) and Howard West (City of Hope Cancer Center) explore considerations in shared decision making and personalizing therapy. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 12/15/21

Más de uno
Josemi y Rosa: "La naturalidad es como la confianza que algunas veces da mucho asco"

Más de uno

Play Episode Listen Later Dec 15, 2021 9:07


Josemi Rodríguez Sieiro y Rosa Belmonte repasan en 'Más de uno' las últimas noticias de la prensa del corazón. Nos cuentan que Tamara Falcó y su novio han ido a una fiesta de cumpleaños disfrazados de Juego de tronos, que Cari Lapique se ha fotografiado con sus hijas, Cayetana Guillén Cuervo y muchos otros famosos.

Vernaculos
Vernáculos 63. Esquiar da asco

Vernaculos

Play Episode Listen Later Dec 13, 2021 189:10


Pues como hacia tiempo que no subíamos un podcast... aquí van 2 tazas, en este podcast tenemos a una invitada especial y hablamos de temas filosóficos y a parte hay un bonus track hablando sobre residente evil!

ASCO Guidelines Podcast Series
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 13, 2021 16:36


An interview with Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, MD, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, NY, co-chairs on “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline”. This guideline addresses evidence-based therapies for patients with newly diagnosed and recurrent gliomas. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING]   SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, New York, co-chairs on therapy for diffuse astrocytic and oligodendroglial tumors in adults American Society of Clinical Oncology and Society for Neuro-Oncology guideline. Thank you for being here, Dr. Blakeley and Dr. Mohile. SPEAKER 3: Thank you. SPEAKER 4: Thank you. SPEAKER 2: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guideline in the Journal of Clinical Oncology. Dr. Blakeley, do you have any relevant disclosures that are directly related to this guideline topic? SPEAKER 3: No, I do not. SPEAKER 2: Thank you. And Dr. Mohile, do you have any relevant disclosures that are related to this guideline topic? SPEAKER 4: No, I don't have any relevant disclosures. SPEAKER 2: Great. Thank you. Then let's get into the content of this guideline. So Dr. Mohile, can you start by giving us a general overview of the scope and purpose of this guideline? SPEAKER 4: Yeah, so over the past 10 years, there have been several positive clinical trials in various glioma subtypes, and several of them have demonstrated a benefit for chemotherapy. The primary purpose of this guideline is to help practicing clinicians understand how these trials might impact treatment for patients with gliomas. During this period, there's also been two updates to the World Health Organization classification of gliomas, and the terminology of gliomas has changed. So what we call tumors today is different from what we might have called them 10 years ago. And so a second purpose of our guideline is essentially to provide a key or a translator so a clinician can look at a pathology report today in 2021 with a current terminology and know what to do with that patient and what treatment best fits for that patient today based on what they would have been called in a trial several years ago. SPEAKER 2: Great. That makes a lot of sense. So then Dr. Blakeley, looking at this guideline, it addresses four clinical questions, which are after maximal safe surgical resection, what are the evidence-based therapies for adults with newly diagnosed glioma including optimal regimens, settings, and timing of therapy? Then also, what are the appropriate therapies for adults with recurrent glioma, including optimal regimens, settings, and timing of therapy, followed by what should the effect of MGMT promoter methylation status be on choice of therapy and if there are subpopulations that should affect the choice of therapy. I'd like to review the key recommendations for those clinical questions. In reading through the guideline, the expert panel provided recommendations based on the IDH mutation status and the diagnostic categories in the WHO 2016 and 2021 classification systems for tumors of the central nervous system. So it seems appropriate to review the recommendations in this manner as well. Starting with IDH mutant astrocytic and oligodendroglial tumors, what is recommended for patients with oligodendroglioma, IDH mutant, 1p19q deleted CNS WHO grade 2 or 3? SPEAKER 3: Absolutely, and I'll just summarize for our listeners to help simplify that as you said, essentially, all of the guidelines are divided along molecular markers. And the first cohort are 1p19q co-deleted gliomas. Something that is a 1p19q deleted gliomas also an oligodendroglioma. Those are interchangeable. If you are 1p19q co-deleted, you have oligodendroglioma and vise versa. In general, 1p19q co-deleted tumors also are IDH mutant. So you can consider that one bundle. And oligodendroglioma is something that is 1p19q co-deleted and IDH mutant. And for that whole classification, whether it's WHO grade 2 or WHO grade 3, the recommendation is for radiation followed by the combination of procarbazine, CCNU, and vincristine, based on two prospective studies that showed similar results at different time points. There are a couple of modifications to that guideline. There is a statement that if people feel that the combination of Procarbazine, CCNU, and Vincristine, also called PCV, is too toxic, they can consider temozolomide as an alternative for this subclass of tumors 1p19q co-deleted IDH mutant. And also, importantly, the 1p19q co-deleted grade 2 gliomas are some of the best performing tumors in terms of prognosis of all glial tumors and maybe all CNS tumors. And so there is a statement in the recommendations that say-- it says it is reasonable to defer therapy under appropriate circumstances. And the text goes into what those appropriate circumstances might be, including how much of a resection could be achieved, what the functional status of the person is, how old they are, et cetera. But big picture-- 1p19q co-deleted tumor equals an oligodendroglioma, and those are almost all IDH mutant. And the bottom line recommendation is radiation followed by PCV with the parentheses saying temozolomide might be a reasonable alternative to PCV, and if you have a particularly benign presentation with a grade 2 tumor, you can consider deferring that therapy start for a time. The next big bundle is astrocytic tumors that are not 1p19q co-deleted. So in the guidelines, those are termed as 1p19q non-co-deleted. And those tumors do come in two flavors-- IDH mutant or IDH wild type. And I'm going to focus on the IDH mutant because they track closer to the oligodendroglioma, but they are kind of a bridge between the very good prognosis associated with oligodendrogliomas and the more aggressive prognosis associated with malignant gliomas. And for this cohort, the 1p19q non-co-deleted IDH mutant cohort, the recommendation is for radiation therapy with adjuvant chemotherapy, and there is data that supports that adjuvant chemotherapy being either PCV or temozolomide. We don't prioritize between those two regimens. And why I'm highlighting the word adjuvant is in some centers, there is a tendency to use temozolomide concurrent with radiation therapy. And the recommendation for these 1p19q non-co-deleted IDH mutant WHO grade 2 tumors is not to use it concurrent but to use it in the adjuvant setting. And then I will round out with talking about IDH wild type. So now we're, again, 1p19q non-co-deleted but IDH wild type. Those tumors may act closer to the glioblastoma. And in that setting, we would say-- the recommendations say to treat with radiation and consider concurrent temozolomide as you would with glioblastoma or only adjuvant temozolomide as you would with the lower grade astrocytoma. SPEAKER 2: Great. Thank you for going through that and providing such clarity to those recommendations. Then following that, Dr. Mohile, moving on to glioblastoma and other IDH wild type diffuse glioma, what are the key recommendations for people with newly diagnosed glioblastoma IDH wild type CNS WHO grade 4? SPEAKER 4: So in the current classification, IDH wild type CNS World Health Organization grade 4 is what we've known of classically as glioblastoma. And for patients with glioblastoma who are fit and can tolerate therapy, we recommend treatment with radiation, concurrent temozolomide, and a six month course of adjuvant temozolomide. We also recommend that they can receive alternating electric field therapy along with the adjuvant temozolomide. Now the recommendations become a little bit more complicated for patients who might not be as fit-- so patients who might be older, have poor performance status, have other measures of frailty. And the way we wrote this is we said that if a patient who is undergoing a six week course of radiation, if that course of radiation, if the benefits did not outweigh the harm, then you could consider alternate regimens. And these include shorter courses or hypofractionated courses of radiation with or without chemotherapy and also includes courses that are chemotherapy alone. So in people who have tumors that have MGMT promoter methylation, we can consider the option of temozolomide alone. So this would be specifically for patients who either are older, more frail, who we feel are going to have difficulty going through a radiation course. There is some data to support this temozolomide alone approach. SPEAKER 2: Thank you. I appreciate you going through those recommendations very clearly as well. You clearly put a lot of effort into these recommendations. So then, Dr. Blakeley, what is recommended for patients with astrocytomas IDH wild type CNS WHO grade 2 or 3? SPEAKER 3: Yes, thank you. So as Dr. Mohile was just saying, for glioblastoma, you can really think about the recommendations for WHO grade 4 very similarly for IDH wild type independent of grade. And that is a new shift in the management of gliomas in adults. Previously, the histologic grading had a lot of weight on whether or not we would offer radiation and chemotherapy. But with the new prognostic and predictive value known associated with the IDH1 mutation or lack of mutation being IDH wild type, the recommendation is if somebody is IDH wild type CNS WHO grade 2 astrocytoma or grade 2 or grade 3, they would be offered treatment similar to a glioblastoma, which would be concurrent radiation and temozolomide followed by adjuvant temozolomide as long as performance status and all other factors support doing so. SPEAKER 2: Understood. I appreciate you providing that information as well. So were there additional areas where the expert panel found evidence either insufficient or was unable to make a recommendation? SPEAKER 4: Yeah, so there's two tumor types where we didn't have enough data to make a specific therapeutic recommendation. The first, unfortunately, is in recurrent glioblastoma. And there were no randomized controlled trials that demonstrated a benefit of one therapy over another. And so our recommendation is that when available, patients should be referred for a clinical trial. The other area is in a tumor type called diffuse midline glioma. This is a tumor characterized by the h3k27 mutation more commonly seen in children. But we do see this in adults. And here as well, there were no randomized trials that could clearly give us guidance on what the best therapy was even in the newly diagnosed setting. And our recommendation here also was, if available, to be considering a clinical trial. SPEAKER 2: Understood. It's important to recognize where there are areas where we're lacking evidence as well. So then, Dr. Blakeley, in your view, why is this guideline important and how will it change practice? SPEAKER 3: Thank you. Well, as Dr. Mohile said at the start, it is quite challenging to review the literature for gliomas in adults because we've had different nomenclature applied across clinical trials and diagnostic studies over the last 10 to 15 years. And this document and these guidelines really seek to be the clearinghouse to help clinicians match up what they see on the pathology report for their patient to the data that is published on phase III studies that has influenced our current standards of care. So I think the most important way it will change practice is bringing clarity to the data that already exists but has not been accessible to providers trying to help patients make the best decisions for them. It also importantly highlighted how much more work is needed. We desperately need new clinical trials for patients with glioblastoma and patients with astrocytoma IDH wild type 1p19q non-co-deleted WHO grade 2 and 3 and the other areas that Dr. Mohile highlighted. But we're hopeful that this will help provide clarity on both what we do know to help us identify patients who have the best chance of truly meaningful benefit from chemotherapy and where we need to invest more resources. SPEAKER 2: Absolutely. It seems like this will be a helpful resource for how to treat now and a guide as to what areas of research should be investigated in the future. So in addition to that, Dr. Mohile, finally, how do you view that these guideline recommendations will impact patients? SPEAKER 4: Yeah, my hope is that this will help standardize our approach to patients with gliomas. In the United States, patients with gliomas get care in all kinds of different settings. And when they're seeing an oncologist, particularly in the community, this might be a very small percentage of the types of cancers that they might be seeing, and it's hard to keep up with all of these trials and hard to keep up with the changes in classification. So our hope is that this guideline helps that oncologist in providing them the clarity, as Dr. Blakeley said, on how to approach treatment here so that all of our patients are getting the best standard of care based on the best available evidence and that they're being considered in those areas where there is not good evidence or referral for clinical trials so that in 10 years, when we put together the next guideline, that we're able to make some progress on some of these questions. SPEAKER 2: Great. Well, thank you both for all of your work that you did to review the literature and produce these evidence-based recommendations and, as you said, provide a real clear and helpful resource to both clinicians and to improve the quality of care for patients. And thank you for taking the time to speak with me today, Dr. Mohile and Dr. Blakeley. Finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Abemaciclib with Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update

ASCO Guidelines Podcast Series

Play Episode Listen Later Dec 10, 2021 8:55


An interview with Dr. Sharon Giordano, co-chair on “Abemaciclib with Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update.” Dr. Giordano discusses the results and impact of the monarchE trial, the updated recommendations on the use of abemaciclib, and impact for clinicians and patients. For more information, visit www.asco.org/breast-cancer-guidelines.

ASCO Daily News
Spotlight on Kidney Cancer With Drs. Toni Choueiri and Sumanta "Monty" Pal

ASCO Daily News

Play Episode Listen Later Dec 9, 2021 22:52


Guest host, Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, discusses the practice-changing KEYNOTE-564 and SWOG 1500 trials with Drs. Toni Choueiri and Sumanta "Monty" Pal. Dr. Choueiri is director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Dr. Pal is co-director of City of Hope's Kidney Cancer Program and associate editor of Cancer.Net. (This episode was recorded on 11/18/2021) Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and the professor of Medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome two internationally recognized leaders in the field, Dr. Toni Choueiri and Dr. Sumanta (Monty) Pal, for a discussion about two practice-changing studies in kidney cancer published this year-- KEYNOTE-564 and SWOG 1500. As a quick introduction, Dr. Choueiri is the director of Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute. He's also the Jerome and Nancy Kohlberg Chair, and professor of medicine at the Harvard Medical School. Dr. Sumanta "Monty" Pal is a professor in oncology, and co-director of City of Hope's Kidney Cancer Program, and he is an associate editor of cancer.net of ASCO. Our full disclosures are available in the show notes. And disclosures relating to all episodes of podcasts can be found on our transcripts at ASCO.org/podcast. Toni and Monty, what a day it has been for our patients with kidney cancer. I woke up with the news of the U.S. Food and Drug Administration (FDA) approval of the first ever adjuvant immunotherapy for patients with renal cell carcinoma. It is so great to have you both on the podcast today.   Dr. Monty Pal: Glad to be here. Thanks, Neeraj.   Dr. Toni Choueiri: Thank you, Neeraj. So glad to be here.   Dr. Neeraj Agarwal: So, let me start by asking questions to you first, Toni. So, you recently published the primary results of the phase 3 KEYNOTE-564 study, showing the efficacy of adjuvant therapy with pembrolizumab and immune checkpoint inhibitor in patients with renal cell carcinoma. And this study led to the approval of pembrolizumab this morning. So, please tell us more about the study design and why did you do this study.   Dr. Toni Choueiri: Thank you, Neeraj. And thank you, really, ASCO for this wonderful podcast series. And a big hit, I always listen to them when I'm driving or jogging. And really, thanks for this opportunity because kidney cancer adjuvant therapy has been something like a holy grail we're trying to find for a long, long time. The first adjuvant trial, a randomized trial, in renal cell cancer was in 1973 with radiation therapy. And since that time, all the trials except for one have been a complete failure in a way. And the first adjuvant immunotherapy trial was with old immunotherapy cytokine that we don't use much anymore and was in 1992. I was not done with medical school. I was not actually done with high school at that time, let alone medical school. And now that we have, as we all know, a revolution in the oncology field through these immune checkpoint inhibitors that reinvented immunotherapy in cancer, and now that pembrolizumab has shown activity in patients with more advanced disease, we thought about taking this into the adjuvant setting, a setting of patients where they were subjected to surgery. But on the pathology report, we knew that their risk of this cancer coming back, of recurrence, is somewhat intermediate high or high. These are patients that have stage 2 but grade 4, stage 3, D3, D4. These are patients that had node-positive resected. And we took even patients where the kidney is out, but, also, they had a removal of a metastatic site--let's say a lung metastasis--within a year of removing the kidney. And we know these patients we refer to as M1NED are at quite high risk of recurrence. And we randomly assigned 994 patients to receive pembrolizumab for a year versus placebo. And after a median follow-up of only 2 years--so I want to insist here that this is short for any trial in general--we saw a decrease in the risk of recurrence or death. The hazard ratio for disease-free survival was 0.68. So, a 32% decrease in the risk of recurrence or death. We looked at safety, and we already are familiar in the field of GU oncology with pembrolizumab. And we didn't see when we looked at the safety profile any surprises, any enhanced toxicity. Of course, immune-related adverse events are the number one concern with pembrolizumab. There were no deaths on trial related to pembrolizumab. We saw around 7% of patients needing high dose steroid to medicate these immune-related adverse event, and some patients had to come off therapy for that. We also took a look, Neeraj, an early look, at overall survival. We only had 25% of events, 51 deaths. And we did not meet the very rigorous statistical significance that is needed to say that study is positive for overall survival. But the hazard ratio was 0.54, a 46% decrease in the risk of death, which is kind of encouraging. And after a year, the curve starts to separate. Before a year, they're not separating. And that is consistent with prior studies in general.   Dr. Neeraj Agarwal: This is a very interesting point you just raised, that DFS, disease-free survival, is strongly positive. And even overall survival is trending in the right direction, right?   Dr. Toni Choueiri: Correct.   Dr. Neeraj Agarwal: That's great. So obviously, I would like to raise another point here. When we talk about adjuvant study, we usually think about a localized kidney cancer, which is removed by the surgeon, and then [the] patient is coming to see us for treatment in adjuvant setting. But this study, I would like to highlight, as you said, also included patients who had oligometastatic disease, had successful surgical removal of the oligometastatic disease, and they were also eligible for this trial.   Dr. Toni Choueiri: Yes, absolutely. And I think this is somewhat on the recent side in clinical trials in kidney cancer. The reason for that is that, in practice, we see those patients. And we even had two small trials in the TKI era with sorafenib and pazopanib, small studies, were also completely negative. So, we thought here that we should not exclude these patients. They end up being 6%, 7% of all participants, but this remains an area of unmet medical need.   Dr. Neeraj Agarwal: So, how is the hazard ratio in those patients who had metastatic disease removed and then treated with pembrolizumab?   Dr. Toni Choueiri: Yeah, it was very low. It was 0.2, so 0.29. And this was great to see. I don't want to go into really over-interpreting these results. All the hazard ratio--when you look at subgroup analysis or in the forest plot, all the hazard ratio are less than 1. We didn't see something--let's say 1.5--in favor of pembrolizumab. Now you go into a smaller subgroup, then your confidence intervals are very large and hard to interpret, except that to say, look, on average there could be a significant benefit here, but we can't tell.   Dr. Neeraj Agarwal: Sure, absolutely. I agree with you. So, how this is going to affect the current treatment paradigm, which is for patients with newly diagnosed metastatic RCC, where combination of VEGF-TKI plus immunotherapies (IOs) or IO/IO combinations have become standard of care or treatment paradigm?   Dr. Toni Choueiri: I do believe it will be a standard of care currently in the right population. There are a lot of unanswered questions, but that will be answered hopefully with more follow up. We have already, beside these results, reported--so these results were reported in the plenary session at the 2021 ASCO [Annual Meeting]. But later on, another analysis dealing with patient-reported outcome and quality of life was reported at ESMO and also showed no detriment in quality of life--that's the voice of the patient--no detriment with pembrolizumab (pembro). There is a lot still to do and a lot of unanswered questions, such as the non-clear cell histology, those patients who had surgery of their metastatic disease more than a year. But most important, I think, two questions. One, how can you know from the get-go who are the patients that need adjuvant pembrolizumab? We do not have any valid ctDNA. And I know Dr. Pal was involved with a lot of these type of research. We don't have any ctDNA test that is really that faithful and sensitive in the MRD space in renal cell. Many of us are working, so we don't know. We may end up over-treating patients that need surgery only. And actually, we may end up under-treating patients that need, perhaps, pembro, and another drug. And the second thing in those patients--and I hope it does not happen, but unfortunately, it will to some extent--whose tumor progress on adjuvant pembrolizumab, what do you do? What's the treatment paradigm? And actually, there is no data. This is a data-free zone. And I would think somebody whose tumor progressed, tumor continued to grow or grows, while they're actively on pembrolizumab, on IO, is way different than someone whose tumor comes back after 2 or 3 years from stopping the drug. Should we treat them with the same drug? Should we treat them with the TKI plus IO? Luckily, there are trials that are ongoing in patients whose tumor progressed after PD-1/PD-L1 inhibitor to give them a TKI as a control arm, or a TKI plus an immune checkpoint inhibitor. And I know Dr. Pal is very heavily involved with such trials. So, hopefully, we will answer this question, but not anytime soon.   Dr. Neeraj Agarwal: Very interesting, and definitely new results are posing new challenges in how we practice medicine here in the coming future. So, Monty, you are leading a trial with a very similar trial with atezolizumab. And I'm really hoping, we are all really hoping, that we see the other trial being positive, so we have more treatment options for our patients.   Dr. Monty Pal: I couldn't agree with you more. I mean, I definitely think that Toni's study really adds a lot of fuel to the fire suggesting that this strategy of adjuvant immunotherapy may be successful in localized renal cell.   Dr. Neeraj Agarwal: And I'm not going to really delve into the side effects of pembrolizumab and atezolizumab because these drugs are used quite often. They are in widespread use for different types of cancer. But just a quick question, any safety signal, Toni? Did you see any safety signal with pembrolizumab in this patient population?   Dr. Toni Choueiri: Yeah, this is an excellent question. So, nothing that would be different than using pembrolizumab overall knowing in other diseases as a single agent. So, this drug not first in human, as you know, and it's been approved in combination or as a single agent in many diseases. A tumor that the three of us treat is bladder cancer, and we know from another study how to use pembrolizumab. I think that the use of corticosteroid is somewhat of an objective way, at least to me, in looking at immune-related adverse event. And it has been between 5% to 10%, so we're not way off here. But there is no doubt that there are patients that we had no death on trial attributed to drug that may have, with pembrolizumab, some serious toxicities. We had patients that had autoimmune diabetes, hypophysitis, pneumonitis--quite uncommon, but not impossible.   Dr. Neeraj Agarwal: We'll still need to keep an eye for that, basically.   Dr. Toni Choueiri: No doubt.   Dr. Neeraj Agarwal: Yes. So, changing gears, let's talk to you, Monty. You recently presented the primary results of the SWOG 1500 trial in patients with metastatic non-clear cell renal cell carcinoma. Could you please tell us why you did this study and how this study's design was unique compared to similar studies in this setting?   Dr. Monty Pal: Yeah. No, absolutely. Toni did a great job of outlining areas that are sort of free of data in the adjuvant space, particularly with immunotherapy. I think that data-free area for us in kidney cancer for a long time has been non-clear cell histology. We just don't really know how to treat them. And I actually got advice from Toni when I was devising SWOG 1500. We planned it out as a very simple study comparing sunitinib and cabozantinib. And Toni will remember this history well. It sort of went through several iterations. The study blossomed into a six-arm trial. Ultimately, it turned into a four-arm study, looking at sunitinib versus cabozantinib versus two other MET inhibitors--savolitinib and crizotinib. And ultimately, the study was boiled down to essentially what we'd originally proposed. Two of the MET inhibitors--savolitinib and crizotinib--failed to surpass that initial analysis for PFS. So, ultimately, we demonstrated a superiority with cabozantinib over sunitinib for progression-free survival.   Dr. Neeraj Agarwal: So, what is the current treatment paradigm for patients who have newly diagnosed metastatic papillary RCC now?   Dr. Monty Pal: I think for patients who don't have genomic selection, I think that cabozantinib remains the standard. I really want to champion- and maybe Toni can talk a little bit more about this--a study that Toni is leading called the SAMETA trial, which I think has a really innovative design. And it's going to be genomically characterizing patients and randomizing to savolitinib with durvalumab or sunitinib. Tell me, Toni, if I have the design right there.   Dr. Toni Choueiri: Yes. Actually, this is a specific study in a specific population. It's not in papillary RCC as much as in those 30%, 40% of papillary RCC that have MET-driven tumors, so MET alteration, whether through chromosome 7 duplication, through chromosome 7 trisomy, through mutation or amplification. These patients will get either control arm or they will get savolitinib, which is a pure MET inhibitor that is devoid of VEGF-related toxicities, savolitinib plus durvalumab, or durvalumab alone. So, two experimental arms and one control. And the reason for this is we saw activity and quite a good toxicity profile with savolitinib, a pure MET inhibitor, over sunitinib in an earlier trial that was sunitinib against savolitinib in selected patient populations. The study had to close early. So, despite the numerical difference, this was not statistically significant. And then in another study led by Dr. Powles and colleagues, there was also some interesting activity how durvalumab could augment that activity. So, we're launching a phase 3 trial with three arms that you described very well.   Dr. Neeraj Agarwal: That's wonderful. So, what are the next steps, Monty? I mean, this is amazing to see you designing an investigator-initiated trial. This was your concept. You designed it. You built this to be a huge multicenter trial, which was open across the country, funded by the National Cancer Institute. And congratulations for making that happen. It's rare for us to see these trials going from a concept stage to a national trial, and then changing the standard of care. So, what are the next steps now for you and your team in SWOG for papillary RCC or metastatic papillary RCC? How do you build out further with the backbone of cabozantinib?   Dr. Monty Pal: I really appreciate the question, Neeraj. It's so critical to understand that we're just not quite done yet. Toni's study, as I've mentioned, is incredibly innovative. I'm also really thrilled to be working with someone who you've mentored so well, Ben Maughan, at the Huntsman Cancer Institute in Utah. And he's actually designed a brilliant study, which we're going to be leading together, which looks at cabozantinib with or without atezolizumab. Recently, in a study that you and I and Toni were a part of that we just published in JCO, we actually saw quite impressive response rates with the combination of cabozantinib and atezolizumab in patients with papillary RCC, around 47%. Those response rates were actually replicated in a separate study run by Joe Lee at Memorial Sloan Kettering. In the context of papillary disease response rates were again above a threshold of around 40%. So, I think there's something to it. But until we really subject this to randomization, I think we're not going to know whether or not cabo plus IO is standard. So, I encourage everyone to consider Toni's study. I encourage everyone to look out for our trial of cabo plus or minus atezo, which should be rolling out next year.   Dr. Neeraj Agarwal: What is the name of the trial, or the number, for our audience?   Dr. Monty Pal: Yeah, we lucked out with another great number. We got 1500 for the first trial. This is going to be SWOG 2200. So SWOG 2200, and I think it's due to open maybe in the first quarter of 2022.   Dr. Neeraj Agarwal: That's fantastic news. Any new signal? We know cabozantinib is already approved for our patients with metastatic RCC, courtesy METEOR trial led by Dr. Choueiri. Toni, it's amazing to see how many times you have changed standard of care for our patients with metastatic RCC. So, any new safety signal of cabozantinib in this patient population with metastatic papillary RCC?   Dr. Monty Pal: Nothing that appreciated. The toxicity profile was pretty much on par with what you'd anticipate for cabozantinib in the setting. Major side effects were hypertension, hand-foot syndrome, [and] diarrhea. Nothing that really sort of stood out relative to what we would expect in a clear cell population of patients.   Dr. Neeraj Agarwal: That's great. Any final messages for our patients, for our audience, for our listeners?   Dr. Toni Choueiri: Well, let me start, and maybe Monty can add. It's been, and it hopefully will continue to be, this humbling experience, where median survival from metastatic RCC in mid-2000--not long time ago during our training--has been 1 year. And now in metastatic disease, it's 4 to 5 years. And that is only going to get better. And then it's even more humbling to be in a time where you can talk about adjuvant treatment in this disease, renal cell cancer, that continues every year to kill, unfortunately, 14,000 Americans. That's just in the U.S. alone. So, we have to continue in getting more targets, more drugs, more reasonable combination, and the right patient, whether through specific biomarker that are tissue or blood-based or specific liquid biopsies that can tell you who has and who doesn't have cancer at the microscopic levels.   Dr. Neeraj Agarwal: Thank you. How about you, Monty? Any final message for our audience?   Dr. Monty Pal: I couldn't have summarized it better than Toni, just such a wonderful statement around optimism for what we've achieved so far and what's yet to come. And if I could emphasize to anyone in the audience today the need to keep progressing the field further with clinical trials, I think that would be my underlying message.   Dr. Neeraj Agarwal: Thank you again, Toni, Monty, for your valuable insights and thoughts. Thank you for all the inspiration. This is indeed so inspiring to see your work, which is changing the lives of our patients on a daily basis. Our listeners will find links to your studies in the transcript of this episode. I wish you all the best.   Dr. Toni Choueiri: Thank you.   Dr. Neeraj Agarwal: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you so much.   Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Pfizer, Merck    , Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Foundation Medicine, Gilead Sciences Research Funding (inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas   Dr. Sumanta (Monty) Pal: Consulting or Advisory Role: F. Hoffmann LaRoche, F. Hoffman Research Funding (inst.): Eisai, Genentech, Roche, Exelixis, Pfizer Travel, Accommodations, Expenses: Genentech, Seattle Genetics   Dr. Toni Choueiri: Employment: Dana Farber Cancer Hospital Leadership: Dana Farber Cancer Hospital, NCCN, KidneyCan, ASCO, ESMO Stock and Other Ownership Interests: Pionyr, TEMPEST Honoraria: NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group,                AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck          , Novartis, Peloton Therapeutics , Pfizer, Corvus Pharmaceuticals, Ipsen,                 Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Healthcare, Kidney Cancer Journal, Exelixis, Prometheus, Lpath, NEJM, Lancet Oncology, Cerulean Pharma, alligent, EMD Serono, HERON, Lilly, Janssen Oncology, IQvia, Aveo, and NCI. Consulting or Advisory Role: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus Laboratories, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, Paltform Q, Navinata Healthcare, Harborside Press, ASCO, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, ESMO, NiKang Therapeutics, Kanaph Therapeutics, Infinity Pharmaceuticals, and Aravive Research Funding (inst.): Pfizer, Novartis, Merck, Exelixis               , TRACON Pharma, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, NCI, GATEWAY for Cancer Research, and Congressionally Directed Medical Research Programs (DOD) Patents, Royalties, Other Intellectual Property (inst.): International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy, International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response Patents, Royalties, Other Intellectual Property: ctDNA technologies Travel, Accommodations, Expenses: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Healthcare, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO Other Relationship: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

ASCO eLearning Weekly Podcasts
Oncology, Etc. - From Personal to Politics – A Discussion about COVID and Oncology

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Dec 7, 2021 29:15


In this episode, oncologist Bryan Schneider and infectious disease expert Adrian Gardner from Indiana University, share what it has been like to get knocked down with COVID-19 twice, care for patients during the pandemic, lead the University's COVID response, and even a supreme court case on vaccination. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 12/7/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. PAT LOEHRER: Hi. I'm Pat Loehrer. I'm a director of the Centers for Global Health and Health Equity at Indiana University Simon Cancer Center. DAVE JOHNSON: And I'm Dave Johnson. I'm a medical oncologist at UT Southwestern in Dallas, Texas. PAT LOEHRER: Well, welcome back to ASCO's education new podcast series entitled Oncology, Etc. Today, we'll be joined by two outstanding guests, Dr. Bryan Schneider and Dr. Adrian Gardner. We're going to do a deep dive about COVID-19. And Dave, I was thinking-- I was reflecting on my life. The thing in medicine is when new diseases come out. So in our earlier lives, when we started there, was no such thing as Lyme disease, HIV/AIDS-- tumors didn't exist. And then just in the last couple of years now, we have COVID-19, the SARS CoV 2. And I think as physicians, it's kind of exciting. What's your experience been with the COVID-19 in the wards at Parkland? DAVE JOHNSON: Well, it's been really, very challenging. You know, I don't know that the public yet has fully grasped the magnitude of this disease. I mean, 700,000-plus Americans have died of this disease. That's an astonishing number when you think about it. And I was just on the general medical wards just a couple of weeks ago with a wonderful team of residents and students. Patients with this disease are very sick. We often downplay it, but I'm telling you, these people are really quite ill and can get ill and symptomatic rapidly, within hours. So this is a serious illness. But I agree with you. One of the things I told the residents a year ago was to keep a journal, that there are a few times during the course of your training and career where a new disease emerges, and you can be part and parcel of that. And keeping a diary of what happened is something that I wish I had done when AIDS emerged back in the '80s, or other disease processes, like Lyme, as you mentioned. PAT LOEHRER: And syphilis for you, wasn't it? DAVE JOHNSON: Well, that was sort of the [LAUGHS] Hippocratic oath days, but yeah, no. I think that was-- I think-- I can't remember. We were hanging out together at the time, so I don't remember exactly. Yeah, no, it's been really remarkable. The thing that's been interesting to me is the response of individuals and their families to the disease, particularly once the vaccines came available. So maybe we can delve into that a little bit today, because I know one of our guests has actually experienced that himself, so we'll know more about that later. PAT LOEHRER: I don't think, to be honest, that we could have a better collective wisdom than we have today with Dr. Schneider and Dr. Gardner, who will talk about their personal and professional and I think the global impact of COVID. I don't think there's any two people better than that. The only thing we could do better is if Anthony Fauci was here by himself. But these guys are tremendous people. Dr. Gardner went to medical school at Brown, did his fellowship and infectious disease at Beth Israel, and then did his MPH at Harvard, and joined the faculty in Indiana University in 2012. When he was a student, he spent time in Kenya, with Joe Mamlin from Indiana University as part of the AMPATH program. And he came back to become the field director there. And he is just an outstanding person. He's now the director of the Center of Global Health for Indiana University and the Associate Dean for Global Health and has led the contact tracing for Indiana University. And he's going to give us some input from this. Bryan, again, I've known forever. He's just an outstanding medical oncologist. He is now a Professor of Medicine and Medical and Molecular Genetics here at IU. He's a Vera Bradley chair of oncology. He is the founding chair of our precision genomics program and just a superstar in breast cancer as well as pharmacogenomics and was one of the first to describe the unique neuropathy associated with the taxanes in breast cancer. So it's just a pleasure to have both of you here. DAVE JOHNSON: You know, Pat, it's great to have that talent there. It balances out the negativity of other faculty members. But that's great. Welcome, both of you. PAT LOEHRER: I loved you a minute ago. I've turned mute on from a distance here. Adrian, tell me a little bit about yourself, growing up and how you got to where you were. ADRIAN GARDNER: Sure, thanks. And thanks so much for the invitation and for being part of this and for the generous introduction. So as you said, Pat, I'm a product of an international environment. That's an important part of my upbringing, actually. I was born in Scotland to two parents that-- born and bred in Scotland and grew up in Scotland. I spent the first six years of my life really living in France and then moved to Lawrence, Kansas, which was quite a cultural shift, but spent four years there. And it was great, actually, time in my life to be there, before moving to the East Coast, where I went to school and did all my medical training. So I'd had international experiences before, and I think that was an important part of my upbringing and something I sought for my kids, in the sense that it just immediately resets your sense of the world and makes you feel like a global citizen as opposed to just sort of more limited-- the community you're surrounded by. But it really wasn't until my experience as a fourth-year medical student at Brown that I had the opportunity to see health care in a low-resource setting and see that. And that was a very powerful experience professionally and personally. And as you said, it was the time when Joe Mamlin was really just dreaming up what the HIV response was going to look like, this nice institutional partnership that we'd set up in Western Kenya. But we set it up in the middle of the global pandemic. And true to our mission of responding and leading with care, felt a need to respond to the HIV pandemic. And that started really by-- was motivated by personal interactions that Joe had with some individuals who he saw firsthand come back to life, the Lazarus effect that has been reported. And that really spawned this whole response, changed my career and certainly my life, and had profound effects on my life. So that's a bit of who I am as an individual and how I got to where I am today. PAT LOEHRER: And we're going to touch on some of the work that you're doing now. But before I do, Bryan, tell us a little bit about and your background, where you grew up and how you got to where you are today. BRYAN SCHNEIDER: Thanks to you, and Dave as well, for having me on. And this will be an interesting perspective, because I think I'm coming on here as the patient this time, so it'll be a different view. But in contradistinction to Adrian, I am a pure Hoosier. I was born in the southern part of the state and raised there and then drove three hours north to Indianapolis, where I've set up for the last 25 years, and just been really lucky to be here at Indiana University. And Pat, you may not even remember this-- about 25 years ago, you were my formal mentor for med school, and so one of the influences and sticking around here along with some other real greats along the way. So have done, as you mentioned, breast medical oncology here in genomics and have had an absolute blast. So thanks for having me on. PAT LOEHRER: Oh, we love having you. And just as an aside, Bryan-- one is I think the world of you, and so proud of what you've accomplished. But Bryan's backyard actually was the home of Henry Lynch, and where he first described Lynch syndrome down in southern Indiana. And I think no greater tribute in his legacy than what you have done with precision genomics. It's really terrific. DAVE JOHNSON: Yeah. Maybe we'll have some time to delve into that. But actually, I'm curious, Bryan-- you mentioned that you've come on as the patient. My understanding is you've had firsthand experience with COVID, not just as a physician, but as the recipient of that wonderful new virus. Maybe you could tell us a little about that? BRYAN SCHNEIDER: Yeah, an interesting experience to be sure. So about 2 and 1/2 months ago, I tested positive for COVID and got really sick. Yeah, my three-year-old son had brought it home from his preschool and infected his older brother, who's almost 12, and then my wife and myself. And so was a really fascinating experience, I guess, and brought about some aspects to the virus that I had never really thought about. PAT LOEHRER: Now, Bryan, you also had COVID before, too. BRYAN SCHNEIDER: Yes. And the first time-- I was probably one of the very, very early cases and got really sick with it and lost my sense of taste and smell. I actually got one of the purple fingers, which I went to the ER for. I thought I was having a or something. And at the time, those weren't well-recognized symptoms. And that loss of taste and smell went months for me. So, yeah, I think I have frankly had the infection twice. The second time, though, was documented and certainly got really sick with the second one. DAVE JOHNSON: Can you elaborate on your second case? When you say you got really sick, was it a respiratory illness or were there other symptoms? BRYAN SCHNEIDER: Yeah, there were two aspects to it that were interesting. I think the first was physical. I got a sense of fatigue that I don't know that I have ever experienced before. It was one that I literally just could not get out of bed. And you know, I lost about 10 to 15 pounds from just being anorectic. And I'm not an overly thick human to begin with. But the big one was shortness of breath. And we had a pulse ox at home. My wife's a pediatrician, and I was sating in the high 80s. And I work out five or six times a week, so keep in pretty good shape, and I was stopping midway up the stairs to sit down, because I felt really tachycardic and just lightheaded. And so that degree of physical punishment is something like I have never expected or felt before. But the psychological part of it was really something I did not expect. And one part of that was an odd sense of guilt. I was getting texts and calls from a lot of friends checking on me, and many were baffled and asking, hey, did you not get vaccinated? Or what was going on with that? And so that-- it was a very odd sensation to me, because I, of course, had been vaccinated and I mask and all those sort of things. The other was one of real fear. I worried-- you know, luckily, I guess, our family all got infected around the same time, so we didn't have to think about quarantine. But I started wondering, could I have infected a patient? I take care of immunosuppressed breast cancer patients, before I was symptomatic. And then even after I came back to work, I had quarantined for quite some time, but I was really fearful. I would find myself double masking, washing my hands incessantly, and even holding my breath when I was trying to listen to heart and lungs during examination. So that sort of psychology was something I don't think I really expected with this infection. DAVE JOHNSON: How long did it take you to get beyond that, or are you beyond that part? BRYAN SCHNEIDER: Yeah. You know, I feel back to my baseline now. And I certainly don't worry about it on a day-to-day basis now. But my first clinic or two back was really hard for me, psychologically and emotionally. And part of me even wondered, should I profess to all my patients that I've had COVID? Or what things can I do to help protect them? And again, it was that mental aspect that I just didn't really anticipate prior to heading back to my clinic. DAVE JOHNSON: You know, this is eerily reminiscent of the physician who's had cancer who experiences extreme fatigue for the first time, chemotherapy-induced fatigue, after having described it many, many times before-- BRYAN SCHNEIDER: Right. DAVE JOHNSON: --and who has a guilt sensation in many respects as well. So quite the experience, for sure. PAT LOEHRER: Dave was talking about himself, by the way. BRYAN SCHNEIDER: No, I can only imagine. And you're right. We do try to paint a picture to patients about how things are going to feel, and it's amazing. When it's internalized or when you're feeling, it's-- it can often bring about a sense of, wow, I don't know that I-- I may have underplayed this to some of my patients in the past. And it really does provide some degree of empathy that's hard to capture if you haven't felt it. DAVE JOHNSON: So when I was on the wards, Bryan, I must confess, there were times when we walked into a patient's room with COVID who, of course, had not been vaccinated long after the vaccines were approved. Our professionalism prevents us from doing anything other than taking care of those people, but I'm wondering how you feel about caring for patients who have not been vaccinated or refuse to be vaccinated. BRYAN SCHNEIDER: Yeah. I mean, I think probably similar to a lot of people listening here today, it's a bit frustrating. And I think we all take care of patients who have a really tough diagnosis. And we're in the interesting field of giving patients medications that really immunosuppresses them, so we spend time counseling on the fact that you may get really sick or hospitalized or even die from neutropenic sepsis. And I think that is something that rests really hard with patients who are already dealing with a life-threatening diagnosis. And so now, trying to do that counseling in the face of a global pandemic like we haven't seen for a hundred years has really brought around a sense of duress and distress in my patients like I've never seen before. You know, I even had a patient who moved away from her family to be quarantined during adjuvant therapy, which I, of course, recommended against. But it really impressed upon me how big a deal this was. And so to see their frustration, and then in contradistinction, understanding that some people didn't want to pitch in to help-- it was very frustrating and honestly just made me very sad for people who I know were really struggling with this. DAVE JOHNSON: Actually, I had one more question to ask you. You mentioned coming back-- did you, in fact, share your diagnosis with your patients? I mean, I-- when I had cancer and came back, I made a pact with myself that I wasn't going to do that. But then I learned that the nurses were telling patients that I had cancer, and I found that it actually was helpful to share that diagnosis with many of my patients so that they could ask questions and feel that they had someone who really had experienced what they were either going through or about to go through. So I'm wondering how you've shared your diagnosis of COVID with patients, if at all. BRYAN SCHNEIDER: No, that's a great question. And I may have followed a similar pattern. At first I didn't. I didn't know what to do, to be frank. I didn't know if my saying that would make that patient, in that moment, more stressed out or worried, and I certainly didn't want to add to that. So I took it upon myself to try to make myself as safe to them as possible. But now that I've had a little chance to reflect on it, I have shared it. And I think for some of my patients, it's been good for them to hear what that experience was like. I think it's also-- Dave, as you probably know, I think it also reminds them we're human, too, and we experience some difficulty with physical health and I think in some ways it allows us to bond in a little bit deeper way. DAVE JOHNSON: I agree. PAT LOEHRER: I want to turn the attention over to Adrian now. Adrian, you're in a unique position, obviously one because of your experience in Kenya, and we want to hear about that, but also your responsibility for Indiana University. What some of the listeners may recall is that there was a decision made that you were part of that actually mandated that students in Indiana University be required to have vaccination before they came to school. We were in Kenya at the time when we heard that there was some consideration about that from the state legislature in terms of how-- mandating that. And eventually, this was a case that in which eight students took this case to cohort that eventually reached to Amy Coney Barrett, who decided to find in favor of Indiana University. It was a landmark decision here. But tell us a little bit about your experience on the leadership role of COVID and the impact that you see in terms of yourself personally and from the field of the university. ADRIAN GARDNER: Yeah. Thanks, Pat. I think it's really two different worlds in my mind, in some ways, although clearly linked by this global pandemic. You know, I was just finishing my eight-year stint, essentially, in Kenya in March of 2020 when we got the news that the entire world was about to be declared a level 4 by the State Department. And well, that-- I remember actually talking to Joe Scodro on the phone. And he's like, what the heck does that mean? That's not in our playbook of what we do when things happen and we need to bring trainees home and sort of-- PAT LOEHRER: Scodro being the lead counsel for Indiana University here. ADRIAN GARDNER: Thank you. Yeah, yeah. So for me-- I mean, obviously I was making a transition back to a US-based career in this position as the Director for the Center for Global Health. But you know, I had a dramatic change in my position, right? I mean, who is going to do global health operations in the middle of a pandemic? Well, nobody, because nobody was traveling. So we had really shifted all of our Kenya operations to a virtual support. We pulled all our trainees and long-term faculty back, initially. And my own position here is-- got pulled into a leadership role in Indiana University's response to the pandemic, along with three other physician leaders. And we all took on a different component of the response. So I was involved in the contact tracing, in part because we had some experience with contact tracing and global settings and tuberculosis and HIV. And while the transmission dynamics are obviously quite dramatically different and has different implications, but some of the principles around contact tracing were similar in the sense that contact tracing is not about really a stick, but it's more about extending a carrot and extending the support that allows you then to create an enabling environment-- and a quick phone call, in this case-- to allow people to identify what it is to quarantine and isolate effectively. To get to the Supreme Court issues and around mandates-- I think it was fairly obvious-- we were part of a restart committee that had been put together by the Dean of the School of Medicine, Jay Hess, and it was fairly noncontroversial among that group that we were going to need vaccine as we marched through this. And we immediately set up a lot of testing infrastructure and what we called mitigation testing at that point of asymptomatic individuals in addition to creating systems that enabled people to-- with symptoms, to enable testing very quickly and to get results back and to get that whole infrastructure in place. But it was pretty obvious to us-- it was a group of medical, public health, and ethics and legal folks-- that we were going to need a high level of immunity to get back to anything normal, right? And as we began planning for the summer and the fall of 2021, it was like-- it's a no-brainer. I mean, the only way you're going to get high levels of immunity, if you want to bring people back into the same classroom, if you want to have people living in dormitories, if you want to have them engage in the normal activities that college kids want to engage in, then you've got to have a very high level of immunity. And the only way to really achieve that is going to be through vaccine mandates. And again, it wasn't-- it didn't feel unprecedented, because you have to get a whole bunch of vaccines when you go off to college or when you go to elementary school. And that's really the only way to achieve that high level of coverage that allows us to not have a bunch of measles in our environment. And we still have mumps, despite high levels of coverage. But yeah, it felt weirdly noncontroversial. But of course, the whole politicization, I think, of the whole response to the pandemic made this more controversial. And clearly, there are people that feel very strongly about it. But I think this-- framing it in a context of personal freedom versus public good has not been particularly healthy for us as a country. I guess I'm not terribly surprised that the Supreme Court ultimately ruled against the preliminary injunction. I think the formal case is still pending, but it's maybe been overtaken by events, because now there are government mandates that are requiring vaccine or regular testing of just about-- lots of different industries and government employees and things. So I think it was important that we took a stand on this. And I think it has set a precedent, I think, for other universities. There were initially some hospital systems doing the same. But I think it's made it a lot easier to keep moving through industries and health systems with this kind of decision. PAT LOEHRER: Parenthetically, there's-- this week, they announced the-- we've reached over a million cases of COVID in Indiana. But the lowest county for infectious rate is actually Monroe County, which is where Bloomington is, where Indiana University is. And it's less than half of the rate of the state. And so I think kudos to you and the staff that have done this. Just maybe briefly, could you reflect on your experiences in Kenya, here in the United States-- lessons learned by you or by the university or by public officials about the contrast? I am reflecting now about a patient I saw today, that-- we were talking about the booster vaccine. And unfortunately, in Kenya, most people haven't gotten their first vaccine, either. So reflect a little bit about the global impact as you've seen personally. ADRIAN GARDNER: Yeah. So again, I think it's felt like two different worlds, but obviously struggling with the same thing, right? So I think on a global perspective-- so Kenya has-- Kenya got off to a pretty good start because they were kind of late to the game when it came to COVID, and they were able to jump on and learn from some of the lessons about physical distancing and shutting things down that actually enabled them to escape in the beginning. Of course, there was probably transmission going on behind the scenes that we weren't detecting, and even till now, the numbers that are officially reported are really just the tip of the iceberg. I think know that. Kenya has only reported 250,000 cases and just over 5,000 fatalities nationwide since the beginning of the pandemic. But there are serology studies that suggest that 50%, 60% of the population may have actually been infected-- at least, right? And that's based on blood donor studies and things. So I mean, I think some of the initial challenges, obviously, around access to PPE-- as we think about health care settings there, which are-- our partnership is based in, as you know. It's just the lack of infection control and the ability to even think about infection control because you're lacking space. As you know, Pat, in many of these wards in low-resource settings, there are two patients in every bed. And one might have active pulmonary TB and one might be getting chemotherapy for breast cancer. And it's less than ideal. But as you think about how to respond to that, it's pretty hard when you don't have any space, right? I mean, we did a lot here in terms of retooling space and utilizing space that was not being used and putting in negative pressure rooms where they were needed and this kind of thing that just weren't options in Kenya. One good news was that I think in Kenya, in particular, the testing capacity was able to get an early jump because the HIV infrastructure, PEPFAR, the President's Emergency Plan for AIDS Relief, had established seven regional laboratories that were obviously running HIV viral loads and so had PCR platforms. And they were able to rapidly retool those and convert them into COVID testing laboratories for PCR. So that was good, but then never really got to the same point where we need to get to, which is that it's readily accessible to everyone in rural regions and rapid testing in order to inform triage protocols [INAUDIBLE] patients and try to figure out how to develop that. So there's been testing available, but just not in the quantities that were sufficient. You know, I think we've been able to work across virtual platforms to share knowledge about management and clinical protocol development. That's been another success story. Certainly our partnership is longstanding and so has allowed those relationships that have withstood the test of nonpersonal interaction. And of course, the biggest elephant in the room now is this issue of vaccine equity, as you pointed out. So about 5% of the population in Kenya has been vaccinated. Part of that is vaccine access. Part of it is probability distribution infrastructure. Think about low resource settings-- many of them do quite well with vaccine delivery, but they're early childhood vaccines, right? So they have whole infrastructure around maternal child health that's set up to do this. There's not a lot of infrastructure for rapidly mobilizing 50 million adults to try and get them in for a two-shot series. So how do you do that? I mean, yes there are some community assets in terms of community health workers and things, but so far, at least, the vaccine quantities available have not been sufficient to allow that kind of infrastructure to really take over, at least in Kenya. But it holds promise, I think. But then they also are up against the same, I think-- some of the same challenges that we face here in terms of vaccine misinformation and lack of trust. This is an area where I think trust is really key ingredient in health systems, and I think we've seen it in our own inequalities that have been made very, very obvious in our own country and really, the issue globally. And it's not a new lesson. We knew it from Ebola and other very obvious infectious diseases that have resulted in high degrees of death because of lack of trust. When I have taken care of patients here and I've had those same experiences that Dave was talking about earlier, where you want to just ask the patient, so why didn't you get vaccinated? As an infectious disease provider, we've been called in to a lot of these cases, and I've taken the opportunity to ask a couple of times-- not in a judgmental way, but trying to set the stage and just-- what is it about the system? And a lot of-- some of it is misinformation. Some of it is this politicization and political bias. But some of it is just a very subtle mistrust and this notion that you don't feel completely welcomed or resected within the health care setting. And that's enough to just turn it off to this point where, eh, I'm just not ready to do that. And I think that's sometimes more subtle than we appreciate, but it has a huge impact. DAVE JOHNSON: We're getting close to the end of our time. I want to pivot back, if I may, just for a quick moment to Bryan. This may be an out of-- from left field type of question, but we learned a lot about early chemotherapy from the infectious disease world. We took some of the infectious disease principles and applied them in the early years of chemotherapy. Do you think there's much to be learned from a precision medicine standpoint from the COVID pandemic? What are you taking away from not just your personal experience but the larger experience, if anything? Or is that just-- is it just too early to say? BRYAN SCHNEIDER: No, I mean-- I think I've always admired the speed and efficiency with which breakthroughs have happened in infectious disease. And I mean, the idea of a brand new virus coming on board a couple of years ago and coming to the point where we are today shows, I think, real innovation, but the ability to get behind a question and, as a community, answer it well. And I think from that standpoint, that's something that all disciplines, including oncology, can learn. I certainly think we're seeing more and more intersection, too, with the way we think about treating cancer and its impact on immunity. And so certainly in that way I think there's real connections. But I do think some of the innovations that were brought about from the NCI with the vaccines are going to really also herald in things that will be game-changers in the world of oncology and therapeutics as well. DAVE JOHNSON: That's great. PAT LOEHRER: If I can throw in something, too-- I think, Dave, particularly as we talk about global health, many of the cancers that we see in the low-to-middle income countries are caused by viruses. One of the number one causes of cancer in sub-Saharan Africa is cervical cancer. We could eradicate that by getting vaccines out there. In terms of the lessons learned, I think the lessons learned in oncology is that we need to deal more with population health and with prevention than we do with the treatment towards the end of the life. And hopefully that will be a lesson that we can take home with us around the world. ADRIAN GARDNER: Yeah, and Pat, I think we do need to do better as a global community in terms of sharing vaccine and getting manufacturing up, and not just for vaccines but PPE and therapeutics. It's just not fair, the world we live in now. And at least we all know that and we take it for granted in some ways. But it shouldn't be this unfair, right? And that's been part of the problem globally, and it's part of the problem in the United States. DAVE JOHNSON: Yeah. PAT LOEHRER: But the tail end also is access to drugs for chemotherapy, too, and to have radiation available for all these patients. So it is-- this access is an important part of health equity globally. And I think it behooves all of us to be involved with this mission. DAVE JOHNSON: Well, again, we've come to the end of our time. And we want to thank all of our listeners, but most of all, we really want to thank Bryan and Adrian for a wonderful interview. We really appreciate your time and you sharing your experiences with us. Thanks again to the listeners for tuning in to Oncology Etc. This is an ASCO educational podcast. We want to talk really about anything and everything, so if you have an idea for a topic or a guest, we invite you to share that with us and email us at education@ASCO.org. So thanks again. And remember, Pat, I before E except after C. PAT LOEHRER: [LAUGHS] Well, I'll see you later, then. DAVE JOHNSON: No, wait a minute. Wait a minute. Eight, leisure, sovereign, weight, weird, foreign, vein, neighbor-- apparently it doesn't work. [LAUGHTER] My second-grade teacher taught me that rule, and it's just wrong. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

Penguin Audio
Audiolibro: ¡Qué asco de bichos! - Roald Dahl (Español-Latino)

Penguin Audio

Play Episode Listen Later Nov 23, 2021 1:10


Escucha este audiolibro completo: https://bit.ly/3l1UBZNNarrado por: Beto Castillo¡Qué asco de bichos! está compuesto por nueve historias en verso que se caracterizan por su originalidad, humor y su desbordante imaginación...#penguinaudio #audiolibro #audiolibros #Roald #Dahl #RoaldDahl See acast.com/privacy for privacy and opt-out information.

Journal of Clinical Oncology (JCO) Podcast
JCO After Hours: A Discussion With Kirsten Beyer and Jennifer Griggs

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Nov 19, 2021 26:09


Dr. Shannon Westin, Dr. Kirsten Beyer and Dr. Jennifer Griggs discuss how mortgage lending bias and residential segregation intersect with cancer disparities and survival outcomes.   TRANSCRIPT [MUSIC PLAYING]   SHANNON WESTIN: Hello, everyone. My name is Shannon Westin, and I'm an Associate Professor at the University of Texas MD Anderson Cancer Center in the Department of Gynecologic Oncology and Reproductive Medicine. And I currently serve as the Social Media Editor for the Journal of Clinical Oncology. And we're starting a brand new podcast series to try to bring really exciting research that's being published in the JCO to you, and I'm so excited to kick off this series with a group of very accomplished women who are covering something that I don't think a lot of us don't know very much about. So I'm really excited to learn a ton over this next few minutes. So it's my pleasure to introduce Dr. Kirsten Beyer, who is an Associate Professor in the Division of Epidemiology in the Institute for Health and Equity as well as the Director of the PhD program in Public and Community Health at the Medical College of Wisconsin. We are also joined by Dr. Jennifer Griggs, who's a Professor the Department of Internal Medicine, Division of Hematology Oncology, as well as a member of the Institute of Health Care Policy and Innovation at the University of Michigan. She does predominantly practice taking care of women with breast cancer. Welcome, doctors. JENNIFER GRIGGS: Thank you. KIRSTEN BEYER: Thank you very much. SHANNON WESTIN: So we're talking today about the manuscript "Mortgage Lending Bias and Breast Cancer Survival Among Older Women in the United States" that Dr. Beyer published just this month in the JCO. In addition, Dr. Griggs and her colleague Dr. Pleasant were invited to participate in an editorial called "Contemporary Residential Segregation and Cancer Disparities." So let's get into to what was covered. So I think for me, the lowest hanging fruit here, Dr. Beyer, is understanding what exactly is redlining, because that was one of the critical exposure that you were assessing amongst these women with breast cancer. KIRSTEN BEYER: Thank you, Dr. Westin. Yes, redlining-- I think most people think about redlining as being a historical practice, where mortgage lenders would essentially draw red lines around particular neighborhoods and then not lend mortgages in those areas, regardless of whether or not the applicant for that mortgage was otherwise qualified. So it's generally thought of as a historical practice. But what we've done in this study is to look at some more contemporary data and create a new measure that we think represents contemporary redlining, maybe not in the legal sense in terms of housing discrimination. But this measure represents essentially the odds ratio of denial of a mortgage application for a property in a local neighborhood as compared to the metropolitan area as a whole. So we're really looking to see which areas of our US cities are systematically denied mortgage applications. By denying those mortgage applications, they are suffering from disinvestment, and I would argue structural racism is guiding a lot of that practice. SHANNON WESTIN: So can you explore that a little bit more with us? And how do you find that type of data? Where do you get this information about these denied mortgages? How do you get into the different covariates like race, ethnicity, things like that? KIRSTEN BEYER: Sure. So I think a little history lesson is important first. Between the historic practice of redlining and today, there have been a number of major laws that have been passed in the United States really to try to overcome housing discrimination. Some of the most important ones are-- in the Civil Rights Act of 1968, there was something called the Fair Housing Act, and that act prohibited discrimination in the sale, rental, and financing of housing based on race, religion, and national origin. And since then, they've added a few more protected categories. And then right after the Civil Rights Act of 1968, there was something passed called the Home Mortgage Disclosure Act. And this act was essentially to bring transparency to mortgage lending in this country. The idea was that we were requiring public disclosure of loan-level information about mortgages that were lent in the country. And the goal was to shed light on lending patterns, including those that could be discriminatory. And so the HMDA data-- it's commonly referred to as "hum-duh." That HMDA data has been collected then since 1975. And that database evolves over time, but we use that data for 2007 to '13 to really try to understand what are the mortgage lending patterns in our US cities in terms of their spatial distribution. And so there are a number of covariates that we were able to control for there. There are some things that we're not able to control for. I'm excited that the HMDA database has recently improved, and there are some new variables that are going to become available in the coming years. So what we did with the HMDA database was to calculate an index of redlining, so an odds ratio of denial of a mortgage application for a property in a specific neighborhood compared to all the properties across the metropolitan area. And so it's an area-level measure, a neighborhood-level measure. And then we put that measure into a statistical model to see what happens to women diagnosed with breast cancer if they live in redlined areas compared to if they live in other areas. And so we were able to control for a number of other factors, including race, including tumor characteristics, age, stage at diagnosis, and then to see what is the added effect of redlining over and above the things that we already know impact survival. So what we found was that women living in redlined areas in the United States were more likely to die faster after breast cancer diagnosis than women living in other areas. We also found that among people living in redlined areas, there was a discrepancy in terms of the race and ethnicity of those women. So 79% of Black women, 57% of Hispanic women, and 34% of white women lived in redlined areas in our sample. SHANNON WESTIN: That's so interesting, because I think we've all read and seen across a number of different cancer types how race and ethnicity can be associated with worse outcomes. So I think you're starting to scratch the surface of why that might be. Now, do we think that is there an association with other factors like socioeconomic status or insurance or anything like that? KIRSTEN BEYER: Yes, I think those are really good questions. Not all databases contain all of the information we would like. But in SEER-Medicare, which is the database we use, we know that all of the women have health insurance because it's a linked database with cancer registry data and then Medicare claims data. So health insurance wasn't a factor here, but we certainly know that it could be a factor in a larger sample of women across the age spectrum. And I think when you get into questions of socioeconomic status, you also have to think about, as opposed to statistically controlling away the effect of socioeconomic status, what is the mediating effect? Or what is the explanation? What factors explain the relationship between redlining and breast cancer survival? So I think that's where we'll see a lot of the important explanations for how does redlining contribute to survival. SHANNON WESTIN: Thank you. I think you nailed it right there, because finding a problem is, of course, important, but then what do we do next? Dr. Griggs, I thought your editorial was just so great at providing context for this issue, and I was wondering if you could expand a little bit more on this idea around residential segregation and how it impacts outcomes for these patients. JENNIFER GRIGGS: Thank you very much, and thanks for including me on this great podcast. It's so important to understand that place matters more than race, and we've known this for quite a while. So that area-level factors are associated with environment-- for example, pollutants, safe water, safe places to play, safe places to exercise, transportation fragility, for example, a robust public transport system. We know that neighborhoods that are in redlined areas are more likely to be policed in different ways, which takes children from school being suspended at higher rates. There's less educational investment, but Dr. Beyer mentioned this disinvestment in neighborhoods basically has shutters all the way down. It shutters from childhood all the way to how we age and access to healthy food. We know redlined areas are associated with poor markers of diabetes control, and if you take somebody from an area that's a poor neighborhood that's segregated and give them a voucher to live in a more affluent area, that markers of diabetes improve and weight goes down. So just to think about this, that the impact of where we live affects things that we think of as personal behavior-- like, what we eat or how we control our diabetes. There are, of course, implications for access to high-quality health centers when we think about people sort of locked into certain neighborhoods, all that goes along with that, including wealth. Wealth is probably one of the biggest predictors of health and not being able to have the wealth associated with home ownership decreases economic stability. And we know these things like allostatic load or stress, sometimes called wear-and-tear effects, are associated with things like tumor biology and breast cancer. We see more triple-negative breast cancers in areas where there's more allostatic load. So imagine, we think about race as this fixed-- sometimes people even construe race as a biologic construct, when really, of course, it's a social construct that has systematically-- our systems have been put in place so that even the legislation, Fair Housing Act, can't be overcome, as shown in Doctor Beyer and colleague's paper. In other words, despite legislation, we continue to see mortgage lending bias, which we've termed contemporary redlining. Yet, we think of race as this fixed, deterministic way of describing people and explaining differences and outcome. So this kind of work is really important when we can show the effect of place independent of race and if we can show that there has been systematic construction of something so important as residential segregation. What this does is it drives us to really a call to action. A lot of ideas in there, but basically, showing where people live being associated with their outcome in breast cancer-- and this has been shown in other cancers, as well-- through pathways like economic stability and wealth, wear and tear on the body, and then to acknowledge the sad truth that things have been intentionally constructed structures. SHANNON WESTIN: I mean, I think this is really in line with a lot of what we're learning about our society and our country, the way we were educated when we were younger was that we did not always hear the truth about what really went down as this country was built. I think that you really touched on a lot of very critical points. And I think for me, a lot of times when we read about these racial and ethnic disparities, I feel like it often comes down to where people are like, oh well, it's just access to care, or lack of insurance, or they're just not focusing on these things. They're not educated. They don't know that these things are important. But what I hear the two of you saying is, it goes much deeper than that. So Dr. Beyer, I'd be interested to hear your thoughts on that with these areas. Should we be working on improving what is available to people in these areas? Or should we work on breaking down or both? KIRSTEN BEYER: Yeah, thanks, Dr. Westin. That's a great question, and it's a complicated one. I think Dr. Griggs mentioned housing vouchers. And so for example, when we are giving someone a housing voucher to move from a more vulnerable neighborhood, let's call it, to a less vulnerable neighborhood, that can improve health outcomes for sure. But we also know that there's a downside to that. Sometimes there are impacts on social support or mental health. And then on the flip side, if we are trying to improve neighborhoods themselves so that the people living in them can benefit from those enhancements, we often see that what happens is gentrification, when people who are living in those neighborhoods get displaced, and newer people, wealthier people, move in and take those amenities. So I think it's something that really requires close management with housing policy. And then I think another thing that I would add is that, as you mentioned, we're really scratching the surface. I think that's an important thing to emphasize. This is one aspect of housing. There are other aspects that are very important, like quality of housing and stability of housing, which is what Dr. Griggs mentioned. And I think it's also important to note that even if a person is denied a mortgage application because of a credit score, that credit scores, wealth, income, and many other things that are considered in the mortgage lending process are also affected by structural racism, as are things like home appraisals, mentorship, and eviction, something that we've certainly seen during the COVID-19 pandemic. SHANNON WESTIN: Wow, so thoughtful. I feel like I'm trying to take notes as fast as I can because I'm learning so much. I think we didn't hear about anything like this in our medical school and your PhD training. I don't know if you all got any type of background in this. Dr. Griggs, did you-- I mean, we never even scratched the surface with the impact of structural racism. And in fact, I think a lot of our medical education was founded in that structural racism. JENNIFER GRIGGS: I couldn't agree more, and I couldn't agree more with what Dr. Beyer said about things like housing vouchers, so I just want to acknowledge that it's not as simple as giving people a voucher, obviously. No, we are calling for structural competence. There are multiple calls that we teach medical students and current practicing clinicians and scientists the structures that have been put into place and that persist. So again, that intentionality that these systems were put in place through deliberate efforts, and it's only going to be through deliberate efforts that they're dismantled. And teaching people that individual behaviors are not predetermined or, frankly, learned. They cross multiple generations, and they reside within a place and the way not just a person, but an entire people, have been treated. And I do just want to say, although this may be new to a lot of us, that the lived experience of people who live in vulnerable neighborhoods and their life experience and their family's experience going back many generations make this not new news, right? This is old news. This is stuff people have known for generations that they're being systematically cut out of opportunities for advancement and for accumulation of wealth. So I think we just want to be-- I just want to be careful when I'm talking with my colleagues, my team, my research colleagues that this is not new knowledge. And we want to also be careful not to be parasites in a way on other people's suffering, that we want to be careful not to glorify our own ideas because number one, they're not our ideas. And number two, this type of work is the lived experience of people for many, many years, not just our neighbors and friends and colleagues. So there's so much harm that's been done, and we can celebrate advances and new knowledge, but I also think we want to focus on cultural humility and do a lot of deep listening and less talking and build trusting relationships with communities that are not about our career advancement but are really about fairness and justice. SHANNON WESTIN: I think that needs to be shouted from the rooftops, and I think it is a very careful balance, because we want this research to get out. We want to make sure people understand this. You're right. It's not new knowledge, but I think it's something that hasn't necessarily been highlighted in academic fields up until, like, the last few years, where I feel like we've started to see this. But you're exactly right. We can't just do the research and find the association. Now it's time for the next steps. And I'd be interested to hear from both of you, because, to me, there are several levels of steps that we can take. There's the local level, right? So what can we do for the patients in front of us? And then I'd be interested to hear what you all think about what do we do on the more institutional-- and by institutional, I mean, our entire country. Like, what can we do? How do we advocate for policies that will help to reverse these practices? I don't know Dr. Beyer, if you want to start. I know that was a really big question. What can we do when we're seeing patients in the clinic? Are there ways, or are there things we can offer or things that we can do on the local level that could help to address some of these disparities? KIRSTEN BEYER: Yeah, thank you, Dr. Westin. I'm not a medical doctor, but I work a lot with medical students. We have some pathways at the Medical College of Wisconsin, one on urban and community health and one on global health. And in those pathways, we do try to put forth a lot of this type of content and learning. But again, that's just a select number of students who end up getting that training. I think that structural racism is a fundamental force in our society, and therefore, it justifies a position in the core medical curriculum. I think since the murder of George Floyd, there has been a national consciousness that's been raised around this issue, that we should take advantage of that and try to push forward some core learning on structural racism for medical students. And then beyond that, I think as a patient, I can use the patient perspective. As a patient, I would want my physician to take into account my life context when providing clinical care. How hard is it for me to get to my appointment and to get there on time? How hard is it for me to find child care? How hard is it for me to obtain the prescriptions I need and maintain them with any significant cost at hand? So I think that awareness for physicians is really a first step. And then the last thing I would say is that doctors have power, and so I think it's the responsibility of those with power who are in the know about structural racism to leverage and use that power to make social change. JENNIFER GRIGGS: I really appreciate what you said from education to practice. I would add that an integrated health system would be able to think from prevention all the way up to health care. I feel like by the time people are accessing health care, a lot of other things have gotten in the way of their health, right? That's why we talk about social determinants of health. So I think we need to think about elevating the role of other people in the health care system. So even if you're in an individual practice, do you have access to a social worker? Are you including patient and family voices when you build your new office? We have transportation initiatives being made all over this country, and I know in Europe as well. So cities are being designed to undo transportation fragility and vulnerable neighborhoods. I can't emphasize enough the importance of asking communities what they need. It strikes me that the ivory tower is just that, right? It's very rarefied where we work. And to go into a community and say, this is what you need, feels-- which is not what you were suggesting, Dr. Beyer or Dr. Westin, but to start by listening and ask the communities what they need and then to provide it and to listen and not leave once the, quote, "problem is fixed." And I think the same is true nationally. We need to make sure that the administration's priorities actually bear fruit and soon, that we not kick things down the road and make compromises at the level of national policy. And as physician clinicians, those physicians who are listening, we should be going to the city council meetings when a new building is being erected. Is there going to be a consequence for neighborhoods in terms of things like gentrification? Cities have been constructed intentionally to isolate people, and we need to start undoing that, and cities are doing that. They're taking down freeways that divide the rich from the poor. I think we need to make sure as clinicians that we are speaking up about equitable and high-quality education for young people because we know your early life experiences and education are associated with health. Publishing work like Dr. Beyer's work, ASCO has a heavy advocacy arm. And as Dr. Beyer said, we have power. Inequities in power is what got us to where we are. So really, the burden is on those with power to speak on Capitol Hill and other places, local level, statewide level, to make change and to insist on it for the health of our patients and our communities. SHANNON WESTIN: That is so thoughtful and such a great call to action. And I do think there's a huge opportunity for members of ASCO to get involved. The advocacy is extremely strong. There are Capitol Hill days and committees, and now we even have their own political action committee, where we can work to lobby for patients and their health care. So I think that is a perfect place for us to end this conversation. I would like to give Dr. Beyer last opportunity to one-liner to sum up where we are and what we need to do next for those people that tend to fade in and out of these types of things. KIRSTEN BEYER: Sure. Thank you, Dr. Westin. I would say, to summarize, that the housing sector is actively revealing structural racism. This isn't a historic practice only. We are seeing structural racism in housing right now, and it's actively revealing both structural racism and economic disinvestment. And it's a very actionable policy target, so that we can mitigate those upstream determinants of health for the benefit of patients with cancer and with other diseases. And then I think as a final, I would say that there's a great quote from Matthew Desmond, who's a housing equity writer and scholar and activist. And he says, "A stable home functions as a secure foundation on which to build holistic and cost-effective health care." And so I think that's a great way of thinking about it from a practical standpoint. Housing is primary. It's an important foundation on which we build all the other things that we can do to improve people's health. SHANNON WESTIN: Perfect. Thank you both so much. Thank you, Dr. Beyer. Thank you, Dr. Griggs. And thank you, all of the listeners. We'll be back soon with a new podcast coming to a ear near you. JENNIFER GRIGGS: Thank you so much. KIRSTEN BEYER: Yeah, thank you very much. [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.

ASCO eLearning Weekly Podcasts
Oncology, Etc. - On Leadership and Pearls of Life with Dr. Susan Desmond-Hellmann (Part 2)

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Nov 18, 2021 20:10


In the second part of this Oncology, Etc. episode Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas) continue their conversation with Dr. Susan Desmond-Hellmann, exploring the prominent leadership roles she held, from first female Chancellor at UCSF to CEO of the Bill and Melinda Gates Foundation and member of Facebook's Board of Directors. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/18/21   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. PAT LOEHRER: Hi, Everybody. I'm Pat Loehrer. I'm director of the Centers of Global Health at Indiana University, Melvin and Bren Simon Comprehensive Cancer Center. DAVE JOHNSON: And I'm Dave Johnson. I'm Professor of Medicine here at UT Southwestern Medical School in Dallas, Texas. So Pat, we're back for another episode of the award winning "Oncology Et Cetera." PAT LOEHRER: Just seems like last month we were here time, you know? Time just flies. DAVE JOHNSON: Exactly. Before we get started, you were telling me about an interesting book you were reading-- something about friends or something. Can you elaborate? PAT LOEHRER: Sure, sure, yeah. This book I picked up-- actually, my wife picked it up. It's called First Friends. It's written by Gary Ginsburg. It's a really interesting book. It was-- basically talks about-- it probably has about eight or nine presidents but the importance of having a friend that guides him. And these were people that were, in many ways, unelected people that were close to the presidents that helped change the face of what we see today, and some of them are stories of really good friends and some of them are, I think, opportunistic friends. But it gives you a background of people like Madison and Lincoln and Roosevelt and Woodrow Wilson. It's actually a fun read. DAVE JOHNSON: I'll definitely put it on my reading list. It sounds like a pretty exciting one. Well, speaking of influential people, we're really excited to jump back into our interview with Dr. Helman. In our last episode, we covered her early life and career, her work in Uganda, her views on global oncology, and her experiences in private practice and industry. In the next half of our interview, we'll learn more about her incredible career and her multiple leadership roles. Let's start by hearing about her time as chancellor of UCSF. PAT LOEHRER: Let me transition a little bit. What I'd like to do is talk a little bit about your leadership. One Of the next big roles you had, you became chancellor at UCSF, correct? SPEAKER 2: Mm-hm. PAT LOEHRER: And so as Dave said, I think you were the first woman in that role. SPEAKER 2: I was. PAT LOEHRER: You were a groundbreaker from that capacity. So now instead of working for people-- obviously, I understand that there's people you work for when you're chancellor too, but tell a little bit about that transition from industry back into academics and how that felt in the role of being a leader and then maybe the responsibility of being the first female chancellor. SPEAKER 2: There were parts of being the chancellor at UCSF, I would say most parts of it, that I just thought were fantastic. I loved being back at a hospital and clinics. Just the way the hospital and clinical enterprise at UCSF works, the chancellor is the board. And so once a month, you'd have neurology or cardiology come and tell you about what had happened, quality control, things that had gone on and I would have done that all day long. I mean, it was just so interesting. It was so important to run a great clinical enterprise that getting back closer to patients and medicine I thought was fantastic. The other thing was the educational enterprise, and UCSF, as you know, has medicine, pharmacy, dentistry, nursing. I always tell people, no undergraduates, no English majors, no marching band. And the other chancellors reminded me, no athletic director, which apparently is a very good thing. So UCSF is a very special and unusual place. And I loved the science. I would show up at research seminars and things like that as often as I could. So there were so many parts of being at UCSF that I thought were just off the charts great. The hardest thing about being at UCSF-- being the first female chancellor, I think, was challenging but not in ways that you might expect. I was used to being a woman leader in medicine and biotech, which was unusual. So being the only woman in the room, being the first, wasn't new to me. But the thing that was hard on our family was there are roles for the spouse of the chancellor that fit more neatly into more of a classic female role, hosting things. There was a tea party for the wives of the faculty that the wife of the chancellor typically had. And for some reason, Nick didn't think that that suited him. We sort of laughed about that. DAVE JOHNSON: He can't make tea? SPEAKER 2: He can't make tea to save his life. And he's a strong introvert, which made it worse. I will tell you, some of the under-recognized, underreported people in life are spouses of chancellors and presidents of universities. And talk about unpaid labor-- my goodness! And so we sort of struggled with how did Nick show up, what did that look like. Because we didn't have any role models for what that looked like. I still laugh that Bill Clinton said he would be First Laddie. So when you have a pattern recognition, life is easier. And then being one of 10 chancellors at the UC system, I struggled a little bit with the UC Regents just because it felt-- I became chancellor in 2009, and we had some fiscal realities that we were dealing with. And the pace of the UC Regents and the format of the UC Regents, I actually made a proposal for UCSF to kind of break off from the other 9. And that was not well-received, got me in the newspaper. And I did not do that again. People saw it as disloyal and not very smart. But all in all, I thought then and think now that our public universities are absolutely-- they're treasures in America. And I was really proud to be a part of it and hope that I had made a contribution. DAVE JOHNSON: Speaking of leadership, what was it like to be CEO of the Bill and Melinda Gates Foundation? What caused you to step away from chancellor to philanthropy? PAT LOEHRER: It's not a step down. It's not a step down, basically. DAVE JOHNSON: It is not a step down. SPEAKER 2: So I would say a couple of things. First of all, Bill and Melinda pushed me hard to take the job. I was not looking to change. My husband worked at the Gates Foundation for a couple of years on HIV. So they knew us, and they knew Nick better than me. But they knew both of us. We awarded Melinda the University medal at UCSF. And to my great surprise and happiness, she accepted and came. I later think that she was using that as a reason to talk to me about the CEO job, but she got a twofer. And I was really compelled by the mission. Who wouldn't be? I was really compelled by the mission and the chance to get back into global health after the experience I had had in Uganda. But I'll tell you, it is the ambition of the Gate Foundation, the scope of the Gates Foundation, the resources, and the need to get something done. I tell you, it is hard work. It is really hard work-- from China to India to all of the continent of Africa and then US education. Throw that in on top of things. So I was thrilled to be a part of driving the agenda and the mission. Some really talented people who are working very hard at the Gates Foundation-- I was surprised, especially on US education, with the amount of pushback. And I worked really hard to be successful at working with Bill, who's known as a tough character and lived up to that mutation. DAVE JOHNSON: Good to know, just in case he calls Pat or me. PAT LOEHRER: Yeah, yeah, I'm not going to get a medal at UCSF either. So that's a-- DAVE JOHNSON: You never know, Pat. PAT LOEHRER: It's a non-starter. And this may not apply to you, but there's a lot of maybe disproportionate number of women who feel they suffer from this imposter syndrome. To be honest, Dave and I have talked about that. We both feel in that syndrome too. But along the way, I mean, if you think about growing up in Reno, Nevada, and suddenly now being a chancellor and head of the Gates Foundation, the National Academy of Science, was there ever this sense of the, wait a minute, you know, what's going on? Is this real? SPEAKER 2: For me, there has always been that sense. There has always been that sense, and I look at it as I hope there always will be that sense-- that the kind of need to demonstrate your value. And there's a part of the imposter syndrome that is humility and not overestimating what you can do. And so on my best days, I think that leads me to say I've got to work with really terrific people. My job is to bring out the best in others. If I lead, it's because there's a great thing we're going to accomplish, and I can help people see where we're going together. And so I definitely have had imposter syndrome. But the one thing that I probably overused and kind of grew to like too much was the thing of people underestimating me and then proving them wrong. That gets a little wearying after a while. It's like, OK, we're going to waste some time while you decide whether I'm worthy or whether I can do this. And let's not waste that time. Why don't you assign to me-- give me some confidence, and I'll live up to that. And I mentioned Art Levinson was my boss for most of the time I was at Genentech. And he had no time for imposter syndrome. He was like, look, how many promotions do you have to get before you think, OK, I can get this done? He thought that was sort of-- he just didn't have time for it. We have things to do, and he had jobs to get done. And one of the things I loved about him is he would constantly push me to say, you're capable of more than you think you are, which I think is the sign of a fantastic manager, which he was and is. And so I've tried to push myself to do that. And the thing is, like, you can do this. Come to me for help. We'll make sure you succeed, but don't underestimate yourself. And I think that's a consequence of imposter syndrome is both wasting time proving yourself and not taking on something that you think, actually, let me give that a try and stack the deck in favor of succeeding. And so I think that's the thing that-- there's a certain fierceness that I've always had that I like about myself that, like, of course we will succeed. Failure is not an option. Of course we will succeed. And I think that comes from working on things that I value a lot and care about a lot. PAT LOEHRER: You have been on a number of different boards, including Pfizer as well as Facebook. And in that capacity, you've seen a lot of leaders. Can you talk a little bit about the strengths and the weakness of various leaders as well as serving on the boards and the capacities of the different companies? SPEAKER 2: Yeah, well, first, let me say I know ASCO is actually a really good about being careful about conflicts of interest and things like that, and I am too. So when I became chancellor at UCSF and then CEO at the Gates Foundation, I avoided being on life sciences boards. And so I got asked a lot by Biotech and pharma boards to be on their boards. Initially, I joined Procter Gamble's board, where I served for, I think, about six years. And then I joined Facebook's board. And those were both fantastic experiences. And I actually joined the boards for two very different reasons. One, P&G's board, I wanted to learn about branding and consumers. And I felt like in medicine, I didn't really learn about consumers or branding as much as I needed to or might. And then Facebook's board I joined because as Dave mentioned, I was with Charles Sawyers. We wrote the precision medicine report for the National Academy. And I really love-- to this day, I love the concept of using the social network to connect people. There was sort of an infamous story or famous story-- it's actually a good story-- of patients with a certain form of myeloma who found each other on Facebook and went to Genentech and said, make a new medicine for those of us with this genetic abnormality. And we'll all enroll in a trial. And so these connections to me felt really powerful on precision medicine. And so getting to work with CEOs at Procter and Gamble, the CEO Mark Zuckerberg at Facebook, I do see the really different attributes of leaders. But when you're a board member, you see those attributes of leaders with a very different lens. What's the return to shareholders? How does the community think about them? What's the impact-- and increasingly for Facebook, what's the impact on the world? What's the impact on our social discourse and our ability to have a free and fair election? A lot of those things became much more operative on the Facebook board while I was on the board and really tough social issues that continue to this day. DAVE JOHNSON: Yeah, so we could go on for another hour, hour and a half, but I have one question to ask you which may seem a little bit silly in retrospect. But if you could look back on your youthful self at 21 or 22 knowing what you know now, with all the things that you've done during the course of your career, what advice would you give yourself? And perhaps I'll addend that by saying what advice would you give particularly to young women in the medical profession who are trying to balance that work-life balance that everyone talks about and worries about and struggles with, quite frankly. SPEAKER 2: I'll give you one thing I should have done better and one thing that I think I did well. So the advice on the one thing I should have done better, I think slow down a little bit and take a bit more time for fun and enjoyment. I was extremely worried about money when I was in college, and being number two of seven-- every summer, I worked. I remember at one point in medical school, I had three weeks off, and I got a job for those three weeks at a deli making sandwiches. And I went to college for three years, crammed it into three years so I wouldn't have to pay for the fourth year. So I just think that I could have taken on more loans. I could have done some things to just dial it down a bit because you don't get those years back. And that's such a great time of your life when you're 21, 22, something like that. So I wish I'd have just slowed down a bit and not been so driven for those seven years of university and medical school that I really just either worked or studied all the time. The thing that I feel like I did well, and I would say this to anybody who's going into medicine, is there's so many opportunities. There's so many wonderful things to do. But whoever your spouse is, whoever your partner in life is, take the time and energy to make sure that's the right person for you. I feel so blessed. Actually, my husband, who I've mentioned several times in this discussion, Nick, was my roommate in San Francisco when I was an intern, like real roommate. And we've been roommates ever since. And we're very compatible. He's one of seven kids too. It's another Catholic school kid. And we just have fun together and support each other. And there's no way I could have taken these crazy jobs or done the kinds of things I've done without Nick. So having a wonderful, supportive partner makes everything better. DAVE JOHNSON: That definitely resonates with Pat and me. We're both very blessed to have wives and spouses of, for me, it's 52 years. I can't remember, Pat. Yours is close. PAT LOEHRER: I had my first date with my wife 50 years ago, yeah. DAVE JOHNSON: Yeah. SPEAKER 2: OK, so you guys know what I'm talking about. PAT LOEHRER: Absolutely. DAVE JOHNSON: Yeah. PAT LOEHRER: Yeah. DAVE JOHNSON: Go ahead, Pat. PAT LOEHRER: I was going to ask a question that you probably may have already answered there, but Bob Woodward just came out of an interview with Colin Powell. One of the last questions he asked him was if he could reflect on that one person that was a moral compass for him. And so for you, that one person, alive or dead, that has been not the most powerful person you've met but the one that's really influenced you the most in terms of giving you direction, who would that be for you? SPEAKER 2: Probably, if I look at through line the entire time I've been alive, it would be my dad. He had the ability to look at a room and find the person who was struggling and go over to them. And I really loved that about my dad. PAT LOEHRER: I love it. DAVE JOHNSON: One last question. So we're at the top of the hour, and I know you're a very busy person. Pat and I love to read, but we're also documentary fiends and whatnot. We're interested. What have you read recently that really resonated with you? Do you have a recommendation for us? SPEAKER 2: I will say during the pandemic, I've gotten back into reading biographies, which I love. DAVE JOHNSON: Yeah. SPEAKER 2: So I did the Caro, Lyndon Baines Johnson, which, Master of the Senate is really good. But my favorite book of the last two years is The Code Breaker, Walter Isaacson's book about Jennifer Doudna. DAVE JOHNSON: Yeah. SPEAKER 2: One of the things I love about Walter Isaacson is he teaches you science through his biographies. Like, I think I understand relativity based on his Einstein biography, which is great. But The Code Breaker is really super good. DAVE JOHNSON: Yeah, we both read it. We couldn't agree with you more. PAT LOEHRER: Love it. Love it. DAVE JOHNSON: So Sue, again, it's been a real honor to have you as our guest, and we really appreciate the time you've taken. Thank you so much, and we hope you enjoy the beautiful weather in Alamo California, and I hope it does turn green and the rain continues for you. SPEAKER 2: Thank you so much. It's been my pleasure. Thank you both. DAVE JOHNSON: Take care. SPEAKER 2: Bye. DAVE JOHNSON: I want to take the moment to thank our listeners for tuning in to "Oncology Et Cetera," an ASCO educational podcast where Pat and I really will talk about anything and everything. So if you have an idea or a topic you'd like to share with us and like for us to pursue, please email us at education@asco.org. Thanks again, and keep in mind that Pat is a giant in oncology, but he's a short instructor. Thanks, everybody. SPEAKER 1: Thank you for listening to this week's-- to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

ASCO Daily News
Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC

ASCO Daily News

Play Episode Listen Later Nov 18, 2021 12:52


Guest host Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah Huntsman Cancer Institute, interviews Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, on the practice-changing VISION trial and its impact on the current treatment paradigm for mCRPC. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC       ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC       ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

ASCO Guidelines Podcast Series
Considerations for the Use of Steroids: Management of irAEs Guideline (Part 13)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 16, 2021 8:58


An interview with Dr. Leslie Fecher from the University of Michigan Health System, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews considerations for the use of steroids to manage immune-related adverse events in patients treated with immune checkpoint inhibitor therapy in the final episode of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune related adverse events. I am joined by Dr. Leslie Fecher from the University of Michigan Health System in Ann Arbor, Michigan, author on "Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy. ASCO Guideline Update" and "Management of Immune Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T Cell Therapy, ASCO Guideline." And today we're focusing on considerations for the use of steroids to manage immune related adverse events in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Fecher. LESLIE FECHER: Thank you, Brittany, for this invitation. BRITTANY HARVEY: Great. Then I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guidelines in the Journal of Clinical Oncology. Dr. Fecher, do you have any relevant disclosures that are related to these guidelines? LESLIE FECHER: The details of my disclosures are included in the manuscript, but I'd just like to note that I have received research funding, specifically in the form of clinical trial funding, from companies that do manufacture these immunotherapies. BRITTANY HARVEY: Thank you. Then getting into the content, so steroids are valuable agents in the management of immunotherapy related adverse events. So first, what should clinicians consider pretreatment with steroids? LESLIE FECHER: So I think one of the first things is obviously going back to the traditional history and physical exam, and making sure you understand any preexisting comorbid conditions, such as diabetes, high blood pressure, preexisting cataracts or glaucoma, infections, osteopenia or osteoporosis. It's always good to try and optimize things before getting started on steroids. Additionally, it's typically considered very reasonable to check hepatitis B and C serologies prior to starting immunotherapy treatment. And also consideration of assessment for tuberculosis, if there are specific risk factors, understanding if somebody already carries a diagnosis of HIV, and Understanding the status of that in advanced would be relevant. BRITTANY HARVEY: Those are important considerations. Then in addition to that, how should opportunistic infections be prevented? LESLIE FECHER: So one of the most common infections that we tend to try and prevent is pneumocystis jirovecii pneumonia, or PJP, previously known as PCP pneumonia. And this is one of the more common things that we recommend prevention for. So in patients who have received the equivalent of prednisone dosing of 20 milligrams per day for four or more weeks, or greater than 30 milligrams per day for three weeks or more, that's when it would reasonably be indicated. There are obviously specific institutional guidelines for the preferred regimen, but I think that's important to consider. The role of viral prophylaxis as well as antifungal prophylaxis is a bit less clear, but is something to be considered, especially depending on the duration of the steroid course. And whether or not in the setting of herpes zoster, for example, if the patient has had issues with zoster in the past. BRITTANY HARVEY: OK. and then the use of these steroids is to treat immunotherapy related adverse events. But what are the key recommendations for monitoring both the short term and long term adverse effects from steroids? LESLIE FECHER: So I think being aware of the side effects as well as making sure that the patients and the family members or loved ones that are helping them are aware of them as well. From a short term standpoint, typically we recommend things such as GI prophylaxis, with either a proton pump inhibitor or a histamine 2 antagonist, to reduce or prevent gastric ulcers or duodenal ulcers or gastritis. Given some of the long term effects, such as bone loss as well as steroid myopathies, we encourage exercise as well as physical therapy in some circumstances. But really one of the most important things is to make sure that you're constantly both assessing and eliciting from the patient and family members for any other side effects. So often, common acute short term side effects can be increased risk of infection. So making sure you're asking about it. They may not have the typical manifestations of infection, such as fevers or chills. Insomnia or difficulty with anxiety, irritability, skin changes for sure, or high blood pressure. And then obviously being aware that laboratory evaluation for glucose intolerance is important as well. BRITTANY HARVEY: Definitely. Those are important points for clinicians, patients, and caregivers. So then we've had some of the other authors on this guideline talk about tapering steroids. So what are those recommendations on how clinicians should taper steroids? LESLIE FECHER: So tapering is an art in and of itself in my opinion, and there's lots of different ways to do it. Some general concepts are you want to really try and understand what the side effect is that you are managing, because that will require frequent reassessment. And so when we talk about reassessing patients during the treatment of their toxicities, the management of the toxicities, in my opinion, is almost as important as the management of the immunotherapy itself. And so patients still need to be seen, still need to be assessed, still need blood work done. And so reassessment for the toxicity that you're managing, given that we can see rebounding of symptoms. So for example, if they were getting treated for diarrhea or colitis, having a really good understanding of what their baseline bowel movements were, how bad they got, and then a constant reassessment and making sure that the patient, as well as the family, knows that this should not come back again, if you will, in the midst of the taper. I think the other things to be aware of is that I tend to always reassess before giving the next decrease in dose of the steroids rather than having an automatic decrease. Because again, patients sometimes will follow those, even if their symptoms recur. So ensuring that there's that, again, reassessment. When we're on oral steroids, some of the general concepts we say is that the course should be at least usually about four weeks total, sometimes as long as six weeks or even longer, depending on the toxicity. And we think about, on average, decreasing from a prednisone or prednisolone amount roughly 10 milligrams every three to seven days, depending on the side effect that you're managing. The longer the taper, the slower you might need to go, depending at the end. And also being aware of the risk of adrenal insufficiency towards the end of a long steroid course is also an important thing to assess for. BRITTANY HARVEY: Great. I appreciate you reviewing those considerations. So then in your view, Dr. Fecher, how will these recommendations for the use of steroids in the management of immune related adverse effects impact both clinicians and patients? LESLIE FECHER: I think it will bring ongoing awareness to the physician and their team, as well as the patient and their team. I think that this is obviously really important that everybody is involved and aware. And I use the term engagement from a patient and family member standpoint. It's really critical to have an understanding of the side effects, have an understanding of the prednisone management. And explaining that not only to the physician team and nurses and other people involved in their care, but when patients call in, that they know to look out for rebounding of their symptoms and to report them immediately, as that can impact steroid tapering. I think, again, the awareness and engagement is going to ensure that patients get the best care and best results. BRITTANY HARVEY: Absolutely, and thanks for highlighting both that awareness and engagement. So thank you so much for your work on these guidelines, and for taking the time to speak with me today, Dr. Fecher. LESLIE FECHER: Thank you so much, Brittany. I appreciate your time. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

ASCO eLearning Weekly Podcasts
Cancer Topics - New Therapies for Lymphoma (Part 2)

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Nov 15, 2021 20:48


In the second part of this ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of new therapies for mantle cell lymphoma and follicular lymphoma through examination of challenging patient cases. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/15/21

ASCO Guidelines Podcast Series
Ocular Toxicities: Management of irAEs Guideline (Part 12)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 15, 2021 6:39


An interview with Dr. Marc Ernstoff from the National Cancer Institute, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” He reviews identification, evaluation & management of ocular toxicities in patients receiving ICPis, including uveitis, iritis, and episcleritis in Part 12 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune related adverse events. I am joined by Dr. Marc Ernstoff from the National Cancer Institute in Bethesda, Maryland, author on "Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update" and "Management of Immune Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T Cell Therapy, ASCO Guideline." And today we're focusing on ocular toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Ernstoff. MARC ERNSTOFF: Thank you, Brittany. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Ernstoff, do you have any relevant disclosures that are directly related to this guideline? MARC ERNSTOFF: I have no further disclosures at this time. SPEAKER 1: Great. Thank you. Then let's get into these ocular toxicities. So first, what are the immune related ocular toxicities addressed in this guideline? MARC ERNSTOFF: So the ocular toxicity is addressed in the guidelines represent a relatively uncommon side effect of immune checkpoint inhibition, and represents inflammation of all components of the eye from the superficial component to the internal uveal component. So there is iritis. There's episcleritis and uveitis, are the ones that are usually identified by physical examination and by complaints. BRITTANY HARVEY: Understood. Then so let's start with what are the key recommendations for identification, evaluation, and management of uveitis and iritis. MARC ERNSTOFF: So those are excellent questions. I think that it's important for clinicians to recognize that while most of the eye toxicities are relatively minor, low grade, and can be managed effectively, there are some that are very important to identify, particularly as they may lead to blindness, particularly uveitis or pan uveitis. So identification of these symptoms and signs are important. So evaluation of the patient by asking whether there are any eye symptoms-- dryness or irritation-- is important in your evaluation of the patient's side effects. In addition, looking at the eye, both with a penlight, looking for any inflammatory signs, and doing a ophthalmologic examination to make sure there's no cloudiness or anything identified in the retina is important. BRITTANY HARVEY: Great. And then furthermore, what are the key recommendations for identification, evaluation, and management of episcleritis? MARC ERNSTOFF: So episcleritis can usually be seen by irritation in the superficial areas of the eye. Usually if it's low grade, it can be managed with topical steroids and continuation of the immune checkpoint inhibitor. On the other hand, if it's more bothersome and not responding to topical therapy, evaluation by an ophthalmologist, potentially interruption of immune checkpoint inhibitor, is important. And if it's severe, systemic steroids might be required at that time. BRITTANY HARVEY: Great. Thank you for reviewing how to best identify and manage that particular toxicity. So then in your view, how will these recommendations for the management of ocular toxicities impact both clinicians and patients? MARC ERNSTOFF: So again, I think it's important that both from symptom management, that these, many times, can be managed with topical steroids and tears effectively, and that a patient's therapy can continue, which I believe is important. On the other hand, identifying areas that may be beyond the expertise of an oncologist, would require evaluation by an ophthalmologist, including a slit light examination. It is important to recognize that uveitis can have minimal symptoms and yet be more severe in its condition, requiring intervention and holding of immune checkpoint. And if really severe-- grade 3 or 4-- the interruption and discontinuation of immune checkpoint inhibition is probably going to be required to manage the side effect. Again, if undiagnosed and untreated, it can lead to blindness. So while not quote life-threatening, clearly a major impact in quality of life of a patient that is preventable, if identified. BRITTANY HARVEY: Great. Thank you so much for viewing these recommendations for the management of ocular toxicities, to ensure both the quality of life of patients and the best practices for management of these toxicities. So I want to thank you for your work on these guidelines and for taking the time to speak to you today, Dr. Ernstoff. MARC ERNSTOFF: Thank, you very much, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

1001Tracklists Exclusive Mixes
ASCO - LIVE @ 1001Tracklists x ROCKI Present: Top 101 Producers 2021 ADE Celebration

1001Tracklists Exclusive Mixes

Play Episode Listen Later Nov 15, 2021 21:34


ASCO - LIVE from 1001Tracklists x ROCKI Present: Top 101 Producers 2021 ADE Celebration!

A vivir que son dos días
La píldora de Tallón | Sentir asco es buenísimo

A vivir que son dos días

Play Episode Listen Later Nov 14, 2021 3:19


"Llega siempre un momento en el que alguien quiere convencerte de que hacer solo lo que te gusta es un plan de vida poco realista". 

ASCO Guidelines Podcast Series
Cardiovascular Toxicities: Management of irAEs Guideline (Part 11)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 12, 2021 12:27


An interview with Dr. Pauline Funchain from Cleveland Clinic, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews the recommendations for cardiovascular toxicities in patients receiving ICPis, including overall cardiac toxicities (i.e., myocarditis, pericarditis & arrhythmias), and VTE in Part 11 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune related adverse events. I am joined by Dr. Pauline Fontaine from the Cleveland Clinic in Cleveland, Ohio, author on "Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update," and Management of Immune Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T Cell Therapy, ASCO Guideline." And today we're focusing on the cardiovascular toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Fontaine. PAULINE FONTAINE: Thank you, Brittany, for the invitation. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines, and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Fontaine, do you have any relevant disclosures that are directly related to these guidelines? PAULINE FONTAINE: So I do. My institution receives research funding from Pfizer and Bristol Myers Squibb for clinical trials where I'm a primary investigator. And I have done some consultation work with Eisai. BRITTANY HARVEY: OK. thank you for those disclosures. Then talking about the content of this guideline, what are the immune related cardiovascular toxicities addressed in this guideline? PAULINE FONTAINE: So there are two major categories. One is an overall cardiovascular category. That includes myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis. That's overall. And there's a second category of venous thromboembolism. BRITTANY HARVEY: Great. Then starting with that overall category, what are the key recommendations for identification, evaluation, and management of myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis? PAULINE FONTAINE: So in that overall category, I think it's important to recognize that there are symptoms that are a little bit more general. They may be cardiovascular. They may be pulmonary. But we have to be aware that some of these can be cardiovascular. So that would include worsening fatigue, progressive or acute dyspnea. I think they're generally going to be other things, but you really have to recognize a potential cardiac IRE, as those can have major medical consequences. I mean there are other things that are more obviously cardiac, like chest pain, arrhythmia, palpitations, acute onset peripheral edema. And it is important to note that they can, like every other IRE, happen at any time. In the literature, the median time to onset is 6 weeks, but the range is somewhere between 1.4 to 54, and we know that it can be all over the place with IREs in terms of presentation. Then next would be evaluation. So with evaluation, whenever you see this type of side effect, fatigue, dyspnea, chest pain, it's natural to want to get an EKG troponin. I think that's a great place to start. And I think if there's more concern for cardiac type of IRE, then an echocardiogram, a chest X-ray, I think, are probably the next easiest evaluations to assess for cardiac IRE. One of the important things to note is that cardiac IREs, especially myocarditis, tend to happen along with concurrent myocytis, so it's important to check a CPK to rule that in or rule that out. And typically, then if people need more evaluation, the cardiac MRI is the next step, but things like cardiac catheterization may be involved. And so that's where I think it's really important with management to have cardiology involved early. I mentioned this briefly before, but it's really important to know that myocarditis has a very high fatality rate, up to about 50% in published series. I think as we get better at recognizing myocarditis, that fatality rate will likely go down, but catching a cardiac IRE late can have some very serious implications for our patients. So immediately recognizing that a cardiac workup is necessary, and referring early to cardiology is really important, no matter what grade of cardiac IRE we see. And I do think that with cardiac IREs, it's really, is it an inpatient workup? Does it require immediate cardiac consultation and workup? If there are elevated troponins that are going up, or conduction abnormalities, does that patient need to be in a cardiac unit? I think those are the major things to keep in mind with management. Another thing, I think, that is really important because of the high fatality rate: starting corticosteroids early. So like our other IREs, you can start corticosteroids that 1 to 2 mgs per kg per day. And doing that early has the potential to quickly improve cardiac inflammation, keep people from the very serious and potentially fatal side effects for cardiac IREs. And it really doesn't have that much of a consequence in the short term. So I think in discussions about this guideline, we all felt that if a patient has a Grade 2 or higher IRE-- so that's anything that has a cardiac biomarker that's abnormal plus symptoms of any kind-- it's important to keep in mind early steroids and early cardiac consultation. For very, very severe cases where management with corticosteroids is not improving the patient's status, then we highly recommend considering cardiac transplant rejection doses, which would be methyl pred at 1 gram daily, or adding other immunosuppressants. So there are not as many studies as we would like, but mycophenolate, infliximab, antithymocyte globulin have all been reported. There have also been case reports on abatacept or alemtuzumab, with good outcomes. So those are things to consider, of course, with cardiology input for severe cases. BRITTANY HARVEY: Thank you. Those are important notes for clinicians to keep in mind for management and evaluation. So then, the second category that you mentioned, what are the key recommendations for identification, evaluation, and management of venous thromboembolism? PAULINE FONTAINE: So for identification, most everyone listening to this podcast knows what a venous thromboembolism looks like. That's extremity swelling, extremity pain, sometimes accompanied by fever, pleuritic pain, cough, dyspnea. And the evaluation is the same as what you would see in clinic. That would be venous ultrasounds for any suspected deep vein thromboembolisms. And CT, PE for any suspected pulmonary embolism. And of course, a VQ scan if you can't do that type of CT. And the management is the same as what you would normally do in clinic. So if it's a superficial thrombosis, that would be a grade 1. You would do a warm compress, do supportive care. But importantly, you can continue the immune checkpoint inhibitor per our recommendations. For grade 2, so a symptomatic thrombosis, a deep vein thrombosis, that would require anticoagulation. But again, once anticoagulation has been started, the recommendation is that it is safe to continue the immune checkpoint inhibitor therapy, because at this point, you're protected. Should be, in theory, protected from future embolic events. And then, I think the major thing is that for management in general once there is anticoagulation on board, then there isn't necessarily a reason to hold immune checkpoint inhibitor therapy. I think that the major reasons we would recommend to hold it are life threatening consequences, organ damage. So grade 4 embolic event, where you would have to admit the patient. And then it becomes a risk benefit discussion after an admission. In general, I think the recognition and treatment are the same in terms of venous thromboemboli that are identified in the context of immune checkpoint inhibitor therapy. The major thing is just to know that it exists as a potential side effect, that the incidences appear to be higher, and that there is something about immune checkpoint inhibitor therapy that may put our patients at higher risk for these embolic events. BRITTANY HARVEY: Definitely. That's key to know, and particularly also when to hold or continue ICPI therapy. So then in your view, Dr. Fontaine, how will these recommendations for management of cardiovascular toxicities impact both clinicians and patients? PAULINE FONTAINE: I think the major thing is to know that these exist. The overall cardiac toxicities are less common, so if we're talking about myocarditis, that is a pretty rare event. But it's important to know that this is an event that is potentially fatal, that that fatality happens often, and that myocarditis can occur along with a myositis, and in some cases with myasthenia gravis. So these are three different rare side effects that can happen together, sometimes in pairs, sometimes in triplets, sometimes just one of them. But any one of these three has a higher risk for fatality. So I think just to know that it's out there. So that that is just hanging around in the differential for someone who is tired or out of breath. It may be pulmonary, but also keep in mind that it could be cardiac, and that is serious, and that should be worked up early and treated early. I think that's the major thing that I hope these guidelines do, is put these important but rare side effects out there and potentially save lives. I will say for VTEs, for venous thromboemboli, again, so PE can happen, and it can be fatal. I think this is not as rare, but of course, it's not rare in our patient population either. So these are things that we already look out for. Just, I think, if this podcast and the guidelines can add to the education that immune checkpoint inhibitors will increase the risk of thromboembolism, I think that those are the important takeaways. BRITTANY HARVEY: Absolutely. Recognition of these IREs is a common theme across the affected organ sites that we've heard in many of these podcast episodes. So I want to thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Fontaine. PAULINE FONTAINE: Thank you for having me. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

ASCO Guidelines Podcast Series
Hematologic Toxicities: Management of irAEs Guideline (Part 10)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 11, 2021 18:34


An interview with Dr. Loretta Nastoupil from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of hematologic toxicities in patients receiving ICPis, including hemolytic anemia among others in Part 10 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Loretta Nastoupil from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update, and Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy ASCO Guideline. And today, we're focusing on hematologic toxicities in patients treated with immune-checkpoint inhibitor therapy. Thank you for being here, Dr. Nastoupil. LORETTA NASTOUPIL: Thanks, Brittany. I'm happy to be here. BRITTANY HARVEY: Great. Then first I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Nastoupil, do you have any relevant disclosures that are related to these guidelines? LORETTA NASTOUPIL: Yes, Brittany. So I have received honorarium for participation in advisory boards from the following companies, including BMS/Celgene, Genentech, Janssen, Novartis, Merck, MorphoSys TG Therapeutics, and Takeda. And I've also received research funding support from BMS/Celgene, Gilead Kite, Genentech, Janssen, Novartis and Takeda. BRITTANY HARVEY: I thank you for those disclosures. Then let's get into what we're here today to talk about. So what are the immune-related hematologic toxicities addressed in this guideline? LORETTA NASTOUPIL: So it's important to recognize that hematologic toxicities that are immune-related as a result of immune therapy are infrequent occurrences. So it's important to recognize when they do occur and some of the unique workups given that they are so infrequent. So probably one of the most common is hemolytic anemia. It's important to recognize that these are cancer patients. And they may have multiple reasons for the development of acute or new onset anemia, but recognizing if they're on either checkpoint inhibitors or immune therapies, it's important to recognize that it might be spurred on as a result of immune-mediated anemia. We advise in terms of history and workup to consider whether or not they've been exposed to new drugs, whether or not they've had a recent insect or snakebite exposure. The recommended workup includes a CBC with also a peripheral blood smear to look for evidence of hemolysis or macroketosis. In addition, other hemolytic anemia workup includes evaluation for LDH, haptoglobin, reticulocyte count, bilirubin, and free hemoglobin. Other potential diagnoses on the differential include DIC, so a panel, including coags, PT, INR, and PTT, exploring autoimmune serologies, PNH screening, evaluation for infection such as viral or bacterial causes of hemolysis, and also consideration for bone marrow failure syndrome, including evaluation for potentially reversible causes, such as B12, folate, copper, parvovirus, iron, thyroid, infection, et cetera. G6PD level is helpful in the evaluation, as well as exploration as I mentioned of potentially new drugs that might be linked, including ribavirin, rifampin, dapsone, interferon, some of the antibiotics, such as cephalosporins, penicillins, NSAIDs, ciprofloxacin, for instance, et cetera. So as part of the workup, if we have excluded alternative causes and we think that the immune-checkpoint inhibitor might be the underlying cause of the autoimmune hemolytic anemia, then generally we will continue unless they have grade 2 or higher toxicity, which is generally a hemoglobin less than 10. In which case, we would recommend to hold the immune-checkpoint inhibitor, again, with significant anemia. So those with grade 2 or higher, you might consider initiating corticosteroids, including 1.5 to 1 milligram per kilogram per day until improvement. For grade 3 or higher-- so this is more severe anemia So hemoglobin is less than 8. Generally, we're recommending permanent discontinuation of the checkpoint inhibitor and potentially higher doses, including up to 2 milligrams per kilogram per day of prednisone or corticosteroid equivalent to speed up the recovery. In regards to transfusion requirements or consideration, we are suggesting you evaluate or consider your local or regional guidelines. We generally do not transfuse for a target hemoglobin greater than seven to eight. And we also recommend supplementation with folic acid. BRITTANY HARVEY: Great. And then beyond those recommendations for hemolytic anemia, what are the key recommendations for identification, evaluation, and management of acquired thrombotic thrombocytopenia purpura? LORETTA NASTOUPIL: Sure. So fortunately, TTP is quite rare, but, again, something that is worth exploring. Some of the challenges are in the clinical syndrome. And that it can mimic some of the other toxicities that are covered in other sections, particularly the neurotoxicity section. But essentially, for patients who have pretty dramatic change in platelet count, again, they may have additional clinical sequelae such as neurologic toxicity or adverse events. It's important to recognize that TTP might be an underlying cause, again, for patients who are on immune-checkpoint inhibitors. This is where a hematology consult early in the clinical course would be particularly of importance to recognize it and potentially to minimize offending agents. Drug exposure is always important, because many of these patients might have other drugs, in addition to their immune-checkpoint inhibitors, such as chemotherapy, sirolimus, tacrolimus, antibiotics et cetera. And so exploring offending agents is important. An ADAMTS13 level, an inhibitor titer, would be important to send if you're considering TTP, in addition to evaluating the peripheral smear, and the hemolytic anemia workup, as I just mentioned, including LDH, haptoglobin and reticulocyte count. Exploring infectious etiology, including CMV titers or serology, would be particularly helpful, an additional clinical evaluation, such as brain imaging with CT or MRI, echocardiogram, and EKG would be of help. For all grades of TTP, again, even with a clinical suspicion for the diagnosis, in addition to hematology consult, we recommend stabilizing the patient. That might require care in an acute care setting, making sure that they have adequate organ function and that this is stabilized. For grade 1 or higher, we recommend holding the immune-checkpoint inhibitor. And you might consider, again, initiation of corticosteroids with 0.5 to 1 milligram per kilogram per day of prednisone or an equivalent. For grade 3 or higher, we would, again, in addition to holding the checkpoint inhibitor and in conjunction with your hematology colleagues, you might initiate a therapeutic plasma exchange. Again, in accordance with existing guidelines, you may consider higher doses of steroids, including methylprednisolone 1 gram IV daily for three days. You could consider some additional supportive agents, such as rituximab or pembrolizumab if the ADAMTS13 level is less than 10 or less than 10% of normal and an inhibitor or elevated ADAMTS13 IgG has been detected. BRITTANY HARVEY: I appreciate you going through the details for TTP. So then, additionally, this guideline addresses aplastic anemia. So what are the key recommendations for identification, evaluation, and management of aplastic anemia? LORETTA NASTOUPIL: Yeah. So fortunately, again, these are quite rare situations. So with aplastic anemia, similar to what we've discussed in terms of workup of anemia, globally, it's important to explore potentially causes of, again, bone marrow failure syndrome. And aplastic anemia is one of those such causes. Exploration of a bone marrow biopsy in conjunction, again, with your hematology consult would be critically important, and exploring potentially reversible causes, again, such as deficiencies and important nutrients, viral etiologies, in addition to parvovirus, CMV, HHV-6 is important to consider and rule out. But I think the end of the day, a bone marrow biopsy and aspirate is going to be the most helpful assessment to ensure that aplastic anemia has been considered and worked up. In regards to management of aplastic anemia, we're going to hold the immune-checkpoint inhibitor. You may need to provide additional support such as growth factors. And close follow-up, I think is the most critical aspect of this. Sometimes we initiate patients on corticosteroids. We hold the checkpoint inhibitor. And then we may monitor them less frequently. Oftentimes, these patients with high malignancies are going to need to be followed very closely, sometimes weekly or multiple times a week. So in regards to management of aplastic anemia that might be immune mediated as a result of immune-checkpoint inhibitors and in conjunction with your hematology and colleagues, consideration of management might include administration of horse ATG and cyclosporine, but again transfusion support, growth factor support, even consideration for HLA typing and evaluation first. Stem cell transplantation might be appropriate, particularly for a young patient with minimal comorbidities. For grade 3 or higher, in addition to these considerations, we're going to hold the checkpoint inhibitor and monitor weekly for improvement. If no response, you might consider repeating immune suppression with Rabbit ATG plus cyclosporine or cyclophosphamide. And for refractory patients, consider eltrombopag plus best supportive care. BRITTANY HARVEY: Great. Thank you. Those are important notes on the management of aplastic anemia. So then, additionally, what are the key recommendations for the identification, evaluation, and management of lymphopenia? LORETTA NASTOUPIL: Yeah. I think one of the challenges with lymphopenia, it's common for patients who've had cancer-directed therapy, particularly things like chemotherapy. And so understanding whether or not this is a new onset after exposure to checkpoint inhibitors is one of the critical aspects, in addition to considering alternative causes. But for patients in which we do think the lymphopenia is a result of the immune-checkpoint inhibitor, we're not generally advising discontinuation or holding of the immune-checkpoint inhibitor, but it is important to consider best supportive measures, including whether or not patients might benefit from monitoring for reactivation of certain viral etiologies, including CMV and HHV-6, for instance, in addition to potential consideration for prophylactic strategies, such as PJP prophylaxis. Also, zoster reactivation might be something that these patients might indeed be at risk for. So as opposed to holding your checkpoint inhibitor and initiating things like corticosteroids, if we have excluded alternative causes and think lymphopenia is a result of the immune-checkpoint inhibitor or as immune mediated, ensuring that they are receiving best supportive care to mitigate some of their toxicity that may result as the result of the lymphopenia. BRITTANY HARVEY: Understood. And it's important to note for clinicians that management is different from a lot of the management of the other hematologic toxicities. So then the last hematologic toxicity that was addressed in this guideline was acquired hemophilia A. So what are those key recommendations? LORETTA NASTOUPIL: Acquired hemophilia A, again, fortunately is very rare and uncommon, but this is one situation where engagement of a hematologist, who is an expert in management of hemophilia, will be critical. So that would potentially be step one. In terms of laboratory assessment, that would be helpful, in addition to your CBC, where you're assessing things like platelet count, coagulation workup, including fibrinogen, PT, PTT, INR, that would be informative. Patients with acquired hemophilia A will likely have a prolonged activated PTT with a normal PT. So that might be one of the clues. Imaging would be helpful to ensure the patients don't have any signs of spontaneous bleeding or hematoma basis, such as MRI, CT, or ultrasound, if particularly they have any localizing symptoms. Medication review to look for alternative causes would always be helpful. And determination of the Bethesda unit level of inhibitor would be critical. In regards to management, we would hold the checkpoint inhibitor, initiate corticosteroids, transfusion support as indicated, and you want to treat the underlying acquired hemophilia with conjunction of a hematologist. For grade 2 or higher, this may require factor replacement. And the choice is usually based on the Bethesda unit of the titer. Administration of prednisone, in addition to rituximab 375 milligrams per meter squared weekly for four weeks or cyclophosphamide dosed at 1 to 2 milligrams per kilogram per day may be patient specific. And, again, that decision should be made in conjunction with your hematology consult. Prednisone, rituximab, and cyclophosphamide should be given for a minimum of five weeks. And factors should be prescribed to increase the level, particularly during bleeding episodes. And, again, the choice of the factor is based on the presence or absence of an inhibitor. For grade 3 or higher, we advise to permanently discontinue the immune-checkpoint inhibitor. These patients generally will be admitted for stabilization. They do require factor replacement. Bypassing agents may also be required, including factor VII. Caution should be taken in elderly patients and those with coronary artery disease. Corticosteroids, rituximab, and cyclophosphamide should also be considered, transfusion support, if they're having active bleeding. And if worsening or no improvement, you could consider adding cyclosporine or immune suppression to try and stabilize these patients. Again, acquired hemophilia A requires special clinical and laboratory expertise. This would require consult and potentially even transfer to a specialized center, and consultation with a hemophilia center should be initiated as soon as this is considered or confirmed. BRITTANY HARVEY: That's a great summary of these recommendations. The expert panel and you clearly put in a lot of work into these recommendations. So then in your view, how will these recommendations for the management of hematologic toxicities impact both clinicians and patients? LORETTA NASTOUPIL: I think the most important thing are disseminating this information. I think ASCO plays a critical role in helping clinicians first recognize some of the toxicities that are different from what we have traditionally seen with chemotherapy and may have different management strategies. So guidelines, such as this, are critically helpful. Podcasts, such as this, are incredibly helpful to get the information out, recognizing that all of us authors are more than willing to provide additional guidance and are willing to be contacted in this situation where someone's facing one of these unique and rare toxicities and would like some additional guidance in terms of further management. Hematologic toxicities are sometimes hard to distinguish or maybe potentially hard to recognize, given many of these patients may have been on prior chemotherapy agents, and anemia or thrombocytopenia may not be unusual, but recognizing if it's new or more severe than what has been seen previously and that, at least, consideration of an immune-mediated hematologic toxicity, be considered, because the management might be unique. And so I hope that we've outlined today some of the hematologic toxicities that are rare that may be seen with immune therapy and some of the strategies to work up alternative diagnoses and management if it is indeed immune-mediated toxicity. BRITTANY HARVEY: Definitely. And I really appreciate you going through these rare but very important toxicities. So thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Nastoupil. LORETTA NASTOUPIL: Thanks, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.ASCO.org/supportive care guidlines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Nervous System Toxicities: Management of irAEs Guideline (Part 9)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 10, 2021 20:11


An interview with Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews neurologic toxicities in patients receiving ICPis, such as myasthenia gravis, Guillain-Barre Syndrome, peripheral neuropathy, aseptic meningitis & encephalitis in Part 9 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune related adverse events. I am joined by Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center in New York, New York, author on Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy ASCO Guideline Update and Management of Immune Related Adverse Events in patients Treated with Chimeric Antigen Receptor T Cell Therapy ASCO Guideline. And today, we're focusing on nervous system toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Santomasso. BIANCA SANTOMASSO: Thank you for having me. BRITTANY HARVEY: Then I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Santomasso, do you have any relevant disclosures that are directly related to these guidelines? BIANCA SANTOMASSO: Yes, I'd like to disclose that I've served as a paid consultant for Celgene, Janssen Pharmaceutical, and Legend Biotech for advising them on the topics of T cell therapy side effects. BRITTANY HARVEY: Thank you. Then getting into the content of this guideline, what are the immune related nervous system toxicities addressed in this guideline? And what are the overarching recommendations for evaluation of these neurologic immune related adverse events? BIANCA SANTOMASSO: So neurologic immune related adverse events actually encompass a very diverse spectrum of neurologic syndromes that can occur as a complication of treatment with checkpoint inhibitors. So the spectrum that is covered by this guideline includes myasthenia gravis, Guillain-Barre syndrome, polyneuropathy, aseptic meningitis, and encephalitis. And although these are rarer than many of the other immune related adverse event types affecting other organ systems, they're increasingly being encountered due to more patients being treated with novel combinations of immunotherapies. And they're important to recognize, because along with myocarditis, they have generally more morbidity and even more mortality than irAEs affecting other organ systems. So it's important for clinical care providers to have a high index of suspicion for these events. Studies have suggested that these tend to occur in about 3% to 12% of patients, probably between 1% and 2% of patients developing severe events. So they're rare. But again, the events are probably more commonly seen in patients treated with combination checkpoint blockade. And we're increasingly seeing more combinations. So we should be on the lookout for these. Neurologic immune related adverse events can be divided into syndromes that affect the peripheral nervous system, so meaning the peripheral nerves, the neuromuscular junction, and muscle. So that would be Guillain-Barre syndrome, myasthenia gravis, and myositis. And those that affect the central nervous system, such as the brain, spinal cord, or leptomeninges. So those would be aseptic meningitis and encephalitis. The peripheral nervous system irAE appear to be more common than those affecting the central nervous system. And patients can present with a number of different symptoms that kind of relate to these syndromes. That can be as diverse as a headache to numbness, tingling, or focal weakness, such as a foot drop or facial weakness. You may see patients with severe altered mental status or personality changes or gait difficulty, walking difficulty, which could actually mean any number of syndromes. It's generally important to be aware that the timing of onset is generally early, a median of four weeks after the start of treatment, but can range anywhere from one week after the start of treatment to greater than a year. And because we know that cancer can spread to many parts of the nervous system, neurologic toxicity should be considered a diagnosis of exclusion. So that means that as part of the workup for neurologic immune related adverse events, it's imperative to rule out nervous system metastasis, stroke, and infection, which we know can occur at higher rates in patients with cancer. So for most neurologic immune related adverse events, diagnostic workup is similar. It should include MRI brain and/or of the spine, with and without contrast, and often a lumbar puncture for cerebrospinal fluid analysis, including cytology to rule out leptomeningeal metastasis. BRITTANY HARVEY: Thank you for that overview. In addition to those points for evaluation for all nervous system toxicities, what are the key recommendations for identification, evaluation, and management of myasthenia gravis? BIANCA SANTOMASSO: So for myasthenia gravis, presenting symptoms usually include fatiguable or fluctuating muscle weakness. It's generally more proximal than distal. And there's frequently ocular and/or bulbar involvement. So that means either ptosis, like a droopy eyelid, diplopia, or double vision, difficulty swallowing, dysarthria, facial muscle weakness, and/or head drop or neck weakness. Again, for any patient with new neurologic symptoms, an MRI of the brain or spine should be performed depending upon the symptoms to rule out central nervous system involvement by disease or some alternative diagnosis. And similar to idiopathic myasthenia gravis, acetylcholine receptor antibodies can be positive. So these should be checked. This is a blood test. But it's important to note that while these antibodies may be confirmatory, their absence does not rule out the syndrome. The rate of acetylcholine receptor antibody positivity in immune related myasthenia gravis has not been definitively established. So depending on the presentation, one might also consider sending a paraneoplastic panel for Lambert-Eaton myasthenic syndrome. The single most important point I'd like to make regarding suspected immune related myasthenia gravis is that orbital myositis and generalized myositis from immune checkpoint inhibitors can present similarly. For this reason, early neurology consultation and electrodiagnostic testing with repetitive stimulation or single fiber EMG becomes important and helpful to distinguish the two. And to make matters even more complicated, we've learned that there's an overlap syndrome, where patients may develop not only myasthenia gravis, but also myositis and/or myocarditis at the same time. So basically, the neuromuscular junction is affected. But the local muscle and myocardium, which is heart muscle that's kind of related, may be affected all at once. And this overlap of syndromes may increase disease severity and mortality. So they're important to recognize. So what this means is that when you encounter a patient with suspected myasthenia gravis, you should also be checking CPK, muscle enzymes, aldolase to evaluate for myositis, and troponin and electrocardiogram to evaluate for myocarditis. And this should be done even if there are no obvious symptoms. So onto the treatment of myasthenia gravis, this is similar to the management of the idiopathic form. Therefore, it's helpful to have the involvement of a neurologist. The immune checkpoint inhibitor therapy should be held. And patients with mild symptoms are often started on pyridostigmine and corticosteroids. And patients with more severe symptoms should initiate IVIG or plasmapheresis. And patients with more severe symptoms may need to be admitted to the hospital. So that their neurologic and pulmonary status can be monitored closely for improvement. Some patients may require ICU level of monitoring. And considering adding rituximab if symptoms are refractory, and often, as symptoms improve, the steroids can be de-escalated. BRITTANY HARVEY: Understood. Those are all very important points for clinicians to consider. So then following that, what are the key recommendations for identification, evaluation, and management of Guillain-Barre syndrome? BIANCA SANTOMASSO: So Guillain-Barre syndrome, like myasthenia gravis, also presents with weakness. Most often, patients present with a progressive ascending muscle weakness. The syndrome can start with sensory symptoms or neuropathic pain that can be localized to the lower back and thighs. In addition to the classic ascending weakness, there may be facial weakness, double vision, numbness or tingling in the hands or feet, loss of balance, and coordination. And shortness of breath may occur due to respiratory muscle weakness. The autonomic nerves can also be affected and can present as new severe constipation or nausea, urinary problems, or orthostatic hypotension. The reflexes are often reduced or absent, deep tendon reflexes. So again, as for all of the syndromes, early involvement by a neurologist is recommended, if possible. Usually, MRI imaging of the spine is important to rule out spinal cord compression. And it also may show cauda nerve thickening or enhancement, which can occur with this syndrome. And the second aspect is cerebrospinal fluid analysis is important for diagnosis. This is important really for ruling out leptomeningeal metastasis, since that could present similarly. And often, what can be seen in GBS is an elevated protein level in the cerebrospinal fluid. In addition, unlike idiopathic GBS, there can be an elevated white blood cell count in the cerebrospinal fluid. Electrode diagnostic testing can also be helpful for confirmation, and serum tests for antiganglioside antibodies, and a paraneoplastic antibody workup may also be considered. Bedside pulmonary function test and swallowing evaluation should be performed if there's a concern for respiratory or swallowing dysfunction. And some patients do need to have inpatient admission and monitoring if symptoms are severe or if they appear to be progressing from mild. For management, the checkpoint inhibitor therapy should be held. And patients are most often treated with IVIG or plasmapheresis. Corticosteroids can be added to the IVIG or plasmapheresis. These are not usually recommended for idiopathic Guillain-Barre syndrome. However, in immune checkpoint inhibitor related forms, a trial is reasonable. And steroids are usually given at a higher dose for five days and then tapered over several weeks. BRITTANY HARVEY: Understood. I appreciate that overview. So then what are the key recommendations for identification, evaluation, and management of peripheral neuropathy? BIANCA SANTOMASSO: So peripheral neuropathy, or polyneuropathy, is a rare but likely underreported complication of immune checkpoint inhibitor therapy. So in the large databases and meta-analyses, those have really focused on Guillain-Barre syndrome for reporting. But other types of neuropathies, such as painful length dependent sensory and motor axonal neuropathies, or polyradiculopathies or sensory neuropathies do occur after immune checkpoint inhibitors and are probably under-recognized. So evaluation of immune related neuropathy should include neurology consultation to guide the neurology phenotype determination and also the workup. The evaluation primarily relies on a combination of electrodiagnostic studies, serologic tests, and MRI neuroimaging. Because peripheral nervous syndromes can overlap, screening for neuromuscular junction dysfunction with electrodiagnostic testing and myopathy is recommended for any patient who presents with at least motor symptoms that are thought to be peripheral. Serum testing can be helpful for ruling out reversible causes of neuropathy. Spinal imaging is recommended to exclude metastatic disease. And for management, it usually involves holding the checkpoint inhibitor in mild cases, using neuropathic pain medication or steroids in more severe cases. And very severe cases that kind of resembled GBS would be managed as per the GBS algorithm with IVIG or plasmapheresis. BRITTANY HARVEY: Understood. And it's key to look out for those overlapping adverse events. So then following that, what are the key recommendations for aseptic meningitis? BIANCA SANTOMASSO: Right, so now we're getting into the central nervous system toxicity. So aseptic meningitis is an inflammation of the meninges. And it can present with headache, photophobia, neck stiffness. Patients can have nausea, and vomiting, and occasionally fever. The mental status is usually normal. And in patients presenting with headache, which in isolation, could suggest an aseptic meningitis, it's important to evaluate if they have any confusion or altered behavior, which might suggest an encephalitis. And this distinction is important, because suspected encephalitis triggers a different workup, which we'll be discussing later, and also even different management. So the workup for aseptic meningitis includes neuroimaging, usually an MRI of the brain. And on that imaging, we sometimes see abnormal leptomeningeal enhancement. It's important not to assume that this is cancer and to do a lumbar puncture to evaluate cerebrospinal fluid both for inflammation and to exclude other causes of meningeal disease, particularly neoplastic and infectious causes. So cytology, Gram stain, and culture, and other infectious studies should be negative. And it's recommended that empiric antibiotics or antiviral therapy be considered to cover for infectious meningitis until the cerebrospinal fluid results return negative. What's seen in the cerebrospinal fluid in aseptic meningitis is typically reactive lymphocytes, but also neutrophils or histiocytes may be prominent on the cytology. And while the symptoms can be severe, sometimes requiring hospitalization, the management of this entity, these are usually quite treatable. Aseptic meningitis generally responds very well to corticosteroids. So management involves holding the checkpoint inhibitor. And you can often get away with starting a fairly modest dose of corticosteroids, such as oral prednisone, 0.5 to 1 milligram per kilogram or the equivalent. And steroids can usually be tapered over two to four weeks. BRITTANY HARVEY: Great, thank you for reviewing those recommendations. So then you just mentioned the distinction of aseptic meningitis and encephalitis. So what are those key recommendations for identification, evaluation, and management of encephalitis? BIANCA SANTOMASSO: So in encephalitis, the mental status is not normal. It's characterized by, really, an acute or subacute confusion, altered mental status, altered behavior, memory deficits, including working memory and short-term memory. There can be, as associated symptoms, headaches, new onset seizures, psychiatric symptoms, which can include delusions or hallucinations. There could be weakness, sensory changes, imbalance, or gait instability, along with the mental status changes. And so similar to aseptic meningitis, the other central nervous system toxicity, it's important to distinguish encephalitis from other causes of altered mental status, such as CNS metastases, stroke, or infection. And as for the other syndromes, it's very helpful to have neurologic consultation early, if possible. An MRI of the brain is critical. And in addition, MRI of the spine may be obtained to evaluate for inflammatory demyelinating ischemic or metastatic lesions. In immune related encephalitis, MRI brain imaging may reveal T2 flare changes, typical of what can be seen in idiopathic autoimmune or limbic encephalitis. But most often, the MRI imaging is normal. So in this situation, a lumbar puncture for CSF studies to evaluate for evidence of inflammation can be very helpful. You can expect to see either a lymphocytic pleocytosis or an elevated protein, or CSF restricted oligoclonal bands. CSF analysis is also helpful for excluding other causes of encephalitis, particularly viral encephalitis. So HSV, Herpes Simplex Virus, or varicella zoster virus encephalitis should be ruled out and treated with antivirals while the tests are pending. So typically, these entities can be excluded by PCR testing for HSV and VZV. Electroencephalogram, or EEG, can also be helpful for revealing subclinical seizures or status epilepticus, which can occur as a complication of encephalitis or as a cause of persistently depressed sensorium. But these are not specific to encephalitis. Other testing that's done includes screening metabolic tests to look for alternative etiologies. And for this entity, serum and CSF autoimmune antibody evaluation should be sent to assess for malignancy associated neurologic syndromes. And your neurologist can help you with the workup and management, in particular which tests to send. There have been reported cases of antibody positive checkpoint inhibitor related encephalitis. For management, in contrast to aseptic meningitis, these are generally not as steroid sensitive. So you often have to treat with either higher steroid doses, even pulsed steroid doses, along with IVIG or plasmapheresis. If no improvement, escalation to rituximab and cyclophosphamide can be considered, with the assistance of neurology. This management guidance is taken from how to treat autoimmune encephalitities that are not related to checkpoint inhibitors. Unfortunately, these can be difficult to treat. The response may only be partial. So this is one area in need of better understanding of best therapeutics. BRITTANY HARVEY: OK, thank you for reviewing that and pointing out where there's future research needed as well. And I appreciate your reviewing the recommendations for each of these neurologic immune related adverse events. So then to wrap us up, in your view, how will these recommendations for the management of nervous system toxicities impact both clinicians and patients? BIANCA SANTOMASSO: Yeah, so I think this is a daunting list of toxicities. But I'll say that in most situations, the immune checkpoint inhibitor side effects are often manageable and reversible with proper supportive care. They can be serious, and they require close vigilance and prompt treatment and identification. But by knowing what to look for in early identification, that allows early intervention, which is really the key to reversibility and the best outcomes. So having these toxicities on your differential diagnosis is critical. And I think these guidelines really help inform both clinicians, and care providers, and patients on what the possible manifestations are. So we believe this guideline and its recommendations will help members of clinical teams with the recognition and the management of these unique toxicities. And again, it's timely recognition and early intervention that helps patients, really, by increasing their safety with early management. BRITTANY HARVEY: Great, well, thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Santomasso. BIANCA SANTOMASSO: My pleasure. Thank you so much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe. So you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Renal Toxicities: Management of irAEs Guideline (Part 8)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 9, 2021 10:47


An interview with Dr. Umang Swami from the Huntsman Cancer Institute, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” He discusses the identification, evaluation, and management of renal toxicities in patients receiving ICPis, focusing on nephritis/acute kidney injury in Part 8 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune related adverse events. I am joined by Dr. Umang Swami from the Huntsman Cancer Institute at the University of Utah in Salt Lake City, Utah, author on Management of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy ASCO guideline update, and Management of Immune Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T Cell Therapy ASCO guideline. And today, we're focusing on renal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Swami. UMANG SWAMI: Thank you, Brittany. And I appreciate the invitation to be here today. BRITTANY HARVEY: Great. Then first, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Swami, do you have any relevant disclosures that are directly related to these guidelines? UMANG SWAMI: No, I do not have any relevant disclosures that are directly related to these guidelines. BRITTANY HARVEY: Thank you. Then let's dive into what we're here today to talk about. So what are these immune related renal toxicities that are addressed in this guideline? UMANG SWAMI: So this guideline focuses on nephritis, or acute kidney injury, as an adverse event due to immunotherapy. Acute kidney injury, or AKI, an uncommon complication of immune checkpoint inhibitor therapy. Just to give a little context before we start, the incidence of any grade AKI around 1% to 2% in patients treated with a single agent immune checkpoint inhibitor, such as ipilimumab, nivolumab or pembrolizumab, and 4.5% in those treated with anti-CTLA-4 for and anti-PD-1 combination of nivolumab plus ipilimumab therapy. The incidence of grade 3 or grade 4 AKI is very low. I will say less than 1% with single agents, and around 1.6% with the combination of nivolumab plus ipilimumab. While initial studies had quoted a small incidence of AKI with immune checkpoint inhibitor use, emerging data now suggests that a higher incidence might be present, which might range between 9.9% to around 29% of AKI with the immune checkpoint inhibitors. However, most of this extra toxicity is grade 1. The median time to onset of renal toxicity with these agents is around 14 weeks, but can range from 6.5 to 21 weeks. BRITTANY HARVEY: Thank you for that background information. I think it's helpful for clinicians to understand how rare or common these adverse events are. So then, what are the key recommendations for identification, evaluation, and management of nephritis or acute kidney injury? UMANG SWAMI: That's a great question. Presenting symptoms related to immune therapy induced renal toxicities may include urinary frequency, dark, cloudy urine, fluid retention, or edema of face, abdomen, extremities. There might be sudden weight gain. There might be associated abdominal or pelvic pain. Patients might have nausea, vomiting, high blood pressure, or they may have a change in mental status such as drowsiness. However, we should remember that a vast majority of them will be asymptomatic at presentation. Therefore, patients should have their renal function, that is, serum creatinine, checked prior to administration of each dose of checkpoint inhibitor therapy. For patients with new elevations in creatinine, one should consider holding checkpoint inhibitor therapy while other potential causes are evaluated. These other causes may include recent IV radiographic contrast administration, dehydration, urinary tract infection, other natural toxic medications, including concurrent chemotherapy, herbals, or other supplements. Patients without their obvious causes or who don't respond to alternative treatment measures should be presumed to have immune related renal toxicity and treated empirically depending on the grade of AKI. Safe treatment of autoimmune component is important. So with regards to the grading of AKI, grade 1 means a creatinine level increase of more than 0.3 milligrams per deciliter, or creatinine 1.5 to two times above baseline. And in this situation, physicians should consider temporarily holding checkpoint inhibitor therapy and evaluating other potential contributing agents in combination regimes, pending consideration of potential alternative pathologies. A change that is still less than 1.5 times of upper limit of normal could be meaningful and should be remembered. For grade 2 AKI, which is creatinine two to three times above baseline, apart from holding immune checkpoint inhibitor and evaluating for alternative causes, nephrology should be consulted. If other ideologies are ruled out, administer 0.5 to 1 milligram per kg per day prednisone or its equivalent. If kidney function worsens or does not improve after one week, increase the dose of prednisone to 1 to 2 milligrams per kg per day or its equivalent, and permanently discontinue immune checkpoint inhibitor. If the AKI improves to grade 1 or less, taper steroids over at least four weeks, otherwise we might see recurrence. If there is no recurrence, a physician might discuss resumption of immune checkpoint inhibitor with patient after taking into account what are the risks and what are the benefits. Resumption of immune checkpoint inhibitor can be considered once steroids have been successfully tapered to 10 milligrams per day or less, or discontinued. However, if elevation persists for more than seven days or worsens, and no cause is found, then the grade 2 AKI needs to be treated as grade 3. Now grade 3 and grade 4 AKI are managed similarly. Grade 3 AKI is defined as creatinine more than three times the baseline, or more than 4 milligrams per deciliter, or when hospitalization is indicated. And grade 4 AKI defined as an AKI associated with life-threatening consequences, when dialysis is indicated, or creatinine six times above baseline. Management includes nephrology consult, evaluation for alternative causes, and permanent discontinuation of immune checkpoint inhibitor. If they are directly implicated in renal toxicity, the administration of corticosteroids in grade 3 or grade 4 AKI is at an initial dose of 1 to 2 milligrams per kg per day of prednisone or its equivalent. If and when the AKI improves to grade 1, corticosteroids can be tapered over at least four weeks. However, if elevation persists for more than three to five days for grade 3 or more than two to three days for grade 4 or worsens, we should consider additional immunosuppression, such as infliximab as a time frame, cyclophosphamide, cyclosporine, or mycophenolate. Usually, reflex renal biopsy is typically not necessary or recommended unless the AKI is refractory to steroids or other immunosuppressive agents. BRITTANY HARVEY: I appreciate your reviewing those details for immune related renal toxicity. So then, in your view, Dr. Swami, how will these recommendations for the management of renal toxicities impact both clinicians and patients? UMANG SWAMI: This guideline presents a concise, up to date, and a stepwise approach to diagnose, grade, and treat this rare, but serious side effect of immunotherapy. In my view, this would be immensely helpful to clinicians in busy practices. Prompt identification and treatment is also expected to help our patients experiencing immune related kidney injury. For patients, it will provide a readily available document to refer to for information regarding side effects of immune checkpoint inhibitor therapy. I applaud the efforts by the ASCO and the authorship team in developing the patient focused version of this guideline. This may allow patients, especially when between clinic visits, to identify this unusual condition and seek medical help in a timely fashion. BRITTANY HARVEY: Great. Thank you for highlighting the importance of this guideline, for all your work you did on this guideline, and for your time today, Dr. Swami. UMANG SWAMI: Thanks so much, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can find many of our guidelines and interactive resources in the free ASCO guidelines app, available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Musculoskeletal Toxicities: Management of irAEs Guideline (Part 7)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 8, 2021 10:20


An interview with Dr. Maria Suarez-Almazor from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews identification, evaluation & management of musculoskeletal toxicities in patients receiving ICPis, including inflammatory arthritis, myositis & polymyalgia-like syndrome in Part 7 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Maria Suarez-Almazor from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on musculoskeletal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Suarez-Almazor. MARIA SUAREZ-ALMAZOR: Thank you. BRITTANY HARVEY: First I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for the guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Suarez-Almazor, do you have any relevant disclosures that are directly related to these guidelines? MARIA SUAREZ-ALMAZOR: Thank you, Brittany. I don't have any disclosures directly related to the guidelines. BRITTANY HARVEY: Thanks very much. Then getting into the content of this, what are the immune-related musculoskeletal toxicities addressed in this guideline? MARIA SUAREZ-ALMAZOR: There are three major musculoskeletal syndromes covered in this guideline-- inflammatory arthritis, myositis, and polymyalgia rheumatica. BRITTANY HARVEY: Great. Then let's start with that first one that you mentioned. So what are the key recommendations for identification, evaluation, and management of inflammatory arthritis? MARIA SUAREZ-ALMAZOR: The diagnosis of inflammatory arthritis is primarily based on a thorough joint exam to detect the presence of synovitis and how many joints and what joints are actually involved. For this reason, we recommend early referral to a rheumatologist. From a diagnostic perspective, we recommend testing for antinuclear antibodies or ANA, rheumatoid factor, and cyclic citrullinated peptide antibodies or anti-CCP. These are only positive in 10% to 20% of patients but may be indicative of a more persistent disease. As inflammatory arthritis does not have any specific biochemical parameters for follow up, we use inflammatory markers such as sed rate and CRP in conjunction with the clinical exam as indicators of disease activity. For grades 1 and 2, we recommend treatment with nonsteroidal anti-inflammatory drugs or NSAIDs, or low-dose steroids up to 20 milligrams of oral prednisone or equivalent. If there is involvement of only one or two joints, local treatment with steroid injections can be indicated. For grade 3 and higher, the dose of steroids can be increased up to 0.5 to 1 milligram per kilogram of body weight. And if there is no improvement within two weeks or if the steroids cannot be satisfactorily tapered, we recommend early initiation of a disease-modifying antirheumatic drug or a DMARD, such as methotrexate, hydroxychloroquine, or sulfasalazine. We need to understand though that these may take up to two or three months to be effective. Alternatively, we can use biologic agents which have a faster onset of action. Recommended agents include tumor necrosis factor or interleukin 6 receptor inhibitors. In severe cases, immune checkpoint inhibitors may need to be permanently discontinued. But the overall goal is to try to continue therapy while we treat the adverse event. BRITTANY HARVEY: Understood. Appreciate your reviewing that information for inflammatory arthritis. Following that, what are the key recommendations for identification, evaluation, and management of myositis? MARIA SUAREZ-ALMAZOR: Well, myositis is really the most serious of the musculoskeletal toxicities. And it can be life threatening, especially when it's associated with myocarditis and with myasthenia gravis features. It usually presents with proximal weakness of the upper and lower extremities and sometimes with myalgia and even rhabdomyolysis. It usually is very acute in its presentation. Specific testing includes muscle enzymes, creatine kinase and aldolase, and electromyography and muscle biopsy if the diagnosis is uncertain. MRI can be useful as it can show muscle inflammation. And it can also assist in identifying a location for a biopsy if needed. Consultation with rheumatology and neurology should be requested early on. We also recommend that all patients undergo testing of cardiac enzymes such as troponin. And if elevated, a cardiology consultation should be placed right away and further testing performed. For grades 1 and 2, if patient has symptoms, treatment with corticosteroids are 0.5 to 1 milligram per kilogram should be initiated. For patients with grade 3 or 4, checkpoint inhibitors should be discontinued and the patient should be hospitalized. Corticosteroids should be initiated at a dose of 1 milligram per kilogram of prednisone or equivalent. And patients with severe compromise may need intravenous corticosteroid doses at higher doses of 1 or 2 milligrams per kilogram or even higher. For severe disease or if there is myocarditis or concomitant myasthenia gravis, we can consider plasmapheresis. IVIG can also be used, but it has a slower onset of action. And it is important to remember that plasmapheresis can remove immunoglobulins. So if it is to be used, the IVIG should be administered after the plasmapheresis is completed. There are other immunosuppressant therapies such as biologic agents that can also be considered. And sometimes for maintenance, oral immunosuppressants such as azathioprine, methotrexate, or mycophenolate mofetil can also be considered. Patients with severe disease may need to permanently discontinue the checkpoint therapy. BRITTANY HARVEY: OK, those details are helpful for clinicians. So then, for the last category, addressed in this guideline that you mentioned, what are the key recommendations for identification, evaluation, and management of polymyalgia-like syndrome. MARIA SUAREZ-ALMAZOR: Polymyalgia rheumatica syndromes present with marked pain and stiffness of the muscles in the shoulder and hip girdles. But some patients can also present with concomitant inflammatory arthritis. The workup is very similar to that of arthritis. In these patients, it is very important though to obtain a creatine kinase so that the muscle enzyme to be certain that the myalgia is not from myositis, as a treatment would be very different. Although very rare, polymyalgia, in some instances can be associated with giant cell arteritis which, if present, would require more aggressive treatment. For this reason, it is important to ask the patient about symptoms such as headache, visual disturbances, or jaw claudication. The management of polymyalgia-like immune adverse events alone, without any associated vasculitis, is very similar to that of arthritis. So we would use NSAIDs and low-dose steroids for grade 1 and 2. Higher doses of steroids and disease modifying agents, including biologics, might be needed for grades 3 and 4. But overall, very similar management as that of inflammatory arthritis. BRITTANY HARVEY: Great. Thanks for reviewing all of those recommendations for those three different categories. So then, in your view, Dr. Suarez-Almazor, how will these recommendations for the management of musculoskeletal toxicities impact both clinicians and patients? MARIA SUAREZ-ALMAZOR: Thank you, Brittany. For the most common rheumatologic adverse events, such as arthralgia, inflammatory arthritis, or polymyalgia-like syndromes, because they are not life threatening, we may not be as worried. But we need to recognize that they can greatly impair quality of life. So we really hope that these recommendations can assist patients and clinicians in the early recognition of symptoms and also in initiating prompt treatment so our goal to be able to continue checkpoint inhibitor therapy can be achieved by controlling the symptoms that really impair quality of life. Myositis is a much more serious adverse event that can lead to death. Patients may not be able to restart immune checkpoint inhibitor therapy again after they develop myositis. So we hope that these recommendations do highlight the need for very prompt diagnosis, consultation with specialists, and very aggressive treatment early on to control and manage these devastating, life-threatening adverse event. BRITTANY HARVEY: Definitely. Early recognition, treatment, and improved quality of life are key. So I want to thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Suarez-Almazor. MARIA SUAREZ-ALMAZOR: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.ASCO.org/supportive-care-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

Cancer Stories: The Art of Oncology

A physician attempts to ease a patient's pain, a painful moment somewhat eased by the joy of music.   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   RICHARD LEITER: Ode to Joy. "Is now an OK time?" I asked as I quietly entered the dimly lit room on a Saturday afternoon. "Yes, we've been waiting for you," my patient's wife Julie responded in the same calm, composed voice she had maintained all week. "Before we start, what questions do you have?" "I think you answered all of them this morning. I'm ready. Tom is ready. We just don't want him to suffer anymore." "OK, we'll get started." When I was in training, I had seen my preceptors initiate palliative sedation, but this was my first experience doing so as an attending physician. After being dormant for so long, my impostor syndrome returned. Though I was confident that I was taking the clinically-appropriate next step, I was nervous. I asked Tanya, our charge nurse and the nurse who was primarily caring for him over the last few days, to draw up the syringe. She did so with practiced confidence and handed it to me. I held it between my fingers, wondering how slowly I would need to push it to ensure the 2 milliliters of midazolam went in over a full five minutes. Tanya cleaned off the side port of his IV. I twisted the syringe into place. I looked up at Julie. She squeezed Tom's hand. I had first heard about Tom nearly a week earlier, when my colleague was handing off the service to me. "He's in his 50s, metastatic cancer. He was home on hospice and came in yesterday with uncontrolled pain. We started him on ketamine and he looks much better. The plan is to wean his ketamine, increase his methadone, and get him back home, hopefully in the next day or two." Stoic from years of pain from cancer eating away at his bones, Tom lay in bed with his eyes closed, his furrowed brow the only sign of his ongoing agony. When the nurses tried to move him, he screamed. After we weaned his ketamine, his pain quickly worsened. We increased methadone and hydromorphone. Neither gave him adequate relief. We restarted ketamine, but it proved to be no match for his pain. On rounds one morning, Julie asked if Tom could make it home. I told her I didn't think so and explained how worried I was about his pain. If we sent him home, I was concerned the pain would force him to come right back. Julie told me her kids would be disappointed, but that they'd understand, as she did. Easing Tom's suffering was more important. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. The hospital bed his family had set up in the living room would remain empty, a physical manifestation of cancer's unending cruelty. We talked about what would come next. If further titrating his medications proved ineffective, which I worried it would be, we would need to consider palliative sedation. "Whatever you need to do," Julie responded, her voice barely betraying the exhaustion I imagine she was feeling. Palliative sedation is a procedure used to relieve refractory suffering in a terminally-ill patient. Clinicians carefully sedate the patient, often to the point of unconsciousness, to relieve symptoms such as pain, nausea, shortness of breath, or agitated delirium. It is a procedure of last resort, and in our hospital, requires the approval of two attending physicians and the unit's nursing director. Though palliative sedation may shorten a patient's life, ethicists and clinicians have long regarded it as acceptable because its goal is not to hasten death but rather to relieve suffering. This is known as the doctrine of double effect, by which an action with at least one possible good effect and at least one possible bad effect can be morally permissible. Back in his room on that Saturday afternoon, I looked over at Tanya, the nurse, then at Harry, my fellow, who had been caring for Tom all week. I took in a breath under my mask, then slowly began to inject the contents of the syringe into his IV. In the quiet, I could hear the music coming from Julie's phone, which she had placed on the pillow beside his head. A pianist played a slow, mournful rendition of the final movement of Beethoven's Ninth Symphony, the Ode to Joy. In my head, I sang along. (SINGING) Joyful, joyful, we adore thee. I went to a traditionally Anglican school. 600 boys of all faiths and backgrounds, we'd rise each morning in assembly and sing hymns together. We cheered, yelled, and thumped on our pews-- a few minutes of raucous togetherness before we devolved into the usual bullies and cliques for the rest of the day. Tom's room couldn't have been more different. He remained completely still. Though Julie held his hand, he was alone, as we all felt in that room. (SINGING) Hearts unfold like flowers before thee, opening to the sun above. I felt the soft resistance of the syringe's plunger hitting the barrel. I looked back up at Tom. His chest fell, but didn't rise. I waited. He didn't breathe. The music slowed down. I felt Harry's eyes pivoting back and forth between my face and Tom's chest. I fixed my eyes on Julie's hands wrapped around her husband's. Despite the tension of the last week, she was calm, gentle. I matched my breath to hers. If she could exude such peace, so could I, I thought. I noticed Tom's hands. He had a piano player's fingers, long and slender. I pictured him sitting at the piano in their living room. I wondered who would take his place on the bench. I wondered if he could hear the song playing beside him. Had he and Julie chosen it for this moment? Did it bring back joyful memories, as it did for me? (SINGING) Melt the clouds of sin and sadness, drive the dark of doubt away. He didn't breathe. Did my first attempt at palliative sedation become euthanasia? Even if so, was this OK? I rehashed our conversations from the last few days. We talked about the risks. I went over the dose. Double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe. I thought about how I would explain Tom's death to Julie. I wondered if she would be angry, upset, relieved? With the help of my outpatient colleagues, they had spent years preparing for his death. His financial affairs were in order, and he had done legacy work with his kids. More than nearly anyone I had cared for, they were ready. Were we? Was I? (SINGING) Mortals join the happy chorus which the morning stars began. He breathed in. Not a grand gasp, a slow, soft inhalation. Tom's hand flexed ever so slightly around Julie's. In my head, I thumped a pew. [MUSIC PLAYING]   SPEAKER 2: Welcome to "JCO's Cancer Stories-- The Art of Oncology," brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. SPEAKER 3: The guest on this podcast episode has no disclosures to declare. [MUSIC PLAYING] LIDIA SCHAPIRA: Welcome to "Cancer Stories-- The Art of Oncology" podcast series. I'm your host Lidia Schapira. And with me today is Dr. Richard Leiter, physician and member of the Psychosocial Oncology and Palliative Care team at Dana-Farber Cancer Institute in Boston and the Brigham and Women's Hospital. Welcome to our podcast. RICHARD LEITER: Thank you so much for having me. LIDIA SCHAPIRA: It's a real pleasure. You submitted a beautiful narrative piece called "Ode to Joy." And I'd like to start today, Richard, by just focusing first on the case that you present to us. Let me tell you how I understand Tom's history, and then you can correct me if this is not the way that you'd like him to be understood. And remember, Tom is a man in his 50s who's lived with metastatic cancer to bones for years. In your narrative, you're very careful and document the fact that you've worked with many members of your palliative medicine team for a long time, that there had been many efforts to control his pain, his suffering, and he had to be hospitalized for pain management. He was already receiving home hospice care. There was a bed in the living room in the center of the family home. And he had a very supportive family and a wife that we'll call Julie at bedside. Is that the proper framing for the story? RICHARD LEITER: Exactly. Yep. Yeah. I think what I would add is that the goal was really to control his pain and get him back home. LIDIA SCHAPIRA: So now you're there as the fresh attending in palliative medicine, and you're called in, and it becomes quite clear to you after a few days of changing his medications that the pain is refractory. And that it-- you note here that he screams when he is moved, that the level of pain reaches what you have called agony. So tell us a little bit more about how a palliative medicine consultant or physician approaches this kind of situation in hospital today. RICHARD LEITER: Yeah, no. Great. Thanks so much. So we were, I would say, lucky enough to have him on our intensive palliative care unit, where we're caring for patients with difficult and sometimes refractory symptoms at any stage of the disease. So not only for end of life. But we do see a number of cases like his every year, every few months, where someone is getting closer to the end of life. The goal is to really focus on intensive symptom management. And their symptoms are challenging to control. So I think the first step, always, is a good history, right? Where is this pain coming from? What treatments have they tried already? What's worked? What hasn't? We're going to titrate medications, but select medications based on that and titrate them. I think someone who has been involved with my outpatient colleagues and has been receiving hospice services at home has often gone through many treatment modalities. So it's really taking what they've been on before and starting to add to it. So for Tom, I had inherited him from one of my colleagues, who had admitted him a couple of days earlier. And at that point, he was already on a hydromorphone infusion and ketamine, as I talk about in the piece. Ketamine had been started, hopefully, as a bridge to get him back home. And he had been on methadone, which is one of our most potent agents for, not only nociceptive pain, so our basic kind of bony pain or visceral organ pain, but also if there's pain with a neuropathic component. Methadone is an opioid that can be particularly effective there. So I think it's saying, OK, well, have we hit all of our receptors in managing their pain? Are we managing the anxiety on top of that? Are we doing everything we can? Are there procedures that we could do to help with their pain? Sometimes we're talking about intrathecal pumps for instance. And obviously, that's a more involved discussion. How much time does someone have left? Are the goals really to put them through a procedure in order to get their pain under control? But we frequently work with our interventional pain colleagues to tease out whether a procedure would be helpful for a particular patient. So those are the thoughts that always go through my mind when I'm approaching someone with severe cancer-related pain. LIDIA SCHAPIRA: So this is a very thoughtful approach. And I think one of the messages is that it seems palliative medicine and pain management are integrated into the care of patients with advanced cancer, which is a very important message for our listeners and our readers. And here you are, you have all of this, you have good communication, it seems, with your team members, with the patient's family, and there's nothing more that you can think of doing. And you're now starting to think about interventions that we normally don't think of, except as a last resort. Bring this to the bedside. Tell us a little bit about the recommendation for palliative sedation and when that's indicated in care. RICHARD LEITER: Yeah. So palliative sedation, as I write in the piece, it's a measure of last resort. And certainly, in our hospital's protocol, it explicitly states it's when all other options have been tried. As we start to integrate more options, it's always a conversation we're having among our team-- is when is palliative sedation truly indicated. How many boxes do we need to check before going down the palliative sedation route? And I think-- so we started to think about-- we had him on ketamine. We tried to wean him off, it didn't go well. We restarted ketamine. We started dexmedetomidine, which can be useful. Precedex, the brand name, they oftentimes use it in the ICU for sedation, but we find that it can be helpful in cases of refractory pain as well. And my practice has been-- and though I haven't gotten to palliative sedation until this case-- when I'm thinking about Precedex, I'm also starting conversations with the patient or their family, and certainly our team, about palliative sedation to say if this doesn't work, this is where we're headed. LIDIA SCHAPIRA: And why is this situation so difficult, so personally anxiety-provoking for you? You do use words that convey that you are feeling nervous, or perhaps even anxious. Tell us why. RICHARD LEITER: I think it's-- relieving our patient's suffering, relieving their families suffering is certainly the core of much of medicine and very much the core of what we do in palliative care. And I think to have someone in just such a terrible situation-- putting aside the pain, right? This is a man who's dying of his cancer, has a relatively young family. That alone is an awful situation. And my job is to make that situation a little bit less bad, is to ease the suffering. LIDIA SCHAPIRA: And there's something about this particular procedure, however, that adds a level of intensity and nervousness for you, and that is that perhaps-- you can describe this better than I-- but the fact that in some cases, this could have the unintended effect of actually causing respiratory depression or even hastening death and something that you have explained in your piece, if I understood you correctly, as the double effect. Did I get that right? RICHARD LEITER: Yeah, that's right. So the worry or one of the considerations with palliative sedation is that it could hasten someone's death. Oftentimes, the doses of the medications that we're using, if we're titrating them slowly, there are studies that show that it doesn't necessarily. I do think, though, when we tie it into withholding artificial nutrition and hydration, in that case, had the person been awake enough to eat and drink before, we do know that it would probably hasten their death, right, from that part of it, but not necessarily the sedation aspect. So double effect is basically saying this is ethically OK-- and there are a number of criteria. But if we are intending the good effect and not the bad effect and that it's proportional to the gravity of the situation so that not every patient who comes in with bad pain undergoes palliative sedation. LIDIA SCHAPIRA: My favorite line, Richard, in the piece-- and one that I now have read probably dozens of times-- is this-- "the double effect, I reassured myself. Even so, as bedside nurses have told me, it's easier to talk about philosophy when you're not holding the syringe." And that just gives me goosebumps thinking about it. What did you feel when you were holding the syringe? RICHARD LEITER: Exactly as I wrote about. There's all of the cognitive processes going on. And I ran it by another attending, I ran it by the nursing director, I ran-- everyone was on the same page, that this was medically indicated in this situation. And yet, when I'm standing there in the room-- patient, his wife, my fellow, and the nurse-- and I'm the one holding the syringe, watching the medication go in, it felt completely different to me. And there's a power that comes with it. In one sense, I felt like I was there for my patient. Here I am, standing here doing this to ease his suffering. And then the other, the unintended consequences of the sedation are real, and that feels different when you're the one physically doing it. LIDIA SCHAPIRA: I think one of the incredible gifts you've given us as readers is to share this with us and really adds a different dimension to the discussion of the complexity of what it is to be present, not just as a witness, in this case, but as somebody, as you say, with a power to really control so many things in the situation. And I thank you for sharing that with us. And question to you is, did writing about it in any way help you process this emotional, very powerful experience? RICHARD LEITER: Absolutely. I write to process. I write when I feel like I have something to say. And oftentimes, I write when a particular moment struck me. And I think that that moment, sitting there, pushing the medication, waiting for that breath while the music was playing was so poignant for me that I walked out of the room and I remember thinking to myself that night as I was decompressing on my walk home from work, I think I need to write about this. LIDIA SCHAPIRA: So thank you for writing about it, and then, of course, for submitting for review and to share it with people. Let me bring the music in. Music is such an important part of our sensory experience. So as you were holding the syringe, Julie, Tom's wife, puts the phone on the pillow and she plays the piano version of Ode to Joy from Beethoven's Ninth Symphony, which I want to play for our listeners now. [MUSIC PLAYING]   So Ode to Joy meant something, clearly, to Tom and Julie. And you said that you watched-- perhaps you were watching for his reactions. But tell me a little bit about what it meant to you. You sprinkled your essay with the lines for the choral for Ode to Joy, which has a religious significance as well. So tell us a little bit about that. RICHARD LEITER: Yeah. So I grew up in Toronto. I went to an all-boys school there that had a traditionally Anglican background, though I'm not-- I'm Jewish. We would sing hymns. And over the course of my time there, the hymns became less denominational and more multicultural and inclusive. And it was a moment-- it was a nice moment where everyone got into it. It's 600 boys singing, and so I still remember the words to Ode to Joy vividly. Anytime I hear it, I can replay the words in my head. And I found myself, in those moments in the room, really thinking about it. And the words were still-- as I was processing and watching Tom and Julie and making sure I was pushing the medication at the right speed, there was this soundtrack. It's a strange moment too, because they're good memories for me, and yet I'm in this incredibly solemn, intimate moment in my patient's room. LIDIA SCHAPIRA: And so as we're getting to the end of the piece and there's all of this tension that you've built up in the writing and the narrative-- and here you are, you're waiting and you hear the music and so on-- and then you finally let the tension out and he breathes. It's not a huge breath, but it's a soft, slow inhalation. And you see that the hand is flexed slightly around his wife, so he's still breathing. And you finish with this line that you say, "In my head, I thumped a pew." And I have to ask you about that. What does that mean to you? RICHARD LEITER: Yeah. So in that moment, it was relief, is what it was. Just the sense of, OK, this went-- it's my first time doing this, and this went OK. He appears more comfortable. He is still breathing. This is OK. And it just brought me back when we would thump the pews as we were singing the hymns. Our principal did not like it, but-- [LAUGHTER] But I think it was just that it was relief. I hesitate to say it was joy because I don't think there's joy in a situation like that, in the room. But there was a sense of satisfaction maybe, or professional satisfaction, the, OK, this is what we can do. And as bad as the situation is, there was something that we could do to make him somewhat more comfortable. LIDIA SCHAPIRA: Well, I certainly learned a lot. I wonder if now that some time has passed since this event, if you have any additional reflections on how this story has impacted your professional delivery of care, or perhaps the way you teach others, and if there are any parting comments that you'd like to leave us with. So I haven't had another case where I've needed to do palliative sedation, though we've thought about it in a couple of cases. I do think it's helped me, when I talk about palliative sedation with our trainees, to add the emotional valence. I think I was pretty good at talking about the importance of making sure everyone's on the same page and talking to the patient and the family and nursing staff. But to really talk about the significance of that moment for us as clinicians and how it does feel different-- at least it did for me-- and I think drawing on my personal experience is helpful in teaching it to the fellows that it's OK to feel like that when you're doing this. LIDIA SCHAPIRA: There are moments in medicine-- certainly in what you do-- that are really difficult. And this, probably, I would imagine, ranks as one of the top things. And it should never be easy. It will never be easy. The day that you think it's easy, you need to find something else, right? RICHARD LEITER: I think that's right. I think that's right. LIDIA SCHAPIRA: Well, thank you so much, Richard. You made me laugh, you made me cry reading this, and I thank you very much. My last question is, have you had a chance to talk with Tom's widow Julie about what that moment felt like to her? RICHARD LEITER: I have not, although I hope to in the near future. LIDIA SCHAPIRA: And that will be your next piece for us. [CHUCKLES] All right. Well, thank you very much and until the next time. Hope you all enjoy reading Ode to Joy. RICHARD LEITER: Thank you so much. SPEAKER 1: Until next time, thank you for listening to this "JCO's Cancer Stories-- The Art of Oncology" podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. "JCO's Cancer Stories-- The Art of Oncology" podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Endocrine Toxicities: Management of irAEs Guideline (Part 6)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 5, 2021 14:06


An interview with Dr. Jennifer Mammen from Johns Hopkins University, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of endocrine toxicities in patients receiving ICPis, including thyroid-related irAEs, primary AI, hypophysitis, and diabetes in Part 6 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Jennifer Mammen from Johns Hopkins University in Baltimore, Maryland, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on endocrine toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Mammen. JENNIFER MAMMEN: My pleasure, Brittany. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Mammen, do you have any relevant disclosures that are related to these guidelines? JENNIFER MAMMEN: I do not. BRITTANY HARVEY: OK. Thank you. Then, to start us off, what are the immune-related endocrine toxicities addressed in this guideline? JENNIFER MAMMEN: Yeah. So irAEs affect the thyroid and the pituitary most commonly. But we also addressed the possibility of primary adrenal toxicity and also the emerging toxicity of insulin-dependent type 1 diabetes, which, while rare, can present with grade 4 toxicity in the form of diabetic ketoacidosis. BRITTANY HARVEY: Understood. Then, starting with adverse events affecting the thyroid, what are the key recommendations for identification, evaluation, and management of thyrotoxicosis? JENNIFER MAMMEN: So thyrotoxicosis after ICI exposure is almost entirely due to subacute thyroiditis. That's a transient inflammation of the thyroid gland that causes a few weeks of high levels of thyroid hormone, followed by at least several weeks of hypothyroidism as the stores of thyroid hormone are replenished. In the irAE context, many patients do not ever actually recover adequate thyroid function and will remain hypothyroid, requiring thyroid hormone long term. Because the thyrotoxicosis is transient and results from the release of preformed thyroid hormone, anti-thyroid drugs do not help and actually can even make the hypothyroidism phase worse. Therefore, the treatment is really supportive care with beta blockers in particular to control symptoms of the hypothyroidism, such as tachycardia, tremor, or anxiety. BRITTANY HARVEY: In addition to those points for thyrotoxicosis, what are the key recommendations for primary hypothyroidism? JENNIFER MAMMEN: Yeah. So primary hypothyroidism is very common both in the general population and now in this population as a result of thyroiditis. Many patients might actually already be on thyroid hormone when starting immunotherapy. When the pituitary is working, the pituitary hormone thyrotropin or TSH is a reliable indicator of the adequacy of thyroid hormone replacement. And the goal is to use a dose of thyroid hormone that maintains the TSH in the mid reference range, generally between 1 and 3 million international units per liter. When a patient is first presenting or diagnosed with hypothyroidism, for example, in that second phase of thyroiditis, a weight-based dose can be used to estimate the needed replacement dose. For those with higher BMI, generally, an ideal body weight rather than an actual body weight gives a better estimate. And those specific recommendations are in the guidelines. Proton pump inhibitors, calcium/iron supplementation, or GI inflammation can all decrease the absorption of thyroid hormone. And so even the thyroid hormone is really common, and many oncologists are used to managing it, it can be tricky in these patients if there's issues with malabsorption. And so, therefore, an endocrinology consultation can be helpful to titrate and ensure that the dosing is adequate. Once that adequate dose, that stable dose is found, if other factors don't change, dose requirements are generally quite stable and can be monitored annually either by a primary care physician or an oncologist. BRITTANY HARVEY: Great. Those are important points. Then, addressing the immune-related adverse event that impacts the pituitary, what are the key recommendations for identification, evaluation, and management of hypophysitis? JENNIFER MAMMEN: So hypophysitis is inflammation of the pituitary, as you said. And although there are five hormone systems at risk, it's actually most common that the thyroid and the adrenal gland axes are what are affected. The diagnosis is made by a combination of assessing the pituitary hormone and the primary hormone, in this case, the thyroid hormone and cortisol along with the TSH and ACTH, which is the pituitary hormone that regulates the adrenal gland. With primary gland failure, as we said, the pituitary hormones will be elevated. But in hypophysitis, the problem actually comes from the pituitary. And so TSH and ACTH will be low or inappropriately normal for the low primary thyroid hormone level. There are several key points for oncologists who might need to initiate therapy before the patient can see endocrinology. First, thyroid hormone increases the metabolism of cortisol. And so if you've diagnosed central hypothyroidism due to hypophysitis, it's really important to replace cortisol, if needed, before replacing thyroid hormone, because in someone with both deficits, thyroid hormone alone can precipitate an adrenal crisis. Thus, the ASCO Guidelines really emphasize the need to assess both before starting thyroid hormone and also give the option to use steroids empirically, if needed, since the diagnosis can be sorted out later by an endocrinologist. A second important point is that headaches, visual changes, and diabetes insipidus, which is loss of fluid and generally marked by hypernatremia, those are much more common with metastatic disease in the pituitary rather than hypophysitis. And so such symptoms should really prompt a pituitary MRI when they're found in the setting of hormonal losses. The management of central hypothyroidism is similar to that of primary hypothyroidism. But as I said, the TSH is no longer a reliable marker for adequate replacement. So the goal, then, shifts from a TSH in the reference range to a free T4 at the upper half of the reference range. Adrenal insufficiency, as with thyroid hormone insufficiency, is managed by physiologic hormone replacement, and that's best done using hydrocortisone. This is a short-acting steroid that can be given in a way to imitate the natural diurnal rhythm. We use 2/3 of the dose in the morning and 1/3 in the early afternoon, allowing levels to fall as they naturally would overnight. Dose-titration is based on symptoms. And usually, 15 to 25 milligrams of a total daily dose is adequate to control symptoms from adrenal insufficiency. I do think all patients should see endocrinology at some point if they have been diagnosed with hypophysitis because they do need education on sick day rules, otherwise known as stress dosing, and also to be instructed on wearing an emergency alert bracelet or necklace or something. Long-acting steroids can be used for patients who have adherence problems. And of course, those long-acting steroids are more appropriate for the treatment of any other irAE that a patient may develop. While on higher doses of prednisone, patients can discontinue hydrocortisone and then restart it when the prednisone dose is weaned down below 5 milligrams daily. If there's a question about whether the central adrenal insufficiency is from hypophysitis or due to suppression after weaning off high-dose exposure, use of hydrocortisone because of the diurnal rhythm actually allows the adrenal axis to recover normally. And so after weeks, you can test for adrenal recovery using a morning endogenous level 24 hours after the last dose is given, which is another advantage to using the hydrocortisone mode of hormone replacement. BRITTANY HARVEY: Understood. And I appreciate you highlighting those key points for oncologists. Then, following that, what are the key recommendations for primary adrenal insufficiency? JENNIFER MAMMEN: Yeah. So primary adrenal insufficiency, you'll see the ACTH elevated just like in primary thyroid disease, and the cortisol will be low. Again, this situation is actually much more common with metastatic disease, and therefore, imaging is called for if you find that pattern of hormonal changes. It's been case-reported to happen with irAEs, but in general, this is incredibly rare. The management of hydrocortisone replacement for people with primary adrenal insufficiency is really the same as for hypophysitis. We're using hydrocortisone with that diurnal physiologic replacement pattern. Primary adrenal insufficiency, however, also generally results in the loss of mineralocorticoid function. And so most patients also need at least a low dose of fludrocortisone replacement. BRITTANY HARVEY: OK. And then the last adverse event addressed in the endocrine toxicity section of this guideline, what are the key recommendations for identification, evaluation, and management of diabetes? JENNIFER MAMMEN: Yeah. So diabetes in this patient population is very tricky because so many of these patients are getting high-dose steroids as part of their chemotherapy regimens, and this can cause a lot of hyperglycemia. And I think it's actually easy to become complacent about seeing blood glucoses in the 200s. And in fact, most of the hyperglycemia will be just that, secondary to steroid exposure and worsening type 2 diabetes. It can be managed with a titration of routine medications. But they are now increasingly less rare but still rare events of acute loss of pancreatic function, presumably autoimmune, that can be accompanied by life-threatening diabetic ketoacidosis. And the challenge for oncologists, I think, is to have a low enough threshold to investigate a suspicious pattern of hyperglycemia, for example, hyperglycemia with complaints of polyurea or, on physical exam, a more rapid respiratory rate that could indicate compensation for metabolic acidosis. So it's really a question of being a good clinician and taking the diabetes in context and not just assuming that it's due to steroid exposure. This is, I think, important because, like I said, diabetic ketoacidosis can be a grade 4 emergency, and patients can end up in the intensive care unit, needing a lot of intervention, which if we have a higher suspicion in clinic, we might be able to avert by getting rapid communication with endocrinology, starting people on insulin and that kind of an approach. BRITTANY HARVEY: Definitely. A common theme with these toxicities seems to be early identification is key. So thank you for reviewing the high-level recommendations for each of these toxicities. In your view, how will these recommendations for the management of endocrine toxicities impact both clinicians and patients? JENNIFER MAMMEN: Yeah. So I think making diagnoses in the hormonal systems can be complex and does require attention to the interactions, like we were talking about, between the pituitary and the primary gland. It's not something that oncologists necessarily have front of mind. And yet hormone replacement is actually quite straightforward. Once the need for it is recognized, since there's no side effects from replacing a hormone at an appropriate dose, it's just a replacement. And so, therefore, rapid diagnosis and initiation of hormone replacement can really allow patients to continue immunotherapy with a very minimal disruption, even in the face of an endocrine irAE. Although at our institution the close coordination between treating oncologists and endocrinologists is available, that's certainly not true everywhere. And I think that the ASCO Guidelines are designed to try and help oncologists make these diagnoses and initiate therapy to stabilize patients and even allow them to continue treatment while awaiting any necessary consultations, even in the case of thyroiditis, perhaps, managing what's a self-limited event and then moving on, which reduces the burden on patients with other priorities to focus on. BRITTANY HARVEY: Great. Those are very important points. So I really want to thank you for all of your work on these guidelines. And I appreciate you taking the time to speak with me today, Dr. Mammen. JENNIFER MAMMEN: It's my pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
Lung Toxicities: Management of irAEs Guideline (Part 5)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 4, 2021 10:47


An interview with Dr. Jarushka Naidoo from Johns Hopkins University, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of lung toxicities in patients receiving ICPis, focusing on pneumonitis in Part 5 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network-- a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcast. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Jarushka Naidoo from Johns Hopkins University in Baltimore, Maryland. Author on management of immune related adverse events in patients treated with immune checkpoint inhibitor therapy, ASCO Guideline update, and management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy ASCO guideline. And, today, we're focusing on lung toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Naidoo. JARUSHKA NAIDOO: Thank you. It's my pleasure to share updates on this guideline. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with a publication of the guidelines in the Journal of Clinical Oncology. Dr. Naidoo, do you have any relevant disclosures that are directly related to these guidelines? JARUSHKA NAIDOO: Yes. So I have research funding in the last two years from Merck, AstraZeneca, and Bristol Myers Squibb. And I also have served in a consulting role-- or an advisory board capacity-- for Merck, AstraZeneca, Bristol Myers. And not specifically related to this work, but also Pfizer, Takeda, Daiichi Sankyo, and Kaleido Biosciences. BRITTANY HARVEY: OK. Thank you for those disclosures. Then-- getting into the content of this guideline-- what are the immune-related lung toxicities addressed in this guideline? JARUSHKA NAIDOO: Thanks, Brittany. So the main lung toxicity that is addressed in this guideline is immune checkpoint inhibitor pneumonitis, which-- as this audience knows-- is an uncommon, but potentially fatal toxicity particularly associated with anti-PD-1 or PD-L1 monotherapy, but can also occur with combination immunotherapy approaches. In the guideline, we go through what is known about the natural history, risk factors, and then, of course, our comprehensive approach to identifying, evaluating, and managing this toxicity, which is defined as a focal or diffuse inflammation of the lung parenchyma. We also identify that, while pneumonitis is the quintessential lung toxicity that can occur with immune checkpoint inhibitors, we also note that there are some other lung toxicities that have been reported on, but for which we relatively little. And this includes sarcoid-like granulomatous reactions, including subpleural micronodular opacities and hilar lymphadenopathy, as well as pleural effusions. And these have been associated with both CTLA-4 and the PD-1, PD-L1 immune checkpoint inhibitor therapies. BRITTANY HARVEY: I appreciate that overview. So then, you mentioned the main toxicity here is pneumonitis. What are the key recommendations for identification, evaluation, and management of pneumonitis? JARUSHKA NAIDOO: Thanks, Brittany. So yeah, this is a key focus of the guideline. So, as we're aware, pneumonitis is defined as a focal or diffused inflammation of the lung parenchyma and is a toxicity that was identified as one of the early toxicities in the early clinical trials of the PD-1 inhibitors. The incidence of this toxicity is estimated at anywhere between 0% and 10%, and in large meta analysis, looks to be around 2% to 3% in terms of incidents. In terms of how to evaluate patients with suspected immune-related pneumonitis, the common symptoms would be cough, shortness of breath, fever, and chest pain. And in a patient who has suspected pneumonitis, some of the first tests to be done would be to take a pulse oximetry and to do some chest imaging. Chest imaging is preferable with a CT scan with contrast in order to rule out alternative etiology, such as pulmonary embolus For patients who are symptomatic-- which means CTCAE grade 2 or greater-- we also recommend a standard infectious workup, which is guided by institutional guidelines. But based on our ASCO guideline, we outline that this should include, at a minimum, a nasal swab, sputum culture and sensitivity, blood culture and sensitivity, and urine culture and sensitivity, as well as a standard COVID-19 evaluation. When we come to the diagnosis of pneumonitis, we then evaluate that in terms of CTCAE grade. Where the grade of pneumonitis refers, firstly, to whether a patient has symptoms, and the proportion of the lung parenchyma that may be involved with pneumonitis on chest imaging. Broadly speaking, patients with grade 1 pneumonitis are asymptomatic and usually identified on radiographic imaging almost incidentally. For these patients, we would recommend either holding immunotherapy or proceeding with close monitoring. And we recommend that patients should have weekly physical exams and pulse oximetry offered, and consideration of further chest imaging if the diagnosis is uncertain, or to follow progress-- usually around every three to four weeks-- or, if a patient becomes symptomatic, it may be more often than this. We also recommend that we may consider doing spirometry or DLCO evaluation as a repeat in these patients. Broadly, again, in terms of the evaluation of patients-- if patients are symptomatic from pneumonitis, which means they have a symptom related to radiographic features, then this would be called grade 2. And usually, radiographically, patients have more of the lung parenchyma involved-- greater than 25%-- and require a medical intervention. And the management would be prednisone, 1 to 2 milligrams per kilogram per day, that is then tapered over 4 to six weeks, and immunotherapy is held during that time. Importantly, in order to knuckle down the diagnosis of pneumonitis, we recommend consideration of doing a bronchoscopy with bronchoalveolar lavage sampling in order to truly rule out alternative infectious diagnoses or lymphangitis carcinomatosis. And for this reason, a transbronchial biopsy can also be considered. In some cases, we also consider treating with empiric antibiotics to cover infection if we feel that this remains in the differential diagnosis. If patients do not clinically improve after 48 to 72 hours on prednisone, then we recommend treating at a higher grade, meaning grade 3, where patients have severe symptoms, hospitalization is required, and a larger proportion of the lung parenchyma is involved. For these patients who have grade 3 or greater pneumonitis, we recommend permanently discontinuing immunotherapy, administering a higher dose of steroids at methylprednisolone, 1 to 2 milligrams per kilogram per day. And, once again-- if there is no improvement after 48 hours, we recommend a range of potential additional immunosuppressive approaches, which include either infliximab, mycophenolate mofetil, intravenous immunoglobulin, or cyclophosphamide. And there are currently no recommendations as to which may be the optimum immunosuppressive approach, but there are a number of clinical trials aiming to elucidate the answer to this. Importantly, overall in patients who are symptomatic, it may also be appropriate to consult pulmonary medicine and infectious diseases teams to weigh in on the diagnosis and management going forward. BRITTANY HARVEY: Great. Thank you for that clear, step-wise approach to the evaluation and management of pneumonitis. So then, in your view, Dr. Naidoo-- how will these recommendations for the management of lung toxicities impact both clinicians and patients? JARUSHKA NAIDOO: I think it's very important for both clinicians and patients to be aware of the potential side effects of the treatment that patients are receiving with immune checkpoint inhibitors. We know that some toxicities from immunotherapy tend to be mild and can be managed quite well with corticosteroids or other approaches. What we understand about lung toxicities is that, thankfully-- in the majority of cases-- pneumonitis will be well-controlled with corticosteroids and holding of immunotherapy. However, in a proportion of patients, pneumonitis may become severe and may even lead to treatment-related deaths. And for that reason, both patients and clinicians need to be aware of what to look out for in terms of the symptoms of pneumonitis, and how to diagnose and manage this toxicity quickly and efficiently in order to avoid poor outcomes. BRITTANY HARVEY: Absolutely. Those are excellent points for both clinicians and patients to keep in mind. So I really want to thank you for all of your work on these guidelines and for taking the time to speak with me today, Dr. Naidoo. JARUSHKA NAIDOO: You're very welcome, Brittany. And thank you to the ASCO oncology community for the opportunity to share this important work. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO eLearning Weekly Podcasts
Oncology, Etc. – On Leadership and Pearls of Life with Dr. Susan Desmond-Hellmann (Part 1)

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Nov 4, 2021 25:49


Part one of this two-part Oncology, Etc. episode features an inside look at the amazing career of Dr. Susan Desmond-Hellmann (spanning from early AIDS research in Kenya and drug development at Genentech, to serving as UCSF Chancellor and CEO of the Bill and Melinda Gates Foundation). Hosted by Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas). Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/04/21

ASCO Daily News
Tackling the Increasing Incidence of Early-Onset Colorectal Cancer

ASCO Daily News

Play Episode Listen Later Nov 4, 2021 21:09


Dr. Mohamed Salem, gastrointestinal medical oncologist at the Levine Cancer Institute at Atrium Health in North Carolina, tells guest host Dr. John Sweetenham, associate director of clinical affairs at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, about the disturbing rise of early-onset colorectal cancer, the impact of socioeconomic disparities on patient outcomes and potential interventions to improve detection.   Transcript Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director of Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and guest host of the ASCO Daily News podcast today. I'm delighted to welcome Dr. Mohamed Salem, a gastrointestinal medical oncologist at the Levine Cancer Institute at Atrium Health in North Carolina. Dr. Salem is going to be discussing with us the disturbing rise in early onset colorectal cancer and the impact of socioeconomic disparities on patient outcomes and potential interventions to increase screening, particularly in younger populations. Mohamed, many thanks for joining us on the podcast today. Dr. Mohamed Salem: Thank you, Dr. Sweetenham for the kind invitation. And I have to tell you, I'm very grateful for this invitation to cover this topic. And also, thanks to the ASCO Daily News team for shedding the light on this. Dr. John Sweetenham: Great. Before we start, I should mention that my guest and I have no conflicts of interest relating to the topic today. Full disclosures of all guests on the ASCO Daily News podcast are available on our transcripts at ASCO.org/podcast. Mohamed, low socioeconomic status has been associated with worse survival in patients with colorectal cancer, otherwise known as CRC. But there hasn't been as much focus on the impact of socioeconomic status for those patients who have early onset colorectal cancer and, specifically, I guess, we mean by that, those patients who develop this condition in early adulthood. Of course, it's quite well known, generally, that adolescents and young adult patients who develop various types of cancer appear to have worse outcomes than both their childhood and their adult counterparts. Your study, published in The Oncologist, looked at the impact of sociodemographic disparities and insurance status on survival of patients with early onset colorectal cancer and, maybe not surprisingly, in some respects, based on experience in other diseases, demonstrated worse outcomes. Could you talk to us a little about the data in your study and how that might inform programs to improve early detection and treatment of patients with colorectal cancer? Dr. Mohamed Salem: Sure. As you mentioned, Dr. Sweetenham, there are two problems. A socioeconomic problem, which is, by itself, a huge challenge we are facing as a community. On the other hand, two, this colorectal cancer problem in younger adults is another issue that we have been facing now for maybe a decade or two. Rebecca Siegel just published a paper a couple of years ago showed that the increased incidence of [colorectal] cancer in adults, it's on the rise. And it brings many challenges to this population in terms of the diagnosis, their care, and their outcome. But when you couple this with the challenge that socioeconomic status impact on the outcome of our patient, this becomes a very, very complicated problem. So, our group wanted to look not only on the impact of socioeconomic status, but the impact on that problem on patients with early onset colorectal cancer and see how complicated this will be to their outcome. We examined more than 30,000 patients, and we chose the cutoff [at age] 40. Early onset definition could vary a little bit, so you have 40, you have 45, some people think even 50, but we choose 40 just because we wanted to focus on the very young group. We utilized National Cancer Database and we obviously thank them for giving us access to this data. And we tried to look at the impact of socioeconomic status, and it was stunning. We found that survival decreased with the decrease of socioeconomic status. So, the patient who carried the best survival was those with highest socioeconomic status and then the lower SES goes, the worse is their survival outcomes. And also, not just survival. We found that if you have low socioeconomic status, you are more likely to have stage III or IV tumors, which is, as you know, more advanced cancer, you're more likely to have node-positive disease, and also, you're more likely to present with stage IV colon cancer. So, just to highlight how impactful the socioeconomic status or factor in the presentation in disease and the outcome, and not only this one. We will also looked at insurance status. It was very clear that patients with no insurance or Medicaid, they do much worse. They had the higher risk of mortality compared to patients with commercial private insurance. And you have to wonder having this issue with being young adult and having a cancer and then having no insurance, have no means to access care. That's something, as you mentioned, perhaps we could, as a community, look into it and try to remove those barriers, to hopefully improve the patient outcome. Dr. John Sweetenham: Yeah, one of the things that struck me from looking at your paper was the fact that stage to stage, age for age. If patients had insurance, it did mediate some of the adverse prognostic effects of socioeconomic status, if I read the paper correctly, which does suggest to me that part of the problem at least is access to care. Would you agree with that? Dr. Mohamed Salem: I totally agree, 100%. And it's also interesting that we even looked at multiple angles. We looked at uninsured, by itself. We looked at Medicaid insurance. We looked at private versus not private. And it doesn't matter how we look at it, and adjusting for all other co-founders and stage, insurance status played a significant role on the impact of survival for those patients. Dr. John Sweetenham: Very interesting that I think that there are several other studies in other diseases which are beginning to show very similar emerging patterns. Just moving on from that a little, I think remarkable numbers that stood out from the studies which you cite in your article in The Oncologist is that 2015 study by Bailey et al. which was predicting that, by 2030, the incidence rates will have increased really quite substantially. And for the younger age group, those aged 20 to 34, the estimate was at a 90% increase in incidence. And for those in the 35 to 49 year age group, the suggestion was that incidence rates would increase by almost 28%, so I think there are a couple of questions that I have regarding that. The numbers are pretty sobering. Can you talk to us a little bit about what we know about the factors that are driving this increase in incidence? Dr. Mohamed Salem: Sure. I do agree with you, Dr. Sweetenham. I think this are very alarming numbers and very alarming phenomena. I'm sure you remember when we're in medical school and fellowship, we used to think colorectal cancer is a disease of older people. Unfortunately, now, we're seeing younger patients getting this. Not the age of 50 or 40 or 30 as you mentioned, even 20 years old. My youngest patient is 17-years-old. And it's not uncommon for me to see patients who are like 20-21 years old coming with this disease. There are many risk factors for colorectal cancer, as you know, obesity, diabetes, tobacco, alcohol, exercise, and other genetics and hereditary reasons. But the truth is that many of those patients come to our clinic are fit. They eat well, they don't smoke, they don't drink, so it appears there is something else going on. And there are many theories going into this, but the truth is that we're actually not sure 100% what are the exact reason for that rise in incidence among young adults. Some people think microbiome might have a role here. Some people think obesity, as I mentioned, has more impact on younger people than older people, but I think also is this is an area of research now. And we hope they'll continue to look into this and try to identify the exact reason why this is happening. But I also wanted to touch base a little bit about an important issue, because the paper you cited, both the American Cancer Society and the task force took the screening or issued recommendations regarding the screening to be from [age] 50 to go now to 45. We used to have a screening recommendation at age of 50 for average risk. Now, as of 2018, the American Cancer Society said you should be screened at 45, and most recently, the task force said the same thing. However, if you think about it, our study looked at patients who are [age] 40. So, the change in the screening really is not going to impact them, because it's still not even at the age of screening and, therefore, education, outreach and educating our patients, our population about the risk and the symptoms and signs of this disease is extremely important  because it makes a huge difference if the cancer gets detected at stage I, which most of the prime surgery is enough and 99% of patients or more than 90% of patients would be cured and don't even need anything besides surgery, versus, as I mentioned, when they start to come into the office with stage IV disease. Now, it's a totally different story and totally different outcome. Dr. John Sweetenham: Yeah, and I guess one of the other questions, the whole screening strategy issue is obviously a very big issue right now and I guess somewhat controversial as well. But I think it's true to say, and if I'm wrong, I stand corrected, that in general, compliance with screening as a whole tends to diminish with age. So, I'm sure, for all kinds of reasons, many of which may be kind of socioeconomic, financially-related, younger individuals are less likely to get screened, either because of insurance or what other issues they may have. And so, I wonder as age goes down, and I'd make the assumption that it may be true, that compliance with screening protocols also goes down. It'll be interesting to speculate on what are going to be useful interventions, particularly in that very young age group, might lead to earlier detection of colorectal cancer in, let's say, a 22-year-old. It can be a difficult issue to unravel, I think. Dr. Mohamed Salem: I totally agree. I think it gets very complicated very quickly because, one, as you mentioned, access to care and coverage and being able to afford this is one issue. But also, if you think about it from logistics, younger people need to work. Maybe they have kids, they need to take care of them. They already have a busy schedule and busy life going on to begin with. So, for them, to take the time off and start to do this office visit takes away time from them, so it affects the compliance. So, hopefully, more awareness and more recognition and encouraging each other to take a day off and just go to get screened might actually result in life saving. Also, I would like to say something important. Most of us, as physicians, when we see an older patient with rectal bleeding, for example, we always think about, OK, maybe he has colon cancer, maybe she has colon cancer. But we don't think the same way when we see a 25 year-old old bleed. So, I think, as a family doctor or somebody who is a medical doctor that will actually seeing that patient, the threshold should be lowered for symptoms and also for early referral. And the other thing I would like to encourage your viewer is that none of us would be excited and happy to talk to their loved one or their friend about his or her old habits as having their rear bleeding, abdominal colics, or so on, and so forth. But sometimes, those symptoms are the symptoms because of colon cancer. I always say, you know your bodies are best, so if you thinks there's something wrong, don't be embarrassed to talk about that. You have to share those symptoms with your family doctor, or at least your loved one to get an advice and get evaluated. And this gets complicated among minorities, because somehow there is a shame in this. And I think looking for safe environment, community network, as you mentioned at the beginning, easy access to medical care is crucial. You're not going to be able to get screened if you don't have the bus ticket to get to the center to be screened there. The last thing I would just like to stress also, if I may, most people think a screening is connected to colonoscopy, which is partially true, but colonoscopy is not the only way patients can get screened. There are many, many other ways that people can get screened including stool tests that you can do at home and send it to your doctor. So, colonoscopy is not the only way you can get screened. You can also discuss with your family doctor or even loved one about other means that you can get screened. Dr. John Sweetenham: Yeah, I think that's a really important point, and it raises another question actually, which may be difficult to answer in this specific age group. But I just wonder, in general terms, whether you can make any comments about how much ground do you think we may have lost during the pandemic in terms of delayed screening and delayed diagnosis. Are you are you seeing evidence of that in the literature or in your own practice and your own institution now? Dr. Mohamed Salem: I think that's a pretty important question. I would say yes to both. Last year, there was data showing that colorectal cancer cases declined. All of us know nothing had change. I mean, the cases are the same out there. It's just not been diagnosed yet because most hospitals obviously, including ours, and many, many other hospitals throughout the country were trying to survive the COVID-19 pandemic, and that got a lot of patients to be delayed for screening. Many patients didn't feel comfortable going to the hospital to get either their colonoscopy or even to the family doctor visit, and so on, and so forth. So, I think this delay in the detection of the cancer. The cancer did not didn't appear. It just was not detected yet. And the risk of that, as I mentioned earlier, the more time passed without intervention, if someone has a cancer, that means more advanced stage. It goes from stage I to II and III and IV with time, and with that, the survival and outcomes get worse. So, that also brings another point that we think, it's that younger patient has more aggressive disease. I think there is some data about that. But also, I wonder if is this really more aggressive disease or just delayed in diagnosis. When you go to your family doctor or even get it checked then they say they're having rectal bleeding. This could be, yes, because of hemorrhoid, but also, it could be because of colon cancer. And I'm not saying everyone with rectal bleeding has colon cancer, but I'm saying that could be one of the reasons. And I would say you really have to seek medical advice if you have symptoms because, again, early detection is the best part about this, and it really saves lives and it changes a lot of things. So, yes, it's a pandemic. It had definitely, no doubt, impact on the colorectal cancer care. And I would predict is that we're going to start seeing more and more patients with more advanced disease in the coming months and years. Dr. John Sweetenham: Yeah, that's an alarming prediction. Of course, taken in conjunction with the other prediction that we mentioned earlier from the study by Bailey et al., it really should give us cause for concern. And I think, maybe my final question to you would be, given what you've just said, plus those data in somewhat dire predictions for 2030, what do we need to do now to prevent that prediction from Bailey et al. from coming true, do you think, if there's anything we can do at this stage? Dr. Mohamed Salem: I think that's a very complex question. But I think, the way I think about this, every one of us, as an individual and organization and even in government and political entity, we really have a role to play. As an individual, I would say, as I mentioned before, you know your body well, so I always say this phrase, 'If you feel something, say something.' This could be a life changing behavior. So, if you feel like there's something wrong with you, please don't be embarrassed to share this. Talk to your family doctor, talk to your friend, and seek medical advice. As a community, we have to encourage each other to share this information, to teach each other certain habits that might help early detection. And if you are at risk, please go ahead and get screened. As I mentioned, colonoscopy is one mean, but there are many others. As an institution, I think raising awareness is important. I think providing easy access to care, that's also very important. And from the government and political entity, I think looking at those people with diversity and disparity, and people with no insurance, people who need special support and need to get help, I think we should have a community program out there. Some help out there, whether this comes through insurance, means, or other programs that we need to look at. And I think this might have some impact on our ability to detect this cancer early on. I always say, which, I think maybe some people might think is an exaggerated statement, but no one really should die from colorectal cancer. Because again, if you detect the cancer early, minimal care should take care of that. The problem happens when we don't detect it early and the patient presents with stage III or IV disease. Dr. John Sweetenham: Yeah, so it's kind of a multifaceted approach, everything from the personal right through to the political aspect is involved in what we all need to do to contribute to this. So, I really appreciate your time today and sharing your insights, and congratulations on the study, which, I think, highlighted actually not just one, but several really important issues in this kind of growing incidence of colorectal cancer and what appeared to be growing disparities as well. Thanks so much for joining me on the podcast today. I hope that you continue to make an impact on these disturbing trends in the years to come. Dr. Mohamed Salem: Thank you, Dr. Sweetenham, for having me, and it's a pleasure to be with you tonight. Dr. John Sweetenham: And thank you also to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts.   Disclosures:  Dr. John Sweetenham: None disclosed.  Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

ASCO Guidelines Podcast Series
Gastrointestinal Toxicities: Management of irAEs Guideline (Part 4)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 3, 2021 8:37


An interview with Dr. Yinghong Wang from MD Anderson Cancer Center, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She discusses the identification, evaluation, and management of gastrointestinal toxicities in patients receiving ICPis, including colitis and hepatitis in Part 4 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Yinghong Wang from the University of Texas MD Anderson Cancer Center in Houston, Texas, author on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on gastrointestinal toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Wang. YINGHONG WANG: Thank you, Brittany. It's my great pleasure to be invited to participate in this education event. I'm happy to share my experience and the knowledge that I learned over all the research studies in this field and share with the readers or the community providers on this specific topic. BRITTANY HARVEY: Great. Thank you. Then, first, before we get into the content, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Wang, do you have any relevant disclosures that are directly related to these guidelines? YINGHONG WANG: I do have consulting services to two pharmaceuticals, but they're not related to the current guidelines that are published from the ASCO. They're Tillotts Pharma and Athenex Pharma. BRITTANY HARVEY: OK. Thank you. Then, let's talk about these gastrointestinal toxicities. So first, what are the immune-related gastrointestinal toxicities addressed in this guideline? YINGHONG WANG: So these particular guidelines have provided very detailed description on the incidence and clinical presentations and also recommendations on the evaluation and treatment for the upper and the lower gastrointestinal adverse events and the liver and even other organ toxicity, including the exocrine pancreas toxicities that are being categorized as GI field related to checkpoint inhibitor treatments. BRITTANY HARVEY: OK. And then what are the key recommendations for the identification, evaluation, and management of colitis? YINGHONG WANG: So colitis is definitely one of the most common organ to be involved in this category of toxicity-related checkpoint inhibitors. And that's why a lot more studies have been studied because the patient volume can allow enough power to run a lot of analysis. I think the summary that I would say-- the recommendations from the current ASCO Guidelines include the early recognition and evaluation with close monitoring for people who had suspicious symptoms for gastrointestinal adverse events and early stool inflammatory marker evaluation even in patients who had grade 1 symptoms. And very important to rule out alternative causes of the symptom presented, like infections or cancer metastases or some other medication-related side effects other than checkpoint inhibitors. And the other important component of evaluation is endoscopy and the pathological evaluation for patients who had a positive stool inflammatory markers or if the patient has a presentation of colitis symptoms like bleeding. And also, the presence of ulcers on the endoscopy usually has been found to predict a steroid refractory disease course. Therefore, the early initiation of more potent treatment like biologic agents, such as infliximab or vedolizumab, is very critical. The other alternative medical treatment, like ustekinumab or tofacitinib or even fecal transplantation for refractory cases, should also be considered in the small portion of patients. The disease monitoring while on the medical treatment is critical via the repeat endoscopy or following the fecal calprotectin level to guide the duration of treatment and the time to resume immune checkpoint inhibitor treatments if indicated. The rechallenge of these checkpoint inhibitors is possible among patients with GI toxicities, and the risk of GI toxicities is completely manageable. That's the brief summary of the GI recommendations. BRITTANY HARVEY: Yeah. Thank you for that summary. And then just in addition to those key recommendations, is there anything additional about the identification, evaluation, and management of hepatitis? YINGHONG WANG: Yeah. The hepatitis-- the incidence is not as common as colitis but can be severe in extreme cases. So it requires the equal attention to recognize and evaluate for liver toxicity after checkpoint inhibitors with close monitoring. We also need to rule out other alternative causes of the symptoms, including the infections, alcohols, iron overload, thromboembolic events, cancer metastases, et cetera. The imaging, on the other hand, is more critical for liver toxicity evaluation. This is a little bit different from using the endoscopy and biopsy for luminal GI tract toxicities. And the liver biopsy should also be considered in certain select cases through all other differential diagnosis and also the other alternative treatment other than corticosteroid, including azathioprine and mycophenolate mofetil, that are mentioned in the small case series and also listed in the current ASCO Guidelines. BRITTANY HARVEY: Great. Thank you for that overview for both colitis and hepatitis. So then, in your view, how will these recommendations for the management of gastrointestinal toxicities impact both clinicians and patients? YINGHONG WANG: Yeah. Given the increasing volume of patients experiencing the GI adverse events related to the checkpoint inhibitor cancer therapies and their related morbidities, so both the clinicians and patients need to be familiar with the clinical presentations and the time frame of onset to ensure early recognition and early diagnosis, especially serious complication and even mortality can occur due to the significant delay in appropriate treatment in extreme cases. So the updated guideline provided by ASCO and also other professional societies in the US or internationally can provide a great resources to the academic and community clinicians when they encounter these cases in their practice. So ultimately, the implementation of appropriate management and future prospective clinical trials in this field for these challenging conditions should improve the patient's outcome of toxicities and also cancer. And that's the goal of our clinicians and academia providers, to be able to serve the patient better in the future. BRITTANY HARVEY: Definitely. Well, thank you for sharing this summary with us today, for all of your work on these guidelines, and for taking the time to speak with me today, Dr. Wang. YINGHONG WANG: Thank you very much for this opportunity. Please let me know if you have any questions. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

Electro Vessel
Electro Vessel 168 | Soroush Yarahmadi

Electro Vessel

Play Episode Listen Later Nov 3, 2021 59:13


Electro Vessel is a weekly radio show distributed worldwide by Vessbroz. Each week the boys invite a guest to share the decks with them to showcase the very best in new and upcoming dance music from across the globe. The show has hosted artists like Nicky Romero, Timmy Trumpet, Julian Jordan, Vini Vici, Mike Williams, Swanky Tunes, Cat Dealers, DJ From Mars, and many more! The show also features the Track of The Future. The brothers each week select a promo or demo to play in the show they think will be big in the future. This week Vessbroz invited Soroush Yarahmadi. Follow Soroush Yarahmadi: https://www.instagram.com/soroush_yarahmadi/ 1. Vessbroz and Billy The Kit - Rise Again (Extended Mix) 2. DEADLINE & Outflux - No More Pain (feat. Loyal) [Club Mix] 3. ASCO, SoNick - Distraction (Original Mix) 4. Gabriel & Dresden feat. Jan Burton-Dangerous Power (Edu Imbernon Extended Remix) 5. Jennifer Cooke x Hreez - Show Me Love (Extended Mix) 6. Zheno, DJ Frog, Audiosonik - My Heart (Extended Mix) 7. Kasablanca-Hold Me Close (Vintage Culture Extended Remix) 8. Adele - Easy On Me (Henry Himself Remix) 9. Worshipper Burning Children (Stephen Hurtley Mashup) 10. Marteneez And M.J.E & Michael Chodo - Hell On Earth 11.Sunnery James & Ryan Marciano-Unseen Heroes 12-soroush yarahmadi-rave light 13-Dua Lipa - Levitating (Justus Rave Edit) 14-LUMX X Orange INC X Sb Mont - Champion (Summer 2021 LEC Playoffs Anthem) 15-Thomas Irwin - Fighting Till The End (Feat. Scarlett) 16-Adam Ferello - Oorja 17-SOROUSH YARAHMADI - PERSIAN PAISLEY 18-R3HAB & Gabry Ponte - The Portrait (Ooh La La) 19-Robert Falcon, THRILLION & JUSTN X - Ridin Solo' 20-Vessbroz - Worshipper 21-HEADER - Renaissance (Extended Mix) This show is syndicated & distributed exclusively by Syndicast. If you are a radio station interested in airing the show or would like to distribute your podcast / radio show please register here: https://syndicast.co.uk/distribution/registration

ASCO Guidelines Podcast Series
Cutaneous Toxicities: Management of irAEs Guideline (Part 3)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 2, 2021 11:52


An interview with Dr. Milan Anadkat from Washington University & Dr. Aung Naing from MD Anderson Cancer Center, authors on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” They discuss recommendations for cutaneous toxicities in patients receiving ICPis, including rash, bullous dermatoses & SCAR in Part 3 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey. And today, we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Milan Anadkat from Washington University in St. Louis, Missouri. And Dr. Aung Naing from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, authors on Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today, we're focusing on cutaneous toxicities in patients treated with immune checkpoint inhibitor therapy. Thank you for being here Dr. Anadkat and Dr. Naing. AUNG NAING: Thank you for having us. MILAN ANADKAT: Thank you. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Anadkat, do you have any relevant disclosures that are directly related to these guidelines? MILAN ANADKAT: As listed in the document, I don't have any direct disclosures. I do have a number of indirect disclosures, as I've consulted on similar topics in the past. BRITTANY HARVEY: Thank you. Then Dr. Naing, do you have any relevant disclosures that are related to these guidelines? AUNG NAING: I do not have. BRITTANY HARVEY: Great, then let's get into the content of this guideline and the cutaneous toxicities that we're here today to talk about. So Dr. Naing, what are the immune-related cutaneous toxicities addressed in this guideline? AUNG NAING: Well, with the advancement of immunotherapy, we've seen better response in our cancer patients. However, together with such positive outcomes, we are also seeing side effects caused by the immunotherapy. Disruption of the homeostatic mechanisms include a unique spectrum of side effects or immune related adverse events, commonly called IRAEs. The most common immune related adverse events in patients receiving checkpoint inhibitors are dermatitis, enterocolitis, transmitis, and endocrinopathies. However, if you look at the most commonly reported IRAE of any grade, it is dermatologic toxicity. So here in this guideline, we addressed how to take care of the patients when they are having these side effects, particularly with the cutaneous toxicities. So when you look at that time to median onset of skin toxicities, it ranges from two to five weeks. And using CTCAE criteria for grading is a challenge for skin toxicity, as it may not reflect the true picture. So, therefore, severity may be graded based on body surface area, tolerability, mobility, and durations. Those are the points also we discuss in this guideline. Broadly speaking, they are three groups of cutaneous IRAEs. They are rash inflammatory dermatitis, bullous dermatoses, and finally, Severe Cutaneous Adverse Reactions, SCAR. It is important to have thorough physical exam and rule out any other etiology of skin problems. In general, it's also important to work closely with our colleagues from dermatology. While some of those low grade skin toxicities could be treated in outpatient setting, consulting the cases with dermatologists is important for higher grades of skin toxicities, such as bullous dermatoses and SCAR. My colleague, Dr. Milan Anadkat, will follow with a discussion on the role of dermatologists in taking care of patients with cutaneous toxicities caused by immunotherapy. BRITTANY HARVEY: Thank you, Dr. Naing for reviewing those. So then you just mentioned three categories of toxicity. And I'd like to review the key recommendations for each. So Dr. Anadkat, starting with what is recommended for the identification, evaluation, and management of rash or inflammatory dermatitis? MILAN ANADKAT: Thank you, Brittany. And thank you Dr. Naing for teeing up this discussion. I think, as was mentioned, there are three major categories of cutaneous toxicity that are seen from immunotherapy. By and large, the most common is rash or inflammatory dermatitis, from which there are multiple different phenotypes or looks by which physicians may be seeing. The most common phenotypes within rash or inflammatory dermatitis, which account for over 90% of the cutaneous toxicity seen from immunotherapy, include lichenoid, which is a purple, flat topped bumpy rash that can involve the skin or the mucosal membranes. The psoriasiform, which resembles psoriasis, morbilliform, or oftentimes, maculopapular, which resembles a measles-like pink exanthem over the trunk, or generalized eczema and itching. So what's important is identifying the particular phenotype and categorizing it as an inflammatory dermatosis and excluding the other two phenotypes of cutaneous toxicity, such as bullous dermatoses or Severe Cutaneous Adverse Reactions. BRITTANY HARVEY: Great, and then moving into that second category that you both mentioned, what are the key recommendations for bullous dermatoses? MILAN ANADKAT: And so the key phenotypes for bullous dermatoses, by and large, is bullous pemphagoid, which is the most common phenotype seen in this category. Although other phenotypes resembling autoimmune bullous diseases, such as pemphigus or bullous drug reactions may also be seen. With bullous pemphigoid we see tense blisters, or tense bullae, frequently overlying a bed of erythema on the skin. Patients typically complain of considerable itching, far more than pain, with this category of eruption. BRITTANY HARVEY: Got it. Thank you for reviewing that for bullous dermatoses. So then the third group is Severe Cutaneous Adverse Reactions. So what are the key recommendations there? MILAN ANADKAT: And so the third group, being Severe Cutaneous Adverse Reactions, is a term used worldwide to encompass conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and DRESS or drug reaction with eosinophilia and systemic symptoms. These are, fortunately, rare, but can be life threatening skin eruptions. They account for less than 1% of all skin reactions seen from immunotherapy. When practitioners are approaching a patient who may potentially have one of these conditions, patients typically will exhibit symptoms of malaise, fatigue, fever, and a dramatic cutaneous eruption, which will either present with peeling or sloughing of the top layers of the skin, or a generalized erythema covered with multiple sterile pinpoint pustules. Oftentimes, there are associated symptoms of lymphadenopathy and organ toxicity that is noticed simultaneously, such as hepatotoxicity, or eosinophilia, or acute renal failure. BRITTANY HARVEY: Great, I appreciate you reviewing the identification of all three of those groups. So then I'd like to hear from you both on this last question. But in your view, how will these recommendations for the management of cutaneous toxicities impact both clinicians and patients? AUNG NAING: I would say that recognition of the toxicity is really important, particularly if you can actually catch the toxicity when it is in the mild grade. If you take care of them, then you can actually stop them from being mild to severe toxicity. That's number one. Number 2 is in that way, we may not have to halt or stop the immunotherapy treatment that could be beneficial to the patients. And also, working together with the dermatologists is very important, because as I discussed earlier, some of them, we could take care of as an outpatient. But there will be certain dermatology toxicities, where we need to work closely with our dermatologists. And please also remember that these are the guidelines. You will be seeing the patient in the setting. So I think using that guideline and clinical judgment, that would actually help our patients at large. MILAN ANADKAT: I think that's excellent. One, I think, important aspect of these guidelines is not only to correctly identify the phenotypes of cutaneous toxicity, but as Dr. Naing mentioned, it assists in management of these toxicities. The goal of these guidelines, especially as it pertains to the skin toxicity, is to accurately identify what toxicity is occurring for the patient, but then more importantly, to guide on appropriate management strategies to allow the patient to continue on immunotherapy and minimize or avoid unnecessary treatment interruption or treatment discontinuation. The guidelines assist in management strategies according to the severity by which patients present. And as mentioned, I think ultimate priority will be given to the practitioner directly treating the patient. But consideration towards not only extent of body surface area involved, but severity of cutaneous eruption is thoroughly reviewed. And in addition to phenotype, including such patient reported outcomes, such as degree of pain, itch, or interruption on activities of daily living help guide the degree of management that can be provided. BRITTANY HARVEY: Those are excellent points. I want to thank you so much for your work on these guidelines and for taking the time to speak with me today, Dr. Naing and Dr. Anadkat. AUNG NAING: Thank you. MILAN ANADKAT: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events. To read the full guideline, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

Cancer.Net Podcasts
Understanding Side Effects of Immune Checkpoint Inhibitors, with Tian Zhang, MD, MHS, and Afreen Idris Shariff, MD

Cancer.Net Podcasts

Play Episode Listen Later Nov 1, 2021 11:25


ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. In this podcast, Dr. Tian Zhang and Dr. Afreen Shariff discuss common and sometimes serious side effects caused by a type of immunotherapy called “immune checkpoint inhibitors.” They also explain why it is important for people with cancer to track the side effects they experience and discuss them with their health care team. Dr. Zhang is an associate professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also a Cancer.Net Specialty Editor. Dr. Shariff is an endocrinologist and assistant professor of medicine at Duke University School of Medicine and the Associate Director for the Multi-Disciplinary Toxicity Program at the Center for Cancer Immunotherapy at Duke Cancer Institute. Together Dr. Zhang and Dr. Shariff host a podcast called Checkpoint NOW discussing a multidisciplinary approach to managing side effects of immunotherapy. Learn more and listen at www.checkpointnow.org. View full disclosures for Dr. Zhang and Dr. Shariff at Cancer.Net. Dr. Zhang: Hi, everyone. Thank you for joining. My name is Tian Zhang, and I specialize in treating patients with kidney, bladder, and prostate cancers. I'm happy today to be joined by my wonderful colleague at Duke, Dr. Afreen Shariff. Dr. Shariff: Hello, everyone. I'm Dr. Afreen Shariff, endocrinologist, assistant professor of medicine, and associate director at the Center of Cancer Immunotherapy at Duke Cancer Institute. We're happy to talk today on the podcast Cancer.Net about immune checkpoint inhibitors and associated side effects that many patients often are concerned about. Neither of us have any disclosures related to this podcast content. Dr. Zhang: Thanks, Afreen. With the increase in use of immune checkpoint inhibitors for patients with cancer and the prevalence of side effects and toxicities, we thought it was important for patients to understand what side effects to monitor for and when to contact their doctors for further guidance and management. We thought we would put together this particular podcast to focus on side effect monitoring from a patient perspective. Dr. Shariff: I agree. We have some side effects that can potentially be attributed to multiple toxicities, but there are others that can be pretty straightforward. These are times when referrals to subspecialists like myself are necessary. And at other times, the treating oncologist primarily manages toxicities. The more patients know, the better prepared they will be when starting on immune checkpoint inhibitors. Tian, let's get started. When you are introducing a new start for immune checkpoint inhibitors to a patient in your clinic, what is your overall advice? Dr. Zhang: Afreen, I think it's so important for patients to understand the general scope of side effects to monitor for. These include rashes and diarrhea, which are more common and relatively straightforward to attribute, but also other nonspecific symptoms like fatigue. I start with an overview about common side effects of rash and diarrhea, discuss a little bit more about rare side effects of inflammation in the lungs or liver, and then talk about potential endocrine side effects. And we do that all when the patient's starting immune checkpoint inhibitors in my clinic. Dr. Shariff: Oh, that's great, Tian. What should patients know about diarrhea? Dr. Zhang: Sure. So diarrhea is reflective of inflammation in the colon, what we call colitis. And this can occur in mild form or in a more severe form and is 1 of the most common side effects of immune checkpoint inhibitors. Changes in stool caliber, particularly loose or watery stools, and also frequency per day should be quantified and noted. Diarrhea does not often have blood, but bloody stools are also possible and should be reported. If bowel movements while on checkpoint inhibitors increase to 2 to 3 times more per day above baseline, patients should start reporting these to their treating oncologists for further management. Dr. Shariff: Well, I'm sure our audience and some of the patients on immune checkpoint inhibitors will find this very useful. Now, skin rashes are seen quite commonly as well. For patients being treated with immune checkpoint inhibitors, what would you like them to know about these rashes? Dr. Zhang: Sure. Of course, skin rashes vary from mild to severe and treatment varies with the diagnosis. If patients notice blisters and pain, this can certainly be an emergency and needs to be evaluated further by their oncologist who may then refer them to a skin doctor for more treatment. Large patches of red rashes can also be concerning. In general, we start with topical steroids for mild rashes and then add on oral steroids if topical ones are not controlling the rash. Afreen, we see fatigue so often in patients treated with immune checkpoint inhibitors. Can you share some insight into different side effects that can cause fatigue? Dr. Shariff: Tian, this is a very important question and common concern expressed by many patients. Now, often it is difficult to identify the cause if fatigue occurs in isolation without any other symptoms. Now, fatigue can result from immunotherapy and from cancer itself. But what I want to emphasize is the difference between ongoing fatigue and profound fatigue, which is a severe version affecting everyday activity levels. When patients experience profound fatigue, it's important to know what other symptoms are present that can help with identifying a cause. Dr. Zhang: Great. And what other symptoms should patients be aware of? Dr. Shariff: Sometimes this occurs with headaches and vision changes, indicating a side effect causing inflammatory changes of the pituitary gland in the brain. If this is a concern, your oncologist will advise further testing and a referral to a hormone doctor like myself called an endocrinologist. Now, if fatigue occurs with rapid weight loss, increased heart rate, and tremors, these can be signs of an overactive thyroid called hyperthyroidism. Now, in contrast, fatigue with weight gain can indicate an underactive thyroid. Both of these thyroid-related side effects will require lab evaluation to confirm a diagnosis. Dr. Zhang: Afreen, fatigue is so common and also a presenting symptom for diabetes, as well. Can you tell us more about this? Dr. Shariff: Yes. Fatigue and weight loss are common in new-onset or worsening diabetes. With immune checkpoint inhibitors, you can see a rare side effect of insulin deficiency, which is called type 1 diabetes. It's a rare side effect and needs treatment right away. What makes the symptoms a little different is that this fatigue is seen with increased thirst and appetite and a high blood sugar, which helps with the diagnosis. Now, Tian, we also see fatigue with shortness of breath. Now, what side effects can cause this? Dr. Zhang: When a patient comes in with shortness of breath, we're often thinking about heart and lung toxicities from immune checkpoint inhibitors. Measuring oxygen saturation helps. Sometimes patients who have inflammation in their lungs, what we call pneumonitis, will have decreased oxygenation levels. In the clinic, if patients report shortness of breath on exertion, we will also obtain EKGs, echocardiograms, and other labs to evaluate for heart dysfunction. And often, subspecialists will help us in managing lung and heart toxicities from immune checkpoint inhibitors. Dr. Shariff: Excellent. Now, what other complications can we see in a patient treated with immune checkpoint inhibitors? Dr. Zhang: Liver dysfunction is 1 that we haven't talked about yet, and liver dysfunction is often without symptoms. Oncologists will monitor liver function generally every few weeks when patients are treated with immune checkpoint inhibitors. An elevation from baseline will spark suspicion that the immunotherapy is responsible, or other drugs. And often we will involve a liver specialist. And if, due to the immune therapy, we'll often treat that with steroids. Dr. Shariff: That's very helpful. Now, what about other toxicities like kidney toxicity and toxicities to the nervous system? Dr. Zhang: Sure. Certainly, these are rare forms of toxicities, the ones that affect the kidneys or neurologic toxicities. But they can certainly happen. For kidney toxicities, we would monitor kidney function on labs and sometimes would need to involve a kidney specialist. These are often primarily treated with steroids. Neurologic toxicities are rare but can be disabling and dangerous if diagnosed late. So patients can experience symptoms ranging from mild, like numbness and tingling, to more severe symptoms of weakness and paralysis. These situations often involve the input of a neurologist. Dr. Shariff: Thanks, Tian, for your insight on these rare side effects. Interestingly, some side effects may be picked up on labs while patients may not have any symptoms. This is why oncologists are often checking blood work with every treatment. And it's important to bring up symptoms when you do experience them while on treatment. While these side effects are concerning, it's important to have a conversation with your treating oncologist to weigh your risk for each of these side effects. Most importantly, remember that a majority of these less severe side effects are manageable and do not need interruption of immune checkpoint inhibitors. This is a general guidance, and it's important to always refer to your treating clinician. Dr. Zhang: Thanks, Afreen. I hope this session helps bring awareness for symptom management and side effects management for patients on immune checkpoint inhibitors. For other information on specific toxicities, there are several resources. You can follow us on Twitter at CheckpointnowMD, check out our podcast, Checkpoint Now, on Apple Podcast or Spotify, or also go onto the Cancer.Net website with more information on disease-specific treatments and toxicities. ASCO: Thank you Dr. Zhang and Dr. Shariff. To learn more about immunotherapy and its potential side effects, please visit www.cancer.net/immunotherapy. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO Guidelines Podcast Series
ICPi Overview: Management of irAEs Guideline (Part 1)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 1, 2021 13:01


An interview with Dr. Bryan Schneider from the University of Michigan Health System and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center, co-chairs of the Management of Immune-Related Adverse Events Guideline Expert Panel. They discuss an overview of the “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update” in Part 1 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and I want to introduce you to our series on the Management of Immune-Related Adverse Events. ASCO has developed two guidelines for the management of immune-related adverse events, one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. Today, we'll be focusing on an overview of the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. And we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy and an episode to discuss the management of immune-related adverse effects in patients treated with CAR T-cell therapy. Today, I am joined by Dr. Bryan Schneider from the University of Michigan Health System in Ann Arbor, Michigan, and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center in San Diego, California, co-chairs on Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update and authors of the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy, ASCO Guideline. Thank you for being here, Dr. Schneider and Dr. Bollin. BRYAN SCHNEIDER: Thank you, Brittany. KATHRYN BOLLIN: Thank you for having us. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Schneider, do you have any relevant disclosures that are related to this guideline? BRYAN SCHNEIDER: I have research funding to my institution from Bristol Myers Squibb and Genentech Roche at the time of panel formation. BRITTANY HARVEY: Thank you. And, Dr. Bollin, do you have any relevant disclosures that are directly related to this guideline? KATHRYN BOLLIN: No disclosures. BRITTANY HARVEY: Thank you. Then, let's talk about this guideline. So first, Dr. Schneider, what prompted this update to the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy Guideline last published in 2018? BRYAN SCHNEIDER: Yeah. The previous guideline was widely used and consistently one of the top read articles of the JCO over the last couple of years. And since the original guideline publication in 2018, new data have emerged on the management of immune checkpoint inhibitor toxicities. So our goal was to build on the original guideline with more treatment options, especially for patients who fail initial steroid treatment. New strategies have developed for the management of many toxicities, especially GI, cardiac, and heme toxicities. And ASCO and the panel felt it was important to present these new options to the providers in the community. We also wanted to add sections that the providers would find valuable, including a table with many of the immunosuppressive agents used with typical dosages and schedules. We also added a table of commonly conducted testing while patients are on high-dose steroids as this is something many medical oncologists may not be used to handling as we typically do not have patients on steroids at high doses for several weeks or even months. BRITTANY HARVEY: Understood. Then, in addition to those updates that Dr. Schneider just mentioned, Dr. Bollin, what is the general scope and purpose of this guideline? KATHRYN BOLLIN: Yes. So the immune-related adverse event management guideline update and the CAR T-cell toxicity guideline serve to provide physicians that are prescribing these therapies with an understanding of the wide range of known potential toxicities of these agents and the best available evidence-based and expert opinion recommendations for their management. So up to 70% of patients treated with immune checkpoints will experience some form of immune-related adverse event, and nearly all patients getting CAR T-cell therapies experience toxicity. So recognition of the occurrence of these toxicities and appropriate management are essential for optimizing patient outcomes. BRITTANY HARVEY: Definitely, those are key points. So then, Dr. Schneider, what are the overarching recommendations for the management of immune-related adverse events irrespective of the affected organ? BRYAN SCHNEIDER: I think early recognition of the side effect is critical. So the guideline has typical signs and symptoms of each toxicity to help clinicians decide if this is occurring in their patients. Second, I think it's critical to grade the toxicity. We often don't do that with side effects related to traditional chemotherapy outside of clinical trials. So for example, if a patient has a platelet count of 75, I can't think off the top of my head what grade that is. I just know I'm going to hold chemotherapy for a week or two. But grading of the toxicity of these immune checkpoint therapies really is very important to decide whether patients can just be watched, whether they need to start steroids or whether they need to be admitted. I think still corticosteroids and dose holds are the first steps that clinicians will do. The majority of these toxicities-- although it would be nice if we could personalize the treatment based on the particular side effect and what we see under the microscope if the particular affected organ is biopsied, I think, in broad strokes, corticosteroids can be implemented easily, and a lot of our oncologists can be comfortable doing this potentially without subspecialty help. Having said that, I think multidisciplinary care is a must for the higher-grade side effects as, in oncology, we can't pretend to also be cardiologists, gastroenterologists, neurologists, dermatologist, and so on. And although there may be varying degrees of comfort from our subspecialists regarding the management of these toxicities, we do need their help for shared decision making, especially for the steroid refractory toxicities. We always want to emphasize a slow steroid taper oftentimes over at least four to six weeks. We get into trouble when we try to get them off the steroid quickly because they do have side effects that the patient may not enjoy. But oftentimes, we try to taper them quickly, and the side effect comes roaring back. And then, finally, to escalate immunosuppression quickly if no improvement with high-dose steroids is observed, oftentimes, that's done even within just a few days. But commonly, in practice, there's still hope that the steroid will kick in two or three weeks down the road, and that's not a good strategy. If the patient's having significant symptoms and steroids aren't helping, they do need to go on to a more important immunosuppressant. BRITTANY HARVEY: Those are important notes on the overarching management, particularly on how the adverse effects are different than those in patients treated with chemotherapy and the importance of multidisciplinary care. So then, Dr. Bollin, in your view, how will this guideline impact clinical practice? KATHRYN BOLLIN: So the impact of this guideline update is actually very broad. As with the previous guideline, as Dr. Schneider alluded to earlier, it's been very frequently accessed by readers since it offers symptom outlines and algorithmic recommendations for early identification and the management of immune-related adverse events based on the severity and organ system involved. What's really important to understand is that while initially, as hematology-oncology physicians prescribing these agents, we're doing so in the setting of early phase clinical trials. We were learning about the toxicities, and those physicians were often managing the toxicities themselves. But now, with the exponential increase and the therapeutic indications for immune checkpoint therapies in cancer, the experience with the toxicities and their management and the questions have also followed suit with an exponential rise. With this guideline update, we have experts among all of the internal medicine subspecialties that are now guiding the hematology-oncology physicians in immune-related adverse event management. We enlisted the experts in crafting this guideline update. So in summary, this serves not only as a tool for the prescribing hematology-oncology physicians but also for all of the subspecialists in the community and within academic centers for optimizing patient outcomes in the setting of immune-related adverse events. BRITTANY HARVEY: Great. Yeah, it sounds like this update will be hugely important for practicing clinicians. So then, in addition to those points raised by Dr. Bollin, Dr. Schneider, what are the implications for patients receiving immune checkpoint inhibitor therapy? BRYAN SCHNEIDER: So we really hope this will be an essential tool to help providers quickly treat patients when these toxicities present. Often, this is unexpected, and busy clinicians may be blindsided by these issues. So these guidelines will provide a quick resource to guide the workup and formulate a treatment plan that will expedite patient recovery. And ultimately, this should help promote quality of life for patients on these therapies and may help reduce trips to the emergency department, hospitalizations, and potentially allow the safe rechallenge of immune checkpoint therapy after resolution of the side effect. Many centers have the advantage of subspecialty support with experience in managing these toxicities. But for providers who may not have immediate access to, say, hepatology or endocrinology, we hope these guidelines will help the oncology providers provide the best treatment to facilitate the optimal clinical outcome. BRITTANY HARVEY: Absolutely, those are key for optimal care. Then, finally, Dr. Bollin, looking toward the future, what are the important outstanding questions and developing areas of research for the management of immune-related adverse events? KATHRYN BOLLIN: So while our recognition of immune-related adverse events, the testing for them, and management strategies have greatly improved with the expanded use of and experience with these therapies, large gaps in our knowledge remain. Translational and basic science research efforts are underway to understand these gaps, such as with the intrinsic and extrinsic drivers of autoimmunity, such as those with HLA allelic variations and the microbiomes interplay with our immune systems. There are also research efforts underway to develop rapid diagnostic tests to deploy early in the onset of irAE signs and symptoms and for the development of biomarkers and modeling tools that will aid us in predicting which patients are likely to experience immune-related adverse events. There have also been some interventional protocols that have attempted to prevent these immune-related adverse events by incorporating immune suppressants along with therapeutic agents. But so far, promising results with this strategy remain elusive. In regard to treatment for immune-related adverse events, investigators are working to learn the best strategies for selective immune suppression rather than just the use of glucocorticoids that will control immune-related adverse events while maintaining the clinical benefit of these incredible anticancer therapies. BRITTANY HARVEY: Thank you for highlighting those research gaps and both of you for your efforts to lead this guideline update. We'll be joined by authors on the guideline over the next episodes to review the key recommendations for organ-specific management in patients treated with immune checkpoint inhibitors and to review the recommendations for patients receiving CAR T-cell therapy. Stay tuned for these episodes highlighting the sections of the guidelines. And thank you for your time today, Dr. Schneider and Dr. Bollin. KATHRYN BOLLIN: Thank you so much. BRYAN SCHNEIDER: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ASCO Guidelines Podcast Series
CAR-T Cell Therapy: Management of irAEs Guideline (Part 2)

ASCO Guidelines Podcast Series

Play Episode Listen Later Nov 1, 2021 30:13


An interview with Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center and Dr. Monalisa Ghosh from the University of Michigan Health System, authors on “Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline.” They discuss recommendations for management of irAEs in patients treated with CAR T-Cell Therapy in Part 2 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network. A collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. ASCO has developed two guidelines for the management of immune-related adverse events-- one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. In our last episode, you heard an overview of the Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Today, we'll be focusing on the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline, and we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy. Today, I am joined by Dr. Monalisa Ghosh, from the University of Michigan Health System in Ann Arbor, Michigan and Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center in New York, New York, authors on both Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline and Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Thank you both for being here, Dr. Ghosh and Dr. Santomasso. In addition, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Ghosh, do you have any relevant disclosures that are directly related to this guideline? MONALISA GHOSH: No. I do not have any relevant disclosures. BRITTANY HARVEY: Thank you. And, Dr. Santomasso, do you have any relevant disclosures that are directly related to this guideline? BIANCA SANTOMASSO: Yes. I'd like to disclose that I've served as a paid consultant for Celgene, Janssen Pharmaceutical, and Legend Biotech for advising them on the topics of CAR T-cell therapy side effects. BRITTANY HARVEY: Thank you. Then, getting into these immune-related adverse events-- first, Dr. Ghosh, can you give us an overview of the scope and purpose of this guideline? MONALISA GHOSH: Sure. The purpose of this guideline is to offer expert guidance and recommendations on the management of immune-related adverse events in patients treated with chimeric antigen receptor or CAR T-cell therapy. This guideline offers guidance on the diagnosis, evaluation, and management of the most common toxicities of CAR T-cell therapy, which includes Cytokine Release Syndrome-- or CRS-- and immune effector associated neurologic syndrome-- or ICANS. As well as other potential, but less common toxicities, such as Hemophagocytic Lymphohistiocytosis-- or HLH-- B-cell aplasia, prolonged and recurrent cytopenias, Disseminated Intravascular Coagulation-- or DIC-- and infections. BRITTANY HARVEY: Great. Thank you. Then, Dr. Santomasso-- looking at this guideline, there's a few overarching recommendations. So, what are those general recommendations for the management of immune-related adverse events in patients receiving CAR T-cell therapy? BIANCA SANTOMASSO: Yes. The overarching recommendations are, really, first to recognize that these side effects exist. And that, as such, it's important to recognize that patients who develop these toxicities or side effects after CAR T-cell therapy need to be evaluated, or managed in, or transferred to a specialty center that has experience with the management of these toxicities. They're new toxicities. This is a new therapy. And patients are increasingly going to be managed in, or treated in, the outpatient setting, and, as such, they need to remain within a short distance of the treating center for about four to eight weeks post-therapy, and they should then return to their treating center upon experiencing any toxicities. Finally, as its flu season and infection season, it is recommended that inactivated influenza and COVID-19 vaccination be performed on patients and also family members as well. And any patient who does have an active infection, the CAR T-cell infusion should be delayed until that infection has been successfully treated or controlled. I often make a final point, which is that the immunogenicity of and efficacy of COVID-19 vaccines is uncertain in these patients with these agents, but the potential benefits outweigh the risks and uncertainties for most patients. BRITTANY HARVEY: Thank you. Those are important points for patients and treating clinicians. So then, Dr. Ghosh-- as you mentioned, this guideline addresses the seven most common CAR-T-related toxicities, and I'd like to review the key recommendations for each of those. So let's start with, what are the key recommendations for identification, evaluation, and management of cytokine-release syndrome? MONALISA GHOSH: Well, Cytokine Release Syndrome is one of the two major toxicities that occur immediately or within a short time period after infusion of CAR T-cells. We have defined Cytokine Release Syndrome, or CRS, as an immune-mediated phenomenon that's characterized by various symptoms that are indicative of immune activation and inflammation. And patients may experience signs and symptoms that could include fever, hypotension, hypoxia, tachycardia, shortness of breath, rash, nausea, headache, and various other symptoms that are a little less common. These symptoms are caused primarily by the release of cytokines. Cytokines are the messengers of the immune system, and most of them are released by bystander immune and non-immune cells. We know that the onset of Cytokine Release Syndrome is variable depending on the CAR T-cell product that's used, as well as the patient population that's treated. But it generally occurs anywhere from two to seven days after infusion of CAR T-cells, and in some rare cases can occur even a little bit later. A standard grading system has been developed and grade CRS, or Cytokine Release Syndrome, based on three parameters-- fever, hypotension, or low blood pressure; and hypoxia or low oxygen levels. CRS is primarily managed with IL-6 antagonists because IL-6 is an inflammatory cytokine that has been shown to mediate a lot of the systemic effects that we see from Cytokine Release Syndrome. And one of the treatments is the monoclonal antibody tocilizumab, which acts against-- or blocks-- the IL-6 receptor. CRS that is refractory to tocilizumab is generally treated with steroids. Then there's limited experience with additional therapies, especially in the setting of CRS, that does not respond to tocilizumab or steroids. There are other anti IL-6 therapies available. For example, siltuximab, which binds to IL-6 itself rather than the IL-6 receptor. However, there have been no direct comparative studies of these agents. Anakinra, which is also an IL-1 receptor antagonist has also been shown to mitigate CRS in some CAR T-cell recipients that have high grade CRS. BRITTANY HARVEY: OK. Thank you for reviewing those management strategies. So, following that-- Dr. Santomasso, what are key recommendations for identification, evaluation, and management of immune effector cell-associated neurotoxicity syndrome? BIANCA SANTOMASSO: Sure. Immune Effector Cell-associated Neurotoxicity Syndrome-- also known as ICANS-- is the second most frequent severe toxicity that can be seen after CAR T-cell therapy. So, what is ICANS? These are transient neurological symptoms that occur in the days after infusion, most commonly with CD19 CAR T-cell therapy. And the clinical manifestations of ICANS include encephalopathy, which is confusion, behavioral changes, expressive aphasia, or other language disturbance, change in handwriting or other fine motor impairment or weakness, and tremor and headache can also be seen. In more severe cases, patients can become obtunded with a depressed level of consciousness or even develop seizures, and they may require a higher level of ICU care, such as intubation for airway protection. And in very rare cases, malignant cerebral edema may develop, which may be fatal. ICANS can occur at the same time as Cytokine Release Syndrome, or can also occur several days after or shortly after CRS resolves, so it's important to have a high index of suspicion even after Cytokine Release Syndrome has resolved, but typically the side effects are self-limited and occur within the one month after infusion. Most symptoms lasts between 5 and 17 days, and the time of onset duration and severity of ICANS may really vary depending on the CAR T-cell product used or the disease state of the patient. So, what do I mean by that? Patients with high disease burden seem to be at increased risk for severe ICANS, so kind of knowing the disease that the patient has and the burden of disease is important. And then also there may be product-specific differences as well, so reviewing the product label is important as well because each may have its own risk evaluation and mitigation strategies that inform both the duration and the frequency of monitoring for ICANS after infusion. For evaluation of ICANS, we recommend, again, the ASTCT ICANS grading system. These allow for monitoring of several different aspects of neurologic function in these patients. Mental status changes are really what define the onset of ICANS. So for CRS, it's fever; for ICANS, it's mental status changes. And the severity of the mental status change can be determined by a standardized score known as the ICE score, which stands for Immune Effector Cell-associated Encephalopathy score. This is a simple 10-point scoring metric where points are assigned for orientation to year, month, city, hospital, ability to name three objects, ability to follow simple commands, write a standard sentence, and count backwards from 100 by tens. And for children younger than age 12 or those with developmental delay, The Cornell Assessment of Pediatric Delirium, also known as the CAPD, can be used in placement of the ICE assessment. Prior to CAR infusion, patients should be evaluated, including with an ICE score, for their baseline neurologic status. And what's nice is that this ICE assessment can be used as a daily screen after CAR infusion for the onset of ICANS during at-risk period. Then, other than the ICE score, there are four other neurologic domains that contribute to ICANS grading, and that's level of consciousness, seizures, severe motor weakness, and signs and symptoms of elevated intracranial pressure or cerebral edema, and patients are graded according to the most severe symptom in any of the five domains. So for patients who develop ICANS, it's recommended that they have workup, including blood work, CRP, CBC, comprehensive metabolic panel, fibrinogen, and coagulation tests. Neuroimaging with a non-contrast CT of the brain should be done and considering MRI of the brain in patients who are stable enough. In addition, electroencephalogram and lumbar puncture should be considered. And the electroencephalogram is really to rule out subclinical seizures, and the lumbar puncture is to assess the opening pressure-- or the pressure within the central nervous system-- and also to send studies to rule out infection. And again, these all have to be considered on an individual case by case basis, but are things to keep in mind. So for treatment of ICANS, the mainstay of treatment is, really, supportive care and corticosteroids. Tocilizumab, while it seems to rapidly resolve Cytokine Release Syndrome and most symptoms, actually does not resolve ICANS and may worsen it, so steroids are really typically used. The typical steroid is dexamethasone at a dose of 10 milligrams, and the interval really depends on the grade of the ICANS. Because of the possibility that tocilizumab may worsen neurotoxicity, ICANS really takes precedence over low grade CRS when the two occur simultaneously. And patients who don't show improvement within 24 hours after starting steroids or other supportive measures should have CSF evaluation and neuroimaging. Often treatment of seizures-- many patients are put on Keppra and levetiracetam or other anti-seizure medicine if they develop ICANS, and patients with grade 3 or greater ICANS may need an ICU level of care and escalation of steroid doses. The steroids are continued until ICANS improves to grade 1 and then tapered as clinically appropriate. And the most important thing to remember is that ICANS just needs to be monitored very closely as patients may worsen as some steroids are tapered. They also may improve rapidly after steroids are started, so steroids should be tapered quickly as patients improve. And, again, as with CRS, there's limited experience with other agents, such as Anakinra and siltuximab, but those could be considered in severe or refractory cases. BRITTANY HARVEY: Understood. I appreciate you going through when and how clinicians should screen for ICANS and those key management points. So, in addition to that-- Dr. Ghosh, what are the key recommendations regarding cytopenias? MONALISA GHOSH: So cytopenias can occur post-CAR T-cell infusion, and they can occur either in the early phase or in the later phase after CAR T-cell infusion. Meaning that they can occur early within the first few days to weeks post-CAR T-cell therapy or could even occur months to years later. These cytopenias include anemia, thrombocytopenia, leukopenia, neutropenia. Many patients may present with fatigue, weakness, shortness of breath, lightheadedness, frequent infections, fevers, bruising, and bleeding, and the symptoms usually are consistent with how they would present otherwise with anemia, thrombocytopenia, or neutropenia. Acute cytopenias within three months of CAR T-cell therapy are more common. This is due to usually the lymphodepleting chemotherapy that is administered prior to CAR T-cell therapy. Most patients receive a combination of fludarabine and cyclophosphamide prior to CAR T-cell infusion, or they may receive another agent, such as bendamustine. Most patients also come into CAR T-cell therapy with low lymphocyte counts from previous therapies. Early cytopenias, as I mentioned, are generally due to lymphodepleting chemotherapy or other recent therapies. There also could be an immune-mediated process due to the CAR T-cells. Usually prolonged cytopenias which occur beyond three months post-CAR T-cell infusion can be seen in a small number of patients. And the mechanism of prolonged cytopenias is really unclear at this time, but likely multifactorial. Most recipients of CAR T-cells who have prolonged cytopenias beyond three months post-CAR T-cell infusion should have a standard workup to rule out other common causes, such as vitamin or nutritional deficiencies. They should also have testing such as bone marrow biopsy and scans to rule out relapse disease-- relapse lymphoma or leukemia, for instance, that could be causing these cytopenias. Other examples would be myelodysplastic syndrome or other bone marrow failure syndromes. So cytopenias are generally managed with supportive care including growth factor and transfusion support. This applies to both cytopenias in the early period post-CAR T-cell therapy or more delayed prolonged cytopenias. In patients who have prolonged cytopenias of unclear cause that could be immune-mediated, other interventions such as high dose IVIG or even steroids could be considered depending on the situation. For those that have cytopenias in the first few months post-CAR T-cell therapy, generally they are monitored and treated with supportive care, and these cytopenias eventually resolve in the majority of patients. BRITTANY HARVEY: Great. Those are important considerations. Then, Dr. Santomasso, what are the key recommendations regarding Hemophagocytic Lymphohistiocytosis? BIANCA SANTOMASSO: The major recommendations for the identification, evaluation, and management of Hemophagocytic Lymphohistiocytosis, or HLH-- this is also known as macrophage activation syndrome. First, let's just start by saying that this is a dysfunctional immune response, and it's basically characterized by macrophages which are revved up and hyperactive and also possibly lymphocytes as well. There are high levels of pro-inflammatory cytokines during this state and tissue infiltration, and hemophagocytosis, and organ damage. This can occur outside of the context of CAR T-cell therapy, either as a primary HLH or secondary HLH that can be either triggered by infections, or autoimmune disease, or cancer-- especially hematological malignancies, but HLH has also been observed as a rare complication of CAR T-cell therapy. And outside of the setting of CAR T-cell therapy, HLH is defined by fever, cytopenias, hyperferritinemia-- or high ferritin level-- as well as bone marrow hemophagocytosis. And what's interesting is that this is very similar to what's seen during Cytokine Release Syndrome, and that can make it difficult for patients who have moderate to severe CRS to distinguish that from HLH. The laboratory results may be very similar. So the key to recognizing HLH is really to have it on your differential even though it occurs rarely after CAR T-cell therapy. It may occur with slightly different timing and may require more aggressive treatment. The lab alterations can include, again, as I mentioned, these elevated levels of several cytokines, such as interferon gamma. We can't normally send those in the hospital or the clinic, but sometimes soluble IL-2 receptor alpha can be sent and serum ferritin can be sent, and that's an especially useful marker. There have been diagnostic criteria for CAR T-cell-induced HLH that have been proposed, and these conclude very high ferritin levels-- over 10,000-- and at least two organ toxicities that are at least grade 3, such as transaminitis, increased bilirubin, renal insufficiency or oliguria, or a pulmonary edema, or evidence of hemophagocytosis in bone marrow or organs. Unlike other forms of HLH that occur outside of the context of CAR T-cell therapy, the patients may not have hepatosplenomegaly, lymphadenopathy, or overt evidence of hemophagocytosis. So just because a patient may not show those yet doesn't mean that HLH shouldn't be considered. If we see patients that have a persistent fever without an identified infection source or worsening fever, we basically should be considering HLH and doing the appropriate workup and treatment. Patients with HLH often have low fibrinogen, high triglycerides, and also cytopenias as well. The treatment-- just as there's an overlap kind of in the signs and symptoms, the treatment and the clinical management overlaps as well with CRS, so tocilizumab is typically administered. But corticosteroids should really be added for these patients, especially if there's clinical worsening or grade 3 or greater organ toxicity. And if there's insufficient response after 48 hours of corticosteroid therapy plus tocilizumab, many centers consider adding another medication such as Anakinra. I'll finally make a comment that, outside of the context of CAR T-cell therapy, HLH is sometimes treated with cytotoxic chemotherapy, such as etoposide. This approach generally is not used as a first line for patients undergoing CAR T-cell therapy due to etopiside's documented toxicity to T lymphocytes. And generally, the corticosteroids, plus the anti IL-6 agent, plus Anakinra is considered the first line of management. BRITTANY HARVEY: Got it. That's an important note on the management of HLH, and a great note on distinguishing CRS and HLH. So in addition, Dr. Ghosh-- what are the recommendations for management of B-cell aplasia? MONALISA GHOSH: B-cell aplasia, it's a disorder that's caused by low numbers or absent B-cells. And this is particularly relevant to CD19 directed CAR T-cell therapy, which is what most of the CAR T-cell therapies that are available right now target. They target CD19, and CD19 is present on normal as well as malignant B-cells. So most patients who receive anti-CD19 CAR T-cell therapy will develop B-cell aplasia at some point, and B-cell aplasia may be temporary or prolonged. It usually does, on one hand, indicate ongoing activity of the CD19 CAR T-cells and can be used as a surrogate marker. And increase in CD19 CAR T-cells could, in some patients, signal impending relapse, or dysfunction, or absence of activity of CD19 CAR T-cells. B-cell aplasia in CAR T-cell recipients is really due to, as I mentioned, an on-target, off-tumor effect. It can be prolonged and there is variability in rates of prolonged B-cell aplasia. The most significant consequence of B-cell aplasia is that it can lead to low immunoglobulin production. And immunoglobulin production is a very important part of the immune response by providing antibody-mediated immunity, so patients may present with frequent infections and low immunoglobulin levels. For most CAR T-cell recipients, this can be managed with infusions of Intravenous Immunoglobulins-- IVIG. However, the presence of B-cell aplasia can also present other challenges-- especially during this current pandemic, as Dr. Santomasso alluded to earlier, that it is unclear if patients will be able to mount a sufficient enough antibody response to the COVID-19 vaccines available since they cannot produce significant amounts of antibodies. This is an active area of research. However, we do advise that all CAR T-cell recipients do get the COVID vaccine and also other seasonal vaccines, such as the influenza vaccine. So it remains to be seen. We need some more long-term follow-up studies on how many people who receive CD19-directed CAR T-cell therapy will have prolonged B-cell aplasia and what the consequences will be. At this time, it is suggested that patients have their IgG levels monitored and-- if possible-- their actual B-cell numbers monitored. And if their IgG levels drop below a certain number, then they may receive IVIG infusions intermittently. We recommend in this guideline using 400 as a possible cutoff for IgG levels prior to administering IVIG. However, if patients have higher IgG levels and they have recurrent or life threatening infections, infusion of IVIG is recommended as a consideration to help boost the antibody response. BRITTANY HARVEY: OK. As you mentioned, those challenges are particularly relevant now. So then, Dr. Santomasso, what are the key recommendations regarding Disseminated Intravascular Coagulation? BIANCA SANTOMASSO: Disseminated Intravascular Coagulation is a disorder that's characterized by systemic pathological activation of blood clotting mechanisms, which results in both clot formation throughout the body and also bleeding. There's an increased risk of hemorrhage as the body is depleted of platelets and other coagulation factors. So it's basically important for clinicians to be aware that DIC-- or Disseminated Intravascular Coagulation-- can occur after CAR T-cell therapy, and it can occur either with or without concurrent Cytokine Release Syndrome. The treatment is primarily supportive care and replacing the factors, such as fibrinogen-- based on the levels-- and also replacing factors based on partial thromboplastin time and bleeding occurrences. But corticosteroids and IL-6 antagonist therapy can be used if there is concurrent CRS or in the setting of severe bleeding complications. There is limited evidence for other interventions. BRITTANY HARVEY: Great. Appreciate you reviewing those. So then, the last category of toxicity addressed in this guideline-- Dr. Ghosh, what are the key recommendations for identification, evaluation, and management of infections? MONALISA GHOSH: So a variety of infections can be seen after CAR T-cell therapy. And there are many factors that can lead to infection after CAR T-cell therapy including the presence of cytokines, such as neutropenia or leukopenia and B-cell aplasia that we earlier discussed-- leading to low immunoglobulin production and protection. As well as the increased risk of infection due to use of high-dose steroids to treat CAR T-cell-related toxicities, such as ICANS or CRS. Early after the infusion of CAR T-cell therapy-- that is, within three months-- patients often develop neutropenia due to lymphodepleting chemotherapy and/or the CAR T-cells themselves. And these patients are particularly susceptible to infection, so most of the infections that occur early on tend to be bacterial infections, and a few fungal infections have been observed as well. Patients who receive high-dose steroids for high grade CRS or ICANS have been shown to have increased serious infectious complications including bacterial infections, fungal infections, as well as viral reactivations. Infectious complications that occur later are often due to hypogammaglobulinemia due to B-cell aplasia and reduced production of immunoglobulins. And treatment is typically directed at the infectious source, as it would be even if these patients did not have CAR T-cell therapy. There are some prophylactic antimicrobials that are recommended for CAR T-cell recipients who have prolonged cytopenias. Especially those with prolonged neutropenia should be on some sort of bacterial and/or fungal prophylactic antimicrobials. Patients should also be monitored for hypogammaglobulinemia long term and should receive intravenous immunoglobulins as needed. As we have mentioned a couple of times already, being very aware that these patients are also more susceptible to seasonal infection, such as influenza, is important, and so vaccinations are very important for this patient population. Vaccinating against influenza and vaccinating against COVID-19. BRITTANY HARVEY: Thank you both for reviewing those key points for the most common CAR T-related toxicities. So, just to wrap us up-- Dr. Santomasso-- in your view, how will this guideline impact both clinicians and patients? BIANCA SANTOMASSO: Well, I think we've seen now that cell therapy is really one of the major advances in cancer treatment in the past decade. And I think it's reasonable to expect more of these cell therapies to be developed, and we'll hopefully see their use extend beyond very specialized centers. But CAR T-cell therapy side effects are manageable if they're recognized, so I think this guideline helps that, and they're reversible with proper supportive care. They can be serious and they require close vigilance and prompt treatment. But, again, we believe this guideline and recommendations will help members of clinical teams with both the recognition and management of all of these toxicities, and that will help patients by increasing their safety. BRITTANY HARVEY: Great. That's important to note that these toxicities can be severe, but are also manageable. So I want to thank you both for your work on these guidelines and for taking the time to speak with me today, Dr. Santomasso and Dr. Ghosh. BIANCA SANTOMASSO: Our pleasure. MONALISA GHOSH: Absolutely. It was my pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events in patients treated with immune checkpoint inhibitors. To read the full guidelines, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

The Oncology Nursing Podcast
Episode 179: Learn How to Educate Patients During Immunotherapy

The Oncology Nursing Podcast

Play Episode Listen Later Oct 29, 2021 43:23


ONS member Kristi Orbaugh, RN, MSN, RNP, AOCN®, nurse practitioner for Community Hospital Oncology Physicians in Indianapolis, IN, and member of the Central Indiana ONS Chapter, joins Stephanie Jardine, BSN, RN, oncology clinical specialist at ONS, to discuss patient education prior to and during immunotherapy. This is a continued conversation from a previous episode that discussed findings from an ONS focus group that Orbaugh facilitated in August 2021; we've linked that in the episode notes. This podcast episode is supported by an educational grant from AstraZeneca. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.  Music Credit: "Fireflies and Stardust" by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0  Episode Notes  Check out these resources from today's episode:   NCPD contact hours are not available for this episode.  Oncology Nursing Podcast Episode 172: Address Knowledge Gaps in Evidence-Based Precision Medicine Care  Previous Oncology Nursing Podcast episodes on immunotherapy  ONS Voice article: New Patient Education Formats Help Nurses Connect Patients to Individualized Resources  ONS Voice article: Patient Education Is Critical to Managing irAEs for Immune Checkpoint Inhibitors  ONS Voice article: Tailored Education Improves Patient Satisfaction and Comprehension  ONS course bundle: Immuno-Oncology for the Oncology Nurse Case Studies  Immuno-Oncology Learning Library  American Cancer Society patient education resources   ASCO patient education materials  National Comprehensive Cancer Network guidelines on managing immunotherapy-related toxicities  To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. 

Electro Vessel
Electro Vessel 167 | Achilles

Electro Vessel

Play Episode Listen Later Oct 27, 2021 59:15


Electro Vessel is a weekly radio show distributed worldwide by Vessbroz. Each week the boys invite a guest to share the decks with them to showcase the very best in new and upcoming dance music from across the globe. The show has hosted artists like Nicky Romero, Timmy Trumpet, Julian Jordan, Vini Vici, Mike Williams, Swanky Tunes, Cat Dealers, DJ From Mars, and many more! The show also features the Track of The Future. The brothers each week select a promo or demo to play in the show they think will be big in the future. This week Vessbroz invited Achilles! Follow Achilles: https://soundcloud.com/achillesmusic 1. Vessbroz and Billy The Kit - Rise Again (Extended Mix) 2. Nick Endhem & Sixth Sense feat. Nito-Onna - Glow (Extended Mix) 3. Scorz & Diana Miro-Shadow 4. DEADLINE, CHOUJAA, ROBBIE HUTTON - Anymore 5. ASCO, SoNick - Distraction 6. Delirious (Extended Edit) 7. Valentino Khan - Deep Down Low (Sonic Snares & SOUNTEC Tribal Raw Edit) 8. Maddix - Different State 9 - VER:WEST vs. Morgan Page feat. Lissie - The Longest Road Before Sunrise (Achilles Mash-Up) 10 - ID - ID 11- ID - ID 12 - The Weekend vs. ID - Take My Breath vs. ID (ID Mashup) 13 - iio feat. Nadia Ali vs. Linka, Gregor Potter, EWAVE - Rapture vs. Reason (Achilles Mashup) 14 - Achilles - The Rhythm [RAVEUP] 15 - twoloud feat. Lena Sue - Don't Hesitate (Achilles Remix) [PLAYBOX] 16 - Armin van Buuren - Communication (Achilles Remix) 17 - Achilles - Touch Me This show is syndicated & distributed exclusively by Syndicast. If you are a radio station interested in airing the show or would like to distribute your podcast / radio show please register here: https://syndicast.co.uk/distribution/registration

ASCO eLearning Weekly Podcasts
Social Determinants of Health - Access to Care

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Oct 26, 2021 20:15


In this Social Determinants of Health (SDOH) episode, Dr. Deepak Vadehra (Roswell Park) moderates a discussion with Dr. Carmen Guerra (Abramson) and Dr. Daniel Carrizosa (Levine) on how access to care impacts SDOH and the available interventions and resources that can mitigate these issues for patients. View COI & Cancer.Net Podcast. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 10/28/2021

Cancer Stories: The Art of Oncology

A mother mourning the loss of her daughter discovers that she has lost something else important to her.   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. ELIZABETH CONROW: Access Denied, by Elizabeth Conrow. I lost my daughter, Amanda, in 2015. She was diagnosed with a brain tumor at age three and was in treatment for 2 and 1/2 years. Less than two weeks after she died, friends and family were getting on with their lives, but I was still in shock. I couldn't believe that Amanda was really gone. Early in the day, I looked at my kitchen table and tried to imagine her eating a bowl of rice, an unusual breakfast for a five-year-old. But that was Amanda. My eyes filled with tears as they rested on the empty chair. She was really gone. In that moment, standing in the kitchen, I struggled to remember every detail of who she was. It felt like the memory of her was slipping away. My heart beat quickened, and my mind raced with compulsive nagging thoughts. How tall was she the last time we were in the outpatient clinic? How much did she weigh? I realized I would never be able to put her on a scale again or mark her height on the cupboard door. I fear that this information would be lost forever, just like Amanda. I moved to my computer and started to log on to our hospital's online patient portal to see if I could find answers to my questions. How many times had I logged into this system looking for Amanda's test results or to message one of her doctors? How many times did it serve to confirm appointment times or remind me of medicine doses? I clicked the Sign In button, and my heart stopped. I couldn't get in. Instead of viewing her chart, I saw an alarming red stop sign and a message saying "access denied." I stared at the screen in disbelief. Just two weeks after losing my daughter, I faced yet another heartbreaking and unexpected loss. I no longer had access to Amanda's medical records. I no longer had a connection to her medical team and the hospital family I had grown to love and care for. Everything Amanda had been through for the last 2 and 1/2 years was gone. It was as if she never existed. She had vanished. I was caught off guard, deeply saddened, and utterly unprepared to have this connection to the hospital and this connection to Amanda ripped away. I was confused and embarrassed by my emotions. I certainly didn't need this access. But I was devastated that it had been taken away. I reached out to my daughter's oncologist to ask how and why the patient portal had been turned off. I let him know that it was really important to me to be able to view Amanda's records, at least for a time. It had never occurred to him that a parent might want to see this information again. He explained that it was a system designed safety measure that automatically turned off access to an account once a patient had died. I was the first parent to reach out to him with this question. Amanda's oncologist immediately contacted the online records office to reactivate her chart so I could search out answers to some of my questions. It brought me so much comfort to be able to go back in and revisit her medical journey. As I thanked her doctor, I shared with him how important it was to protect families from this type of trauma. I didn't want another family to experience this pain. He listened and helped put a manual reactivation system in place. Going forward when a child died, the online records office would manually reactivate each pediatric account individually. It wasn't a perfect solution, but it was a step in the right direction. It has been six years since Amanda's passing. I am now the bereavement coordinator at the same hospital where she received care. When I started in this role, I was surprised to learn of several families who, like me, had been denied access to their child's medical record. Hadn't the hospital resolved this issue years ago? I was frustrated that our institution hadn't found a better solution in the six years that passed. Last spring, as I followed up with bereaved families from our hospital, I had a conversation with a mother, Diane, that was hauntingly familiar and heartbreaking. Diane and I spoke on the phone shortly after the loss of her son, Evan. As we wrapped up our call, almost as an afterthought, she sheepishly asked about Evan's medical records being deactivated. I was immediately brought back to my kitchen table and the pain I felt when I experienced this secondary loss just two weeks after losing Amanda. I knew why Diane felt silly asking about this. And I deeply understood her need to log in. Diana explained that she was creating a record of everything Evan had been through, every transfusion, every chemo treatment, every inpatient and outpatient visit. And she could no longer complete that task. She shared her experience with me. I know for me, it was really difficult to wake up that very next morning, literally only about 12 hours since he died and not be able to look at it. Even though I know there had been no additional tests run since the last time I had checked, it was my morning routine to look at it. I would check it each morning, even before I got up. It had been that way for months while we were inpatient. First, looking at his ANC and counts, and then in the final month and a half, checking his bilirubin and liver numbers. There was always that hope that things were going to improve. This would be the day. So that first and subsequent time was just a blunt reminder that he was gone and there would be no more checking. I wanted to go back and look at his results, too. Oddly, I thought it would make me feel closer to him and closer to the routine I had while he was alive. Diane wanted to feel closer to her son. I wanted to feel closer to my daughter. Accessing a child's online medical portal is one way a parent begins to come to terms with this impossible loss. Snaman, et al, 2016, suggest that parents who are grieving significantly benefit from the creation and continuation of bonds with a child who has died. Revisiting a child's journey through the lens of the medical portal helps strengthen that bond. As I looked through Amanda's chart and remembered various times we visited the hospital, it helped me picture her more clearly. And it helped me feel a connection to her that I was deeply longing for. Looking through a child's medical record, while painful, can be part of healing and connection. In addition to creating bonds with a child who has died, the medical portal helps parents stay connected to the hospital and the medical team that cared for their child. According to additional research by Snaman, et al, 2016, bereaved parent's benefit from the ongoing support of a hospital throughout a time of grief. When a child dies, the secondary loss of the medical community can leave families feeling abandoned by those they have come to trust and depend on. Anyone who had taken care of Amanda felt like family to me. Sending messages to Amanda's medical team after she died provided a feeling of familiarity when everything else around me was spiraling out of control. A continuing connection with the medical team through the online portal can positively impact grief outcomes for bereaved parents. Accessing a child's medical record provides a grieving family with an easy way to communicate with, and ask lingering questions of the medical team. Access to medical records should not end when a child dies. The 21st Century Cures act acknowledges the need to provide patients with open notes and immediate access to medical information. As we implement real-time access for living patients, continuing access after a loss should also be considered essential. Dr. Alan Wolfelt, from the Center for Loss, discusses the need to say hello to one's grief and welcome it before saying goodbye to the person who died. In those early months, saying hello to grief meant reading through Amanda's medical records, communicating with her medical team, and uncovering every connection I had to her while she was alive. In some small way, logging into Amanda's medical portal and discovering that she was 42 inches tall and weighed 41.2 pounds brought me immeasurable comfort. As parents grieve the loss of a child, comfort and connection should be readily available without having access denied. SPEAKER 3: The guest on this podcast episode has no disclosures to declare. SPEAKER 4: Welcome to Cancer Stories, The Art of Oncology podcast series. With me today is Elizabeth Conrow, bereavement coordinator at the University of Rochester Medical Center and the author of Access Denied. Welcome to the program, Liz. ELIZABETH CONROW: Thank you so much for having me here. It's an honor to be here. SPEAKER 4: It is our pleasure. And first of all, let me start by saying I was very moved by the piece. And I'm so sorry that you lived through this experience. And really interested in knowing how you transformed your personal grief into now, your profession. ELIZABETH CONROW: Sure. Well, it's definitely been a process. Obviously, as a family, we never thought we would be down this road. I never thought I would have a child who had cancer. I never thought that I would have to go through the grief of losing a child and then comforting my own family, and my husband, and those around us through that experience. And I can tell you that for the first couple of years, I really didn't feel equipped to do anything. I felt like I lost my confidence in anything that I had an ability to do prior to this. Simple things like making a meal for someone who was sick became way too overwhelming to even consider doing. So it was definitely a process of years. But when the opportunity came up to work at Golisano Children's Hospital, the same place where Amanda had been cared for, the timing was right. And I knew that it was a great step to take and a way to honor Amanda's life, and really in some way, offer just a little bit of support and comfort to bereaved families, because I understood a little bit of what maybe they were going through. So it just seemed like a really good fit and a really good match for my experience at that point and a way to help and honor Amanda. SPEAKER 4: Let's start by talking a little bit about Amanda. Tell us a little bit about her and her story. ELIZABETH CONROW: Sure. Amanda is one of five children. So she was the fourth of the five. Very silly, loved to wrestle with daddy, had the biggest blue eyes that anyone had ever seen. She was just a delight and a joy. And when she was 3 and 1/2, she was diagnosed with a brain tumor. And we were in the hospital for a number of days. She had surgery and a full resection. And we were told that if after a resection and radiation it never came back, that we would be good. But that if it came back, it would likely be terminal. So we knew at the outset that this was-- we're not dealing with a cold or a headache. We're dealing with something pretty serious. So she went through the surgery beautifully. She went through all of her radiation treatments. We did a clinical trial of chemotherapy. And six months from when she was diagnosed, we really felt like we did well. She did amazing. And we were ready to walk away from everything and just celebrate really, kind of getting through this. And her very first follow-up scan two weeks after she was done with treatment-- her doctor, Dr. Koronas, called us and let us know the very devastating news that the tumor had returned, and it was all in her brain and down her spine and too many places to count. So six months from diagnosis, we knew that this was not going to end well. And we kind of had to struggle to prepare for that, as well as to recognize that in that moment, she was still Amanda. And she was still doing really well. But we knew that time would be limited. And so we had actually a very good year and a half with her, as much as you can say that. She went through additional radiation treatments. And we continued to try other chemotherapies to do what we could. But ultimately, in February of 2015, surrounded by her family in our home she passed away. And we then had a whole new struggle with grief and really, coming to terms with a new life and a devastating loss. But she was a joy. And she was a joy throughout it. So it was not all terrible. SPEAKER 4: She sounds like an extraordinarily little girl. And in your essay, you start by telling us that just after she died, I think a few days or weeks, you're thinking about her, and you want to access her medical record through the portal that you had gotten used to using all the time. And then as you're logging in, you get the signal that says "access denied." And that triggered a tremendous wave of grief for you or something. Tell us a little bit about that and what you did with that. ELIZABETH CONROW: Sure. I think I didn't realize at the time that I was really just trying to hang on to who she was, that I was trying to connect with her in some way. I mean, it was just two weeks after she had died. And I just-- I wanted access to see, what did she weigh? Goodness, if I could recreate her in the form of a stuffed animal, how long would she be? How much would she weigh? And when I went to log in, it was a horribly devastating loss. It really felt like all of the sudden, I knew in my mind she was gone, but logging into this wealth of information that contained all of her blood counts and numbers and information that we had access so often, to all of a sudden have that gone. It was just a punch in the gut reminder that she truly was gone and that her records had disappeared. And she just wasn't here. And I wasn't prepared for that. I really thought that I'd be able to go in and find the things I wanted to find and have peace about that. It was shocking to me. And I remember feeling so embarrassed like, how can I call her doctor and say, I lost this access and I really need it? When she's not here, there's no reason. I don't need it. He's going to think I'm crazy. But it was important enough to me that I reached out to him. And I said, you've got to help me. How can I still access this? SPEAKER 4: So what happened next? ELIZABETH CONROW: So he-- actually, I was pretty surprised. I was the first parent he said, that had ever reached out to him with this issue. And I thought, how is that possible? How is that possible? And I'm guessing other parents had experienced it, but didn't know what to do, didn't know where to turn. And he was very compassionate. And he reached out to our online medical team, our portal team, and tried to figure out a way to reactivate the account for me. And got that done very quickly. And I said, well, it's not enough that it's been reactivated for me. No other parent can go through this. We have to come up with a plan. And so he really did work very hard with our team here to come up with something that would hopefully fix the problem. And it did. I know many families then, had their access turned back on manually, through a manual process that they put in place here. But I know that in the last six years, there have been several families who went to log in and had this experience. And unless you've been there and unless you've been the parent on the end of losing a child and then going in and having more taken away that you didn't expect, you don't understand the pain of that. And so I think the driving force behind me really wanting to write this article was to say, I know that this isn't just my institution. I know this is happening across hospitals. I know that when a child dies, this access is turned off. And that really hurts families. And if there's a way to bring attention to that and say, hey, we can do better, we need to. SPEAKER 4: Now that you have this perspective, I know that you have actually developed some training for oncology fellows and staff to train them a bit to talk with bereaved parents. What are some of the lessons that you want people to learn? ELIZABETH CONROW: That's a great question. I'm working with another doctor here. It's an advanced communication training where we're helping young doctors share bad news for the first time. And it's amazing to me how afraid people are to approach the bereaved. And I guess, having been through it, I see now how poorly we really do bereavement and how afraid we are to kind of approach someone who's lost a child and just wrap our arms around them and say, I'm so sorry. I'm here with you. Everybody wants to fix it. And there's no fix. And people don't want to approach a bereaved parent and bring up their child, because they don't want to make them sad. And what many people realize is that our children are always on our mind. You're not reminding us of anything we're not already thinking about. I was pretty surprised after losing Amanda that someone could be on my mind all the time-- all the time when they're not here anymore. You know, you think about people here and there, time to time, people in your life. But once she was gone, she was right at the front of my mind and still is, every moment of every day. And so if you see a bereaved person, it's OK to mention their child's name. I actually-- I go to the dentist. And the woman who cleans my teeth, every single time I go, will mention Amanda. And I know it's intentional. And I know it's because she wants me to know that she cares. And so those kinds of simple acts that people do as a way of recognizing and honoring the child whose passed means so much to a bereaved parent. SPEAKER 4: Just listening to you and the emotion in your voice, I imagine it must have been difficult in a way to go back to the same place where Amanda was treated and now, work with the staff and the clinicians who treated her. Tell us a little bit about how you've managed those relationships? ELIZABETH CONROW: One of the things I've learned, and that's partly through the role I have now in supporting other bereaved parents is that everyone grieves differently. And I know there are some parents who, the first time they come back to the hospital, it's really, really hard for them. And it's almost like a PTSD moment. For me, I appreciated and cared about all of the medical staff so much that coming back here to me, was a need. I needed to get back here and find a way to connect with these doctors and nurses and the people who cared for Amanda so beautifully while she was here. In those first months of grief, I showed up at the hospital-- I remember there was one day I showed up, and I felt so lost. But I just needed to see those nurses and give them a hug. And I felt awkward and out of place, because suddenly, I'm here and she's not with me. But I just needed to be in a place where she had been and a place that meant so much to us. So coming back here for me, certainly had its hard moments. And there have been challenges with it. But it's been a place of comfort. And being able to talk about Amanda with other parents has really been a gift for me, because it's not an opportunity you have all the time, especially six years later to talk about the child who died. So it's been a gift. SPEAKER 4: What is it like for you to be with other parents now who are going through what you experienced? How does your experience of loss influence your role as a counselor for a newly bereaved parents? ELIZABETH CONROW: I do a lot of listening. I do a lot of listening. And there are some parents who I'll call and follow up with and check in on. And they're good. And they don't need anything. And to be honest, I think when we first lost Amanda, if someone called me and I had never met them before, I might say I'm good. I don't really need any support right now. I've got my family. But there are some parents who I will call, and they will talk to me for 45 minutes. And they will cry. And they will say, you're the first person I've been able to talk to about this, because you understand and you've been through it. And so I'm able just to listen. And when they say things that they think are crazy, I wandered into my son's room and I slept in his bed last night, I say, I understand that. I once found Amanda's socks in a travel bag. And when I found them, I pulled them out and I slept with her socks. So there are things that people think are crazy that I'm able to help them normalize some of those feelings and understand that it's OK. SPEAKER 4: I don't think it's crazy at all. You speak with such knowledge and also such empathy. I wonder if you can help us also understand how you see the clinicians now-- the doctors and nurses who are actually are caring for these patients-- how you see them react to the death of a patient and how they maintain their relationships with what the parents once the kids are gone? ELIZABETH CONROW: It's been very interesting, I guess you could say to be on the other side of this, right? I was on the parents side before, where I was able to receive kind of the love and comfort and support of those who cared for Amanda. And I was able to see them showing up at the funeral and the ways that they would reach out and send notes and cards. But now, being on this side working with many of those same people, I've been really struck, even during our weekly meetings when they talk about different cases and different families and the losses that they've had, how significantly it does impact them, and how much those families and those children really do mean to them. And you know, I've often sat there now wondering, well, what did they say about my family? What did they say about us? And not a conversation I can go back to and sit in on. But I'm just struck by how much they really do care and how much it extends beyond this just being a job for most of-- all of them. SPEAKER 4: Yeah, in your role now, in your professional role, what kind of changes have you implemented in the way clinicians and parents communicate, or the way the system communicates with parents? ELIZABETH CONROW: At our hospital where I work, we have probably around 80 or 90 losses a year. And I came into this and said, I can support these families. And I can follow up with 80 or 90 families in a reasonable manner. But really, we need more parents doing this. We need to expand kind of what we're doing. So I've been trying to work toward implementing a mentoring program of sorts, where bereaved parents who are a few years out in their grief can come alongside newly bereaved parents and really support them, one on one for a year or a year and a half to help them get through that time, so that it isn't just me. And as great as I am, I really know that we can do much, much better by parents if we expand kind of the support network that we have. So I've been trying to grow some of our bereaved parent base. And those who can give input on some of the things we're doing-- because I know bereaved parents have so much wisdom and so much they can share from their own experiences. SPEAKER 4: You sound like a force. I wonder, have you connected with other hospitals, other teams? Or is your-- are you concentrated on your hospital and your community? ELIZABETH CONROW: The greatest support to me, actually has been St. Jude. They have such a fantastic program. Their bereavement, their parent support is really outstanding. Actually, just this week, I was able to sit in on one of their parent mentor trainings to kind of learn, well, how do you train your people, and what do you do? And so that was fantastic. So I'm really grateful-- grateful for their support. So they've been really wonderful. SPEAKER 4: I imagine Amanda's passing really affected your entire family and the other kids. Can you tell us a little bit about how all the other kids dealt with their grief? ELIZABETH CONROW: Sure. I know at the time when Amanda was diagnosed, my oldest was 9, and my youngest was 9 months. So everybody was pretty little. And they went through that at a really young age. And then when she passed, my oldest was 11 and my youngest was 3. So they were still little. And they had been through what I consider to be significant trauma in those early years. And when things first happened, I mean, I had a therapist describe it to me as a children's mobile that hangs over their bed you know, that once it becomes imbalanced, it just tips on its side. And that's the way things felt at home for quite a while. You know, just nothing felt right and things felt out of order. But kids are so resilient and so forward looking. And my kids really did beautifully through it. And I had someone tell me, well, kids are going to revisit grief. And they're going to come back to it from time to time. And it'll surprise you. And I will say, that's so true. You know, I would think everything was going along OK and everyone was coping well. And then, my daughter Jessica, who was closest in age to Amanda, would come down at 10 o'clock at night in tears because she was thinking about her sister. And that would catch me a little bit off guard. And my oldest just went away to college. And she's now 18. And she's had some conversations with me lately just about everything they went through and really revisiting some of her feelings about it all. And so they don't really get over it. But helping them to kind of process it and work through it and really, just talk about her. We talk about her constantly. She's a part of everything we do. We still make her a birthday cake. So we just keep her memory alive and celebrate her life together. But grief for kids is certainly different, and it doesn't end. But they are definitely forward looking and really can handle more than I think sometimes we give them credit for. SPEAKER 4: And your husband and you I hear have also been involved in some activities to talk about this publicly or teach others. What was that like for you as parents? ELIZABETH CONROW: There are a few things that we've really wanted to help move forward in terms of childhood cancer awareness and things that people can do to really help bereaved parents. And I think there's just so much that people don't know or understand. Many people don't realize how underfunded childhood cancer is. So it just means a lot to us to be able to kind of get that message out now. SPEAKER 4: I imagine there's so much work to do. And as we've had this great opportunity to chat about Amanda to remember her, to think about your experience and the amazing work you seem to be doing-- are there any final comments that you want to share with our listeners? ELIZABETH CONROW: It's an honor for me to really share this experience. And that bereaved parents need support, and they need to know that people care and remember, even as time goes on. So just take good care of those who know who are grieving. And love one another. SPEAKER 4: Thank you so much. This is Liz Conrow, author of Access Denied, published in Journal of Clinical Oncology. Thank you very much. Until next time. SPEAKER 1: Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. [MUSIC PLAYING]

Journal of Clinical Oncology (JCO) Podcast
Is Dose-Adjusted EPOCH-R the Optimal Treatment for Children with Primary Mediastinal B-Cell Lymphoma?

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Oct 20, 2021 8:30


This podcast will discuss data from a phase II trial evaluating the dose-adjusted EOPCH-R chemo-immunotherapy regimen for the treatment of primary mediastinal B-cell lymphoma in children.   TRANSCRIPT [MUSIC PLAYING] LISA GIULINO-ROTH: This JCO podcast provides observations and commentary on the JCO article "Dose-Adjusted Rituximab Therapy in Children and Adolescents with Primary Mediastinal B-cell Lymphoma, a Multicenter Phase II Trial" by Burke et al. My name is Lisa Giulino-Roth, and I am a pediatric oncologist at Weill Cornell Medical College in New York. My oncology specialty is lymphoma in children, adolescents, and young adults. I have no relevant disclosures. Primary mediastinal B-cell lymphoma, or PMBCL, is an aggressive non-Hodgkin lymphoma derived from thymic B-cells. While previously classified as a subtype of diffuse large B-cell lymphoma, PMBCL is now recognized as a distinct clinical and pathologic entity. Unlike diffuse large B-cell lymphoma, PMBCL has a peak incidence among adolescents and young adults and is more common in females. PMBCL also shares many molecular characteristics with Hodgkin lymphoma, including alterations in JAK-STAT pathway signaling and amplification of the 9p24.1 locus, leading to upregulation of PD-L1. Adults with PMBCL have historically been treated on regimens designed for diffuse large B-cell lymphoma, which in the US was most commonly R-CHOP and radiation therapy. More recently, adult patients have been treated with a dose-adjusted EPOCH-R regimen, which is composed of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab. This radiation-free approach is of interest, given this young and predominantly female population who are at risk for significant long-term toxicity from chest radiation. In a single center NCI-led study by Dunleavy and colleagues, dose-adjusted EPOCH-R was administered for six to eight cycles without radiation therapy and resulted in excellent outcomes with a five-year event free survival of 93% and overall survival of 97% among 51 adult patients. Pediatric patients with PMBCL have historically been treated on regimens designed for mature B non-Hodgkin lymphoma, which in pediatrics is most commonly Burkitt lymphoma or diffuse large B-cell lymphoma. These dose intensive multi-agent regimens include doxorubicin, high dose methotrexate, and intrathecal chemotherapy without radiation. Outcomes for children with PMBCL treated on these regimens are inferior to pediatric patients with diffuse large B-cell lymphoma treated on the same protocol. Children with PMBCL have a five-year event-free survival ranging from 65% to 75% in different international series. Given the excellent outcomes observed with dose-adjusted EPOCH-R in the adult NCI trial, an international phase II trial of this approach was conducted by two cooperative groups, The European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children's Oncology Group. This single arm trial enrolled patients age 18 and under with primary mediastinal B-cell lymphoma. All patients were treated with six cycles of dose-adjusted EPOCH-R without radiation. The primary endpoint was event-free survival with events defined as any of the following-- viable cells in any residual mass after six cycles of treatment, relapse, progressive disease, secondary malignancy, or death from any cause. The four-year event-free survival from this trial would be compared with the event-free survival from historic controls, which was estimated at 67%. A total of 46 pediatric patients were enrolled between 2012 and 2016. All patients received six cycles of dose-adjusted EPOCH-R without RT. At a median follow-up of 59 months, there were 14 events, including four patients with viable cells in the residual mass at the completion of therapy, eight progressions or relapses, and two secondary malignancies, including one case of Hodgkin lymphoma and one case of acute promyelocytic leukemia. The event-free survival of the entire cohort at four years was disappointing at 69.6% with a 95% confidence interval of 55.2% to 80.9%. This was not statistically different than historic controls treated on pediatric mature B and HL regimens. Overall survival at four years was 84.8% with a 95% confidence interval of 71.8% to 92.4%. The authors acknowledge several limitations in the current study and challenges when comparing this study to the NCI trial. Not all patients adhered to the dose escalation rules, and 29% should have received a higher dose level in at least one course of treatment. Among the 10 cases of local relapse or primary refractory disease, five were noted to have a failure to dose escalate, including one patient with a clinical complication that precluded dose escalation. Comparing this trial to the NCI trial is challenging due to several important differences. Adults in the NCI trial were treated with six or eight cycles of dose-adjusted EPOCH-R based on the response between cycles 4 and 6. In pediatrics, eight cycles was not deemed appropriate, given the potential for greater than 600 milligrams per meter squared of cumulative doxorubicin exposure and concern for significant long-term cardiac toxicity at this exposure level. In addition, the NCI trial did not consider residual viable cells or secondary malignancy as an event, both of which were defined as events in the current pediatric trial. In a reanalysis of the pediatric data using the NCI event definitions, there was only a modest change in event-free survival with a four-year event-free survival of 73.9%. So where does this leave dose-adjusted EPOCH-R and the management of pediatric patients with PMBCL? In my opinion, there's no single superior regimen to treat pediatric PMBCL. Outcomes are similar across regimens. However, the toxicities are different. Dose-adjusted EPOCH-R offers significantly less short-term toxicity, but the potential for a higher cumulative doxorubicin dose compared to pediatric mature B and HL regimens. Regardless of the chemotherapy backbone, it is clear that for children with PMBCL, outcomes remain suboptimal, and further studies are needed to advance treatment. Given the rare nature of PMBCL and the peak incidence in the AYA population, combined pediatric and adult trials may allow us to evaluate novel agents and advance outcomes. Both children and adults with PMBCL may benefit from the incorporation of novel agents. Retrospective multicenter data from adults treated with dose-adjusted EPOCH-R have also failed to reproduce the excellent outcomes observed in the NCI trial. In two large retrospective series, adults with PMBCL treated with dose-adjusted EPOCH-R had a two- and three-year progression-free survival of 85% and 87% respectively. To advance outcomes in PMBCL across age groups, our team at the Children's Oncology Group in collaboration with Alliance and the National Clinical Trials Network is conducting a randomized phase III trial of the checkpoint inhibitor nivolumab in combination with chemo immunotherapy for adult and pediatric patients with PMBCL. Checkpoint inhibitors, including pembrolizumab and nivolumab, have demonstrated efficacy and PMBCL in the relapsed setting. And pembrolizumab is FDA approved for children and adults with relapsed PMBCL after two or more lines of therapy. However, these agents have not been evaluated in the upfront setting. In this trial, the treating physician will choose between R-CHOP and dose-adjusted EPOCH-R as the chemotherapy backbone. And patients will then be randomized to standard of care with six cycles of chemo immunotherapy alone or six cycles of nivolumab plus chemo immunotherapy. We are optimistic that this will define the role for checkpoint inhibition in the upfront management of PMBCL and work towards improved outcomes for both adult and pediatric patients. This concludes this JCO podcast. Thank you for listening. [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.

ASCO eLearning Weekly Podcasts
Cancer Topics - New Therapies for Lymphoma (Part 1)

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Oct 15, 2021 26:53


In part one of this two-part ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of recently approved therapies for diffuse large B-cell lymphoma through examination of challenging patient cases. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 10/20/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] SONALI SMITH: Hello, and welcome to this episode of the ASCO Education Podcast highlighting new therapies for lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical investigation in lymphoma. I'm also the Elwood V. Jensen Professor and chief of the hematology/oncology section at the University of Chicago, and very excited to be joined by my colleague, Dr. Paolo Strati. PAOLO STRATI: Good morning to everybody. My name is Paolo Strati. I'm a hematologist and medical oncologist and an assistant professor in the Department of Lymphoma/Myeloma, and in the Department of Translational Molecular Pathology at MD Anderson Cancer Center, Houston, Texas. And I'm also the clinical director for the Lymphma Tissue Bank. In part one of this podcast episode, we will discuss the adoption of recently approved therapies for diffuse large B-cell lymphoma, such as selinexor, tafasitamab, Liso-Cel, and Lonca-T. These therapies have transformed care for patients with this disease. And we'll start our conversation today with a patient case. SONALI SMITH: Great. Well, I'll go ahead and present a patient to you, Paulo. So this is a 78-year-old man with diffuse large B-cell lymphoma that is the germinal center-derived subtype. It is not double expressor, it is not double-hit. He has advanced stage disease with a high IPI, as well as the high CNS IPI. Luckily, his performance status is zero and he has no significant comorbidities or other health conditions. He received frontline dose-adjusted EPOC-R with intrathecal methotrexate for six cycles. But at the end, he had a partial remission. So how do you select your salvage therapy in this situation? Are you concerned about using agents targeting CD19 in the second line, given the potential need to use anti-CD19 cellular therapy, or CAR-T in the third line? PAOLO STRATI: This is a very interesting and unfortunately not uncommon case. And thank you, Sonali, for asking these very important questions. Technically, a platinum-based regimen followed by autologous transplant will be a standard answer and may be feasible. Because as you mentioned, this patient has a good performance status and non-meaningful comorbid health conditions. However, patients who are refractory to a frontline anthracycline-based regimen, such as in this case, with achievement only of partial remission at the end of frontline dose-adjusted EPOC, can potentially experience a suboptimal outcome following the standard approach with a platinum-based second line regimen. And as such, alternative strategies may be needed. To this regard, the combination of tafasitamab that, as you know, is a monoclonal antibody targeting CD19, and lenalidomide, an oral immunomodulatory agent, a combination which is currently approved by the FDA in the United States as a standard second line option for transplant ineligible patients, would be a great option in this case. Data from the three year follow-up of the phase II study that has brought to the FDA approval this combination, the L-MIND had been recently presented and have showed the complete remission rate of 40% and immediate duration of response of 44 months, including patients who received this regimen as a third line or beyond. So there is, of course, a biological concern by targeting CD19 in second line. These may potentially impact a third line use of an autologous anti-CD19 CAR-T, because CD19 downregulation may potentially be a mechanism of escape to tafasitamab. And recent data has shown the CD19 levels are strongly associated with the efficacy of CAR-T cell therapy in patients with large B-cell lymphoma. Small retrospective studies have shown that autologous anti-CD19 CAR-T can be safely and effectively used after antibodies or antibody drug conjugate targeting CD19. But we need a significantly larger and prospective data, including serial tissue biopsy in these patients before considering this combination as a standard practice in patients for whom we plan to use CAR-T as a third line. Until then, I would be cautious in using second line tafasitamab in patients, again, for whom there is a potential plan for anti-CD19 autologous CAR-T in third line. And if necessary, limited to very selective cases. Finally, recent press releases have anticipated the two autologous anti-CD19 CAR-T products, Axi-Cel and Liso-Cel, are superior to autologous settings transplanted in second line. And so in the near future, CAR-T cell therapy may become a standard second line option. And that would be an ideal option in primary chemorefractory patients as the case that you presented here. SONALI SMITH: Yeah, I agree. There are a tremendous number of options. And having anti-CD19 products as well as autologous stem cell transplant, the sequencing will be an evolution. So going back to this patient, he received tafasitamab and lenalidomide for two cycles with no significant toxicity, but unfortunately, he had further progression after two cycles based on a PET/CT scan. So what are your next steps? Would you move directly to an autologous anti-CD19 CAR-T cell therapy now? Would you re-biopsy before that? And how would you select among the three available CAR-T products? PAOLO STRATI: These are not easy questions, particularly the selection of one out of three available CAR-T products. As you said, there are currently three autologous anti-CD19 CAR-T products approved by the FDA in the United States for the treatment of large B-cell lymphoma in third line or beyond. And these are Axi-Cel, Tisa-Cel, and Liso-Cel. For all of them, the best outcome is observed for patients who have a low turmor burden at time of CAR-T infusion. And they need to either select patients with no bulky disease or to decrease it through bridging therapy. And as we define bridging therapy given between leukapharesis and CAR-T infusion. Unfortunately, there is currently no standard bridging therapy and all FDA products approved in third line can potentially be used in this specific scenario that you described, including polatuzumab with bendamustine/rituximab, selinexor, and Lonca-T, of course, beyond tafasitamab and len that has already been used in this case. Of course, when selecting a bridging therapy, there are many disease-related and patient-related factors to take into consideration, including the need to preserve the host immune microenvironment that we all know is crucial for the subsequent activity of CAR-T cells. And also, we need to give into consideration the need to preserve as much as possible, as we discussed previously, in CD19 expression. To this regard, and going back to one of your questions, I strongly recommend to re-biopsy patients if any bridging therapy is used between bridging therapy and CAR-T infusion in order to document CD19 expression before CAR-T infusion. When it comes to CAR-T product selection, as I said, it's a really difficult decision to do. And we don't have at this time randomized trials in third line. And as such, the decision is really left to the treating physician based on multiple factors. But all of the limitations of inter-study comparison, efficacy seems to be pretty much the same for the two products, maybe slightly higher based on the recent second line data. But Axi-Cel and Liso-Cel as compared to Tisa-Cel, and also as suggested by recent press release. However, due to the fact that Liso-Cel and Tisa-Cel have less potent co-stimulatory domain for 1BB instead of CD28, the rate of CRS and ICANS, the two main toxicities associated with CAR-T cell therapy, is usually lower with this to the point that some centers are able to infuse them in the outpatient setting, whereas Axi-Cel is almost always infused in the inpatient setting so the toxicity can be monitored more closely. So with older patients or those who have comorbid health condition, Tisa-Cel and Liso-Cel may be a safer option, though there's a lot of research going on trying to mitigate toxicities associated with Axi-Cel. Finally, it's important to keep in mind manufacturing time. Axi-Cel is manufactured in an average of 17 days, whereas Tisa-Cel and Liso-Cel take typically longer than three to four weeks. This can be itself a determining factor, particularly for patients who are quickly progressing and where immediate treatment is needed. SONALI SMITH: Yeah, I agree. I think there are going to be many patient product and disease-based factors that will impact both the effectiveness as well as the toxicity. And you did a really great job of explaining the role of the co-stimulatory domain potentially in some of that, as well as all of the products that are out there. It's definitely a complicated area. Going back to our patient, so he did undergo leukapharesis for Liso-Cel and received third line polatuzumab and rituximab without bendamustine. The restaging PET/CT after two cycles showed a PR with a significant decrease in tumor burden, and repeated biopsy showed high expression of CD19 by flow cytometry. He then proceeded with Liso-Cel, which was relatively well tolerated. There was only grade 1 cytokine release syndrome and no ICANS, so no neurotoxicity. And his day 30 PET/CT showed a complete remission. Unfortunately, the 90 day PET/CT showed progression. So Dr. Strati what is the outcome for patients who relapse after CAR-T? Do you recommend to re-biopsy? And what are the efficacy data for FDA approved agents for these patients? And I know this is a long question, but is there any role for repeated CAR-T or allogeneic transplant now? PAOLO STRATI: Unfortunately, currently, the outcome of patients with large B-cell lymphoma relapse or progress after autologous anti-CD19 CAR-T is suboptimal, with a life expectancy, unfortunately, shorter than six months. Hence, the need to be creative and customize treatment based on biological data. To this regard, I think it's crucial to repeat a tissue biopsy to guide subsequent therapy. As mentioned previously, there are currently four products approved by the FDA for patients with large B-cell lymphoma in third line and beyond. Two of these target CD19, tafasitamab plus lenalidomide and Lonca-T One targets CD79B, polatuzumab combined with bendamustine and rituximab. And one is an SPO1 inhibitor, selinexor. While we have no data for selinexor in patients who relapse or progress after CAR-T cell therapy, limited prospective data showed that a progression-free survival in the order of weeks is usually observed for patients who receive polatuzumab with or without bendamustine and rituximab after CAR-T cell therapy. So I would not recommend that. However, there's some interesting activity in the post-CAR-T setting for Lonca-T and for tafasitamab/len is limited to patients who still express CD19 in time of relapse. And of course, it needs to be largely and prospectively further investigated before becoming a standard approach for patients who relapse or progress after CAR-T cell therapy. When it comes to cellular therapy, repeated anti-CD19 CAR-T infusion is not shown to be successful in the original registration studies. So it is not currently something that I would recommend and is not definitely a common practice. And very limited retrospective studies have shown the use of allogeneic stem cell transplants in the post-CAR-T setting may be associated with quite elevated treatment-related mortality. So I don't suggest this as a standard practice in large B-cell lymphoma at this time. This is different from B acute lymphoblastic leukemia, where instead, allogeneic stem cell transplant is becoming progressively a standard approach. And we definitely need more data before using this consistently. While we strive to identify the optimal cell batch therapy for large B-cell lymphoma patients who relapse or progress after CAR-T cell therapy. I think the priority should be given to clinical trials, including CAR-T targeting molecules other than CD19, such as CD20, CD22, CD79B, allogeneic CAR-T there are immediately available, so without the need to wait for manufacturing times. And K-CAR, that may be less toxic than CAR-T and other non-cellular therapy biological agents. So definitely, clinical trials are, at this time, the best approach in patients who relapse after CAR-T cell therapy, as the case that you described. SONALI SMITH: Thank you Dr. Strati. As an update, this patient had repeated biopsy showing a CD19 positive relapse. He consented for a clinical trial with a novel NK-CAR targeting CD19, achieving CR which is still ongoing at nine months. And this case really does represent some of the most exciting advances that we've had for this disease for patients who can tolerate aggressive therapies and have access to clinical trials. PAOLO STRATI: Dr. Smith, I'd like to hear your opinion about another patient with diffuse large B-cell lymphoma. This patient is an 81-year-old man with a history of coronary artery disease and well-controlled diabetes mellitus, who noticed a right cervical lymph node while shaving that seemed to have popped up. He was evaluated by his primary care physician and given a course of antimicrobials. 10 days later, the lymphoma seems to be enlarging and he is referred to ENT pharyngeal biopsy. The specimen is small but shows follicular lymphoma in a portion of the sample. However, there is also concern for larger cells and possible transformation. The patient is also beginning to note night sweats and a decreased appetite. And labs are notable for elevated LDH, 500, and thrombocytopenia with a platelet count of 110. So Dr. Smith, in your opinion, is this specimen sufficient to start treatment? Or should treatment be delayed to get a larger and maybe excisional biopsy? SONALI SMITH: Yeah, thank you for this question. I think this is a challenge we have in the clinic all the time, which is what is a sufficient biopsy specimen to make a diagnosis that allows us to subtype lymphoma? As we know, every lymphoma subtype, the treatment is really guided by the histology and not so much the stage or some other factors. So having a needle biopsy is unfortunately often insufficient. In this case, we have a very strong concern for a possible transformation. And as we know, both follicular lymphoma and diffuse large B-cell lymphoma can mark very similarly when it comes to immunophenotype. Certainly, the germinal center type of diffuse large B-cell lymphoma or any transformed follicular lymphoma will be CD20 positive, CD10 positive, and it really requires architecture to be able to tell whether or not there are sheets of large cells. So the ideal outcome for this patient would be to have a biopsy that is done promptly that allows us not only to confirm whether or not there is histologic evidence of transformation, but also to conduct FISH studies to determine if there's acquisition of a MYC rearrangement. At its core, all follicular lymphoma patients essentially have a transformation of 14;18, leading to BCL2 rearrangement and BCL2 overexpression. During the transformation process, there can be an acquisition of a MYC rearrangement, which would then make this a double-hit lymphoma and certainly has a much worse prognosis and may also prompt a change in treatment if the patient can tolerate more intensive therapy. So my recommendation would be to have a biopsy. Now one other aspect is that sometimes, we don't really have the time to proceed with a biopsy, or the lymph node may be in an inaccessible area. And in that case, there are some other criteria that we can use to assume that somebody has a transformation. Symptoms such as profound B symptoms and elevated LDH, and sometimes, a PET scan with multiple areas of very high avidity, can lead you to feel or suggest that this person has a transformation. There is some controversy over the use of PET and we know it does not confirm a diagnosis of transformation. But in my opinion, this is very suggestive if there are many areas of high SUV. PAOLO STRATI: Thank you, Dr. Smith. I agree completely about the importance, when time allows, to perform either a larger core biopsy or an excisional biopsy, because as you very well-outlined, this has not just a mere diagnostic purpose, but can meaningfully affect treatment planning for patients. And actually, in this case, as you suggested, the patient eventually had multiple core biopsy that showed transformed follicular lymphoma with very evident areas of diffuse large B-cell lymphoma. FISH, as expected for follicular lymphoma, was positive for translocation for TN18, but luckily negative for MYC rearrangement. So fortunately, we didn't have to deal with a double-hit lymphoma. The remainder of his staging showed he had diffuse lymphadenopathy. And PET scan, as you mentioned, has a controversial role in the diagnosis of transformation. So there's some areas that had high avidity with an uptake with an SUV of 1215, whereas other areas were less intense with SUV 618. And usually, heterogeneity in SUV actually helps further supporting diagnosis or transformation. While meta-maps showed follicular lymphoma, no large cells. So movement was isolated in the B-cell lymphoma. So Dr. Smith, at this point, based on the provided information, what's your treatment approach in this older patient and also a patient with comorbid health conditions, but with diffuse large B-cell lymphoma? SONALI SMITH: Yes. The goal of treating any aggressive lymphoma is to obtain remission, and if the remission lasts, to hopefully offer cure to the patient. And when somebody has a transformed lymphoma, of course, there is a dual concern, which is that the aggressive component can potentially be put into remission in a durable way achieving cure. But the indolent component will always need to be monitored, although hopefully, will not be life threatening the way the aggressive component can be. Treating an octogenarian is really challenging, particularly due to comorbidities in this age group and the potential toxicity of chemotherapy. So the standard of care for diffuse large B-cell lymphoma is anthracycline-based chemotherapy. But this, of course, can have significant toxicity in older patients. And in addition, the vincristine can aggravate neuropathy. And I've personally found that the high dose steroids that are part of CHOP can also cause toxicity in older patients and patients who are frail. So unfortunately, the literature is somewhat sparse. But we do have several data sets that can guide management in this particular patient situation. The French published, over a decade ago, the development of R mini CHOP, that includes an attenuated dose of cyclophosphamide, doxorubicin, and vincristine, and leads to some durable remissions and cure. Unfortunately, the long-term overall survival is less than 50% with R mini CHOP. And so although this is an appropriate backbone, there's certainly a lot of room for improvement. And there's also toxicity even with R mini CHOP. So in their initial phase II trial, there was actual deaths related to the R mini CHOP, particularly in the first cycle or two, really necessitating some type of pre-phase help ease patients into the chemotherapy. One of the challenges that we face in the clinic is that when we meet an older patient, we both want to maximize our chance for cure, but also minimize the toxicity that is particularly pronounced. And there is very little data in terms of how to guide this at the bedside. I'm excited that SWOG, with the US Intergroup, is conducting a trial, S1918, which prospectively includes a frailty assessment tool that was developed by the Italian group in lymphoma, and then also includes serial comprehensive geriatric assessment so that we can get a better idea about quality of life both during and after treatment. So there is no great standard of care right now, but I would say that R mini CHOP, outside of a trial, is a very reasonable way to proceed. PAOLO STRATI: Dr. Smith, thank you for outlining so well what we can do to minimize toxicity and to better select patients for this type of treatment. And as an Italian practitioner in the United States, I am very excited that the Italian frailty tool will be used in this SWOG trial. Are there any other ways to further improve safety when we use chemo immunotherapy in older patients or patients with comorbid health conditions? In particular, there is a lot of concern about potentially infectious complications in these patients. And so I'm wondering if there's any routine antimicrobial prophylaxis that you recommend. SONALI SMITH: Yes. I think it's really important to maximize supportive care for our older patients with aggressive lymphomas getting intensive therapy. I did mention the pre-phase, and I would just like to mention that one more time because I do think there's data that providing a brief pre-phase can minimize toxicity with the first cycle. And how this pre-phase is given is highly variable. Again, the data is somewhat limited, but it typically includes steroids given for five to seven days with or without a dose of vincristine. And steroids themselves can have toxicity. And the dose of the steroids, I think, is somewhat controversial. In my personal practice, I use somewhere between 40 to 60 milligrams per day for five to seven days. And I do not typically use vincristine, although a prospective French trial recently did and showed that this significantly improved toxicity. Other complications that can occur really are related to infection. And so, of course, all patients should have growth factor support as per ASCO guidelines. But I also routinely give VZV prophylaxis with acyclovir or valacyclovir. And for the first cycle in particular, I have patients come back to clinic after the first dose one week later to ensure that the counts are stable and that they are doing well. This is really where our team of nurses and other providers who are part of the care team are so important and communication is also very important. PAOLO STRATI: So Dr. Smith, as you suggested, also, this patient actually received mini R-CHOP without any complications. And end-of-treatment PET/CT can showed a VL score of 3, so a complete metabolic remission, potentially. How do you interpret these findings? SONALI SMITH: So response criteria in clinical trials, and then of course, extrapolated to the clinic, have evolved in lymphoma. And the Deauville or the International Prognostic Scoring System that has been used typically defines a uptake relative to liver and mediastinal blood pool. And those patients who have a Deauville 1 to 2, which is less than that bar, is considered negative. And 4 to 5 is positive, with five being the emergence of new sites of adenopathy. The interpretation of a Deauville 3 can be somewhat more complicated, but this really outlines the limitations of just using the SUV or the PET scan uptake to measure response. For my patient and for this patient, the lymph nodes all substantially decreased in size. And having some type of combined interpretation of the uptake, as well as the size that has decreased, I think is going to be a very important part of how we approach patients going forward. So for this patient, I opted for close observation after the completion of therapy and felt that his Deauville 3, along with the decrease in the size of the lymph nodes, was very significant. PAOLO STRATI: I completely agree with that. Where PET scan is an extremely helpful tool, particularly for the management of aggressive B-cell lymphoma, can also become a major challenge when it comes to its interpretation for these borderline scenarios. And as you said, it's very important to add into the equation multiple parameters, including CT findings and overall patient performance status symptoms. So that's all we have for today. Thank you, Dr. Smith. This was a great conversation. We have learned and discussed a lot about diffuse large B-cell lymphoma, including novel biological agents, CAR-T cell therapy, management of elderly patients, and patients with comorbid health conditions and interpretation of PET/CT scan. I think this will be very helpful. And the conversation will continue beyond this podcast. In part 2 of this episode, airing in November, we will discuss new therapies for mantle cell lymphoma and for follicular lymphoma. Thank you so much to all the listeners tuning into this episode of the ASCO Educational Podcast. SONALI SMITH: Thank you. It's been a pleasure to speak with you today. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

Research To Practice | Oncology Videos
Lung Cancer | Expert Second Opinion: The Emerging Role of Immunotherapy and Targeted Treatment in Localized Non-Small Cell Lung Cancer

Research To Practice | Oncology Videos

Play Episode Listen Later Oct 14, 2021 57:36


Featuring perspectives from Drs Edward Garon, Jarushka Naidoo, Harvey Pass and Heather Wakelee, including the following topics: Immunotherapy in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC) Introduction: Tumor board discussions since ASCO 2021 (0:00) Case: A woman in her early 60s with Stage IIA lung adenocarcinoma — PD-L1-negative, pan-wild type (8:00) Case: A man in his mid-50s with Stage IIA squamous NSCLC — PD-L1 15% (22:44) Case: A man in his early 90s with Stage IB lung adenocarcinoma — PD-L1 10% (31:47) Key relevant data sets (39:07) Adjuvant Treatment of NSCLC with a Driver Mutation Case: A man in his late 60s with Stage III lung adenocarcinoma — PD-L1

ASCO eLearning Weekly Podcasts
Oncology, Etc. - In Conversation with Dr. Otis Brawley (Part 2)

ASCO eLearning Weekly Podcasts

Play Episode Listen Later Oct 5, 2021 19:40


In the second edition of this two-part Oncology, Etc. episode, hosts Dr. Patrick Loehrer (Indiana University) and Dr. David Johnson (University of Texas) continue their conversation with Dr. Otis Brawley, a distinguished professor of Oncology at Johns Hopkins and former Executive Vice President of the American Cancer Society. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us Air Date: 10/5/2021   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DAVID JOHNSON: Welcome back to Oncology, Etc, and our second segment of our conversation with Otis Brawley, professor of Medicine at Johns Hopkins Medical School and the Bloomberg School of Public Health. Pat, I don't know about you, but Otis is a very impressive man, and he had a lot of really interesting things to say about his career development, family, et cetera in the first segment. This second segment, we're going to get to hear more about his time at the ACS. What were your thoughts about segment one? PATRICK LOEHRER: Well, I loved talking to Otis, and you too, Dave. Parenthetically, Otis once told me in a dinner conversation we had that he felt like Forrest Gump, and I can identify with that. Where over the field, our field of oncology over the last several decades, we've met some incredibly wonderful people, and we've been lucky to be part of the history. The three of us, I think, do have a deep sense of the historical context of oncology. This is a young field, and there's just some extraordinary people, many of them real true heroes, and Otis has his figure on the pulse of that. DAVID JOHNSON: Yeah, that's why he's been in some of the right places at the right time, and we'll hear more about that in this segment coming up now. PATRICK LOEHRER: Now Otis has had a career in many different areas, including ODAC, the NCI, the ACS, now at Hopkins. So let's hear a little bit more about Dr. Brawley's experience at the American Cancer Society and particularly with his experience with the former CEO, John Seffrin. DAVID JOHNSON: Sounds great. [MUSIC PLAYING] OTIS BRAWLEY: John and I had a wonderful run at the American Cancer Society. Got to do a lot of things. Got to testify for the Affordable Care Act. Got to do some of the science to actually argue that the Affordable Care Act would help. And I was fortunate enough to be there long enough to do some of the science to show that the Affordable Care Act is helping. DAVID JOHNSON: Yeah, I mean actually all of the things you accomplished at the ACS are truly amazing. Let me ask you, just on a personal level, what did you like most about that job, and then what did you like least about that job? [LAUGHTER] OTIS BRAWLEY: I like the fact-- there were a lot of things I liked about that job. There were a couple hundred scientists and scientific support people that you got to work with. And I used to always say, I do politics so you can do science. And what I used to like the most, every Wednesday afternoon that I was in town, I would walk around just to watch those people think. I used to joke around and say, I'm just walking around to see who came to work today. But I really enjoyed watching them work and watching them think, and that was fun. Another fun aspect of the job was people used to call and ask a little bit about the disease that they are a family member would have. And sitting down with them on the phone in those days-- we didn't have Zoom-- and talking to them through their disease. Not necessarily giving them advice on what to do in terms of treatment, but helping them understand the biology of the disease or connecting them with someone who was good in their disease. And I happen to, by the way, have sent some patients to both of you guys. That was a lot of fun. Then the other thing, of course, was the fact that you could actually influence policy and fix things. I'll never forget sitting across from Terry Branstad, then the governor of Iowa, and convincing him that the right thing to do is to raise the excise tax on tobacco in Iowa. Being able to see that you're effective and to see that you're positively influencing things. The bad side, some of the politics. I didn't necessarily like how some of the money was being raised or where they were raising money from. I think that you have to have a certain standard in terms of where you accept money. And we always had that tension with the fundraisers. But it's also true-- and I will give them a nod-- you can't do the fun things unless you raise money. So I really truly enjoyed my time at the American Cancer Society. And by the way, a shout out to Karen Knudsen, who is the CEO running the American Cancer Society now. And I'm fully committed to helping the ACS and helping Karen be successful. DAVID JOHNSON: One of the things I read-- I think I read this that you had said that one of your proudest accomplishments was revising the ACS screening guidelines. Tell us just a little bit about that. OTIS BRAWLEY: Yeah, going all the way back to the early 1990s, I started realizing that a lot of these guidelines for screening, or back then, this is before the NCCN guidelines for treatment even, that were published by various organizations, including the American Cancer Society. We're almost the equivalent of-- get the impression that in the 1960s, it would have been a smoke-filled room. But you gather a bunch of people into a room, and they come up with, this is what we should be doing. Indeed, the American Cancer Society in 1991 endorsed annual PSA screening for prostate cancer based purely on getting a group of primarily urologists into a room, and that's what they came up with. There was very little review of the science. There really was no science at that time except the science to show that PSA screening found cancer. There were no studies to show that led to men benefiting in that they didn't die. Indeed, in 1991, there was no study to show that treatment of early prostate cancer saved lives. The study to show treatment of prostate cancer saves lives was first published in 2003, and the radiation saves lives in 1997, 1998. Surgery saves lives in 2003 and screening has a small effect published in 2009. But they started recommending it in 1991 in this almost smoke-filled room kind of atmosphere. When I got to the American Cancer Society, I started an effort, and we involved people from the National Academy of Medicine, we involved people from the NCCN, from the American Urological Association, the American Academy of Family Physicians, the American College of Physicians. And we got together in that almost smoke-filled room again, but the idea was, how do you make responsible guidelines? And we wrote that up into a paper guide widely accepted by all of the organizations, and it involves a review of the literature that is commissioned by someone. And they spend a long time reviewing the literature and writing a literature review. And then you have a group of experts from various fields to include epidemiology and screening, social work, someone who's had the disease. Not just the surgeons and medical oncologists who treat the disease but some population scientists as well. They sit down and they reveal all of the scientific data, and then they start coming up with, we recommend this. And then they rank how strong that recommendation is based on the data. We published this in 2013 in The Journal of the American Medical Association. I do think that was important, you're right. That's Otis trying to bring his policy and his belief in orthodox approach to science and bring it all together. PATRICK LOEHRER: So let me reflect a little bit more on something. There is a book that I also just recently read by Dax-Devlon Ross, and it's a book entitled, Letters to my White Male Friends, and it was a fascinating read to me. You have this public persona and professional persona of being an outstanding physician, clinician, public speaker. But what we the three of us have never really had the conversation today is we have much more interest now in DEI. One of our other speakers talked about the fact that there's a tax that is placed upon underrepresented minorities and academics. They are all expected to be on committees. They have to be doing different things. And so the things that they love to do, they can't do it because they have to represent their race or their gender or their ethnicity. OTIS BRAWLEY: I have been blessed and fortunate. There are problems, and there are huge burdens that Black doctors, and women doctors by the way, have to carry. I have been fortunate that I have skated through without a lot of that burden. Maybe it has to do with oncology, but I will tell you that I have been helped by so many doctors, men and women, predominantly white, but some Asian, Muslim, Jewish, Christian. I don't know if it's oncology is selective of people who want to give folks a fair shake and really believe in mentoring and finding a protege and promoting their career. I have been incredibly, incredibly fortunate. Now that I say that, there are doctors, minority doctors and women, who don't have the benefits and don't have the fortunes that I have had, and we all have to be careful for that. As I said early on, John Altman told me that I will thank him by getting more Blacks and women into the old boys club. And so that was his realizing that there is a-- or there was a problem. I think there still is a problem in terms of diversity. Now I have seen personally some of the problem more outside of oncology in some of the other specialties. More in internal medicine and surgery, for example. By the way, there are also some benefit. I did well in medical school in third and fourth year in medical school at the University of Chicago because there were a group of Black nurses who were held that I wasn't going to fail. The nurses took me under their wing and taught me how to draw blood, how to pass a swan. The first code I ever called, there was a nurse standing behind me with the check off list. And so there are some advantages to being Black as well. But there are some disadvantages. I've been very fortunate. My advice to Black physicians is to keep an open mind and seek out the folks in medicine who truly do want to help you and truly do want to mentor you. And for the folks who are not minority or not women in medicine, I say, try to keep an open mind and try to help everybody equally. PATRICK LOEHRER: Thank you. DAVID JOHNSON: I want to go back to your book for a moment. And again, for those who've not read it, I would encourage them to do. So it's a really honest book, I think, well-written. You made a comment in there-- I want to make sure I quote it near correctly. You said that improvement in our health care system must be a bottom up process. What do you mean by "bottom up?" OTIS BRAWLEY: Well, much of it is driven by demand from patients and other folks. The name of the book was, How We Do Harm. And the synopsis is there are bunch of people who are harmed because they don't get the care that they need. And there's a bunch of people who are harmed because they get too much medicine and too much care. And they rob those resources away from the folks who don't get care at the same time that they're harmed by being overtreated, getting treatments that they don't need. The other thing, if I can add, in American health care, we don't stress risk reduction enough. I used to call it "prevention." Some of the survivors convince me to stress "activities to reduce risk of disease." We don't do a lot in this country in terms of diet and exercise. We try to do some work somewhat successfully on tobacco avoidance. We need to teach people how to be healthy. And if I were czar of medicine in the United States, I would try to make sure that everybody had a health coach. Many of us go to the gym and we have a trainer. We need trainers to teach us how to be healthy and how to do the right things to stay healthy. That's part of the bottom up. And in terms of costs you know my last paper that I published from the American Cancer Society, I published purposefully, this is my last paper. Ahmedin Jemal who's a wonderful epidemiologist who I happen to have worked with when I was at the National Cancer Institute and again later in my career at the American Cancer Society, I pushed Ahmedin-- he publishes these papers, and we estimate x number of people are going to be diagnosed with breast cancer and y number are going to die. He and I had talked for a long time about how college education reduces risk of cancer death dramatically. If you give a college education to a Black man, his risk of death from cancer goes down to less than the average risk for a white American. There's something about giving people college education that prevents cancer death. I simply challenged Ahmedin, calculate for me how many people in the United States would die if everybody had the risk of death of college-educated Americans. And he came back with of the 600,000 people who die in any given year, 132,000 would not die if they had all the things from prevention through screening, diagnosis, and treatment that college-educated people. Just think about that-- 132,000. Then I started trying to figure out what drug prevents 132,000 deaths per year? And I couldn't think of one until recently, and it happens to be the coronavirus vaccine. Which ironically has shown itself to be the greatest drug ever created in all of medicine. But in cancer, there's no breakthrough drug that is more effective than just simply getting every human being the care from risk reduction and prevention all the way through treatment that every human being ought to be getting. The solution to some of that starts with fixing third grade and teaching kids about exercise, about proper diet. PATRICK LOEHRER: We're going to have to wind things up here. But real quickly, a book you would recommend? OTIS BRAWLEY: Skip Trump, who's someone that we all know, wonderful guy used to run Roswell Park Cancer Center, just published a book actually it's coming out in September called, Centers of the Cancer Universe, A Half Century of Progress Against Cancer. I got a preprint of that, and it is a great book. It talks about what we've learned in oncology over the last 50 years since Richard Nixon signed the National Cancer Act. Keep in mind, he declared war on cancer on December 23, 1971. So we have an anniversary coming up in December. PATRICK LOEHRER: I want to close. Another book, I read the autobiography of Frederick Douglass. It's a wonderful read. It really is good. There were some endorsements at the end of this book, and one of them was written by a Benjamin Brawley, who wrote this review in a book called, The Negro in Literature and Art in 1921. And Benjamin Brawley was writing this about Frederick Douglass, but I would like to have you just reflect a moment. I think he was writing it about you, and I'm just going to read this. He basically said, at the time of his death in 1895, Douglass had won for himself a place of unique distinction. Large of heart and of mind, he was interested in every forward movement for his people, but his charity embraced all men in all races. His mutation was international, and today, many of his speeches are found to be the standard works of oratory. I think if your great, great grandfather were here today, he would be so incredibly proud of his protege, Otis. And it's such a privilege and pleasure to have you join us today on Oncology, Etc. Thank you so much. OTIS BRAWLEY: Thank you. And thank both of you for all the help you've given me over the years DAVID JOHNSON: Great pleasure having you today, Otis. I want to also thank all of our listeners for tuning in to Oncology, Etc. This is an ASCO educational podcast. We really are here to talk about anything and everything. So we're looking for ideas. Please, if you have any suggestions, feel free to email us at education@ASCO.org. Thanks again, and remember, Pat has a face for podcasts. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcasts. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

ASCO Daily News
Key Interventions and Patient Perspectives From #ASCOQLTY21

ASCO Daily News

Play Episode Listen Later Oct 5, 2021 23:01


Dr. Gabrielle Rocque, chair of the 2021 ASCO Quality Care Symposium, breast oncologist and health services researcher at the University of Alabama at Birmingham, and symposium chair-elect, Dr. Stephanie Wheeler, professor in the Department of Health Policy and Management at the University of North Carolina at Chapel Hill, discuss key interventions in quality care and compelling patient perspectives presented at #ASCOQLTY21. Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. On today's episode, we'll discuss promising interventions to improve the quality of care for patients and survivors and other key takeaways from the 2021 ASCO Quality Care Symposium. I'm delighted to welcome the chair and chair-elect of the [ASCO Quality Care] Symposium, Dr. Gabrielle Rocque and Dr. Stephanie Wheeler, for this discussion. Dr. Rocque is a breast oncologist and health services researcher. She is also associate professor of medicine in the Division of Hematology and Oncology and Gerontology, Geriatrics, and Palliative Care at the University of Alabama at Birmingham. Dr. Wheeler is a professor in the Department of Health Policy and Management at the University of North Carolina at Chapel Hill. She also serves as associate director of community outreach and engagement at the UNC Lineberger Comprehensive Cancer Center. My guests' full disclosures are available in our show notes, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Rocque and Dr. Wheeler, thanks for being on the podcast today. Dr. Gabrielle Rocque: Thank you for having us. ASCO Daily News: Dr. Wheeler, it was wonderful to have a hybrid event this year, with people participating in person in Boston and virtually. This is surely a sign of things to come. Can you tell us about some of the most important interventions in quality improvement that were presented at the [ASCO Quality Care] Symposium? Dr. Stephanie Wheeler: Absolutely, and thank you so much for hosting us. It was a really terrific [ASCO Quality Care] Symposium. And the fact that we had hybrid engagement from investigators all over the country and internationally was really exciting. There's a couple of intervention classes, if you want to call it that, that I think were particularly inspiring and interesting to me. The first were sets of interventions that focused on strategies to improve goals of care conversations and advanced care planning directives for patients with cancer or people with terminal illness in particular. And I just wanted to highlight a couple of those that I thought were particularly innovative. One was Abstract 8, which focused on using computer modeling and care coaches to increase advanced care planning conversations for people with advanced cancer. And this was presented by Dr. Divya Gupta. And it was just a wonderful example of how we can utilize technology and also care coaches. And in many cases, these don't necessarily have to be clinicians. They sometimes can be community health workers and others who can help direct those conversations and make it more comfortable for people living with advanced disease, and also their families, to consider next steps. In a similar vein, there were two other presentations--Abstract 1 delivered by Dr. Manali Patel and Abstract 2 delivered by Dr. Divya Parikh--that also utilized a similar model in a different care setting. And in those cases, the care settings ranged from VA to integrated health care settings. And we even had a conversation about how to do this work in community rural oncology practices. And I think that this kind of intervention has the potential for translation across a variety of settings. And the next steps are going to be figuring out exactly how to implement it in these settings. So, that's one class that I thought was particularly interesting. And I just want to highlight another group of interventions and studies that I found really innovative. And those were the presentations about hospital at-home models and how we can better deliver oncology care in the comfort of individuals' homes. And I thought Dr. Cardinale Smith did a great job from Mount Sinai describing the landscape of those interventions and the future for this kind of care delivery (“Overview of Programs and Ethics”). ASCO Daily News: Excellent. Great to hear about those promising new approaches. Dr. Rocque, the [ASCO Quality Care] Symposium captured many trends in quality care, including patient-reported outcomes measurement as an important way to monitor quality of care and patients' experiences. Can you highlight the studies that will help inform our listeners about how to integrate patient-reported outcomes into real-world settings? Dr. Gabrielle Rocque: Yeah. This was a major topic of the conference this year to think about how patient-reported outcomes are informative both in traditional research settings and in real-world settings. So, I was really intrigued by the Abstract 154 by Joy Jarnagin. And that abstract talked about how the changes in patient-reported outcomes actually had a very strong association with patients' treatment response, and in fact, was even more informative than those patients' tumor markers and I think show a novel way that patient-reported outcomes can be used. We also saw some more traditional abstracts on patient-reported outcomes. I'd like to highlight Abstract 152 by Valerie Lawhon, which really used patient-reported outcomes to identify patients' experience and their mental health outcomes during the COVID-19 pandemic, and I think provided us some really important insight into the experiences of our patients. And then as you mentioned, there is a lot of focus on real-world settings and how to transition from typical research patient-reported outcomes to a more broad scale implementation. And the session implementing PROs in oncology practice was really outstanding in terms of considering how this can be done. So, Dr. Terry Mulvey from Massachusetts General Hospital presented their experience on how to get these patient-reported outcomes into routine care, and what are some of the challenges associated with that, and how did they have to adapt to make sure that this was doable in real-world settings (“Challenges to Getting Started in a Practice Setting”). I was also impressed with the study by Dr. Raymond Osarogiagbon on the potential populations where there can be barriers of care and their study looking at an intervention in which they're implementing patient-reported outcomes over a wide variety of different practice types across the country (“Potential Populations Where This Can Be a Barrier to Care”). And I think these early insights also pointed us to future questions. Dr. Wynne Norton did a wonderful job of outlining some of the future questions that are likely to come up as we move into an era where patient-reported outcomes are a part of standard of care, and really think about how do we refine these for maximal benefit (“Overview of Current Strategies”). So, I think all of these sessions were highlighting the promise of patient-reported outcomes, as well as the future questions in this space. ASCO Daily News: Excellent. As a specialist in gerontology, geriatrics, and palliative care, please tell us about new approaches that oncologists should be aware of as they strive to provide high quality care for older patients and those receiving palliative care. Dr. Gabrielle Rocque: Absolutely. So, we've talked a bit about the patient-reported outcomes. And I think we'd be remiss in not highlighting the presentation on geriatric assessment--the presentations on the geriatric assessments into clinical practice by Dr. [Rawad] Elias (“Incorporating Geriatric Assessments Into Practice”). And I think this highlights another opportunity for us to move the field forward and take better care of our older adults. In terms of palliative care, there were multiple very informative abstracts. Dr. Wheeler has highlighted a few in the space of care guides or lay health coaches providing support in advanced care planning. In addition, we saw an interesting discussion of caregiver interventions for patients that are receiving--with cancer treatment by Dr. Nick Dionne-Odom (“Caregiver Interventions”). And I think it's important that we remember both the patients and the caregivers who are affected by cancer and by the amount of work that has to be done to support a patient with cancer going through their journey. ASCO Daily News: Absolutely, so important to remember caregivers and their needs and resources that could be available to them as well. Dr. Wheeler, financial toxicity is an enormous concern for many patients and their families, and the oncology care community has been trying for some time to figure out how best to address the concerns of patients and the health care system. Are there any new interventions that we should be aware of? Dr. Stephanie Wheeler: Yes, and I think that the [ASCO Quality Care] Symposium was an opportunity to hear about several of those. And some of them didn't make it onto the main stage but were featured in abstract sessions and poster sessions. So, as we're all well aware, financial toxicity is a multidimensional set of constructs that includes patients and their family's material out-of-pocket burden, as well as the psychological distress and potentially harmful care altering behaviors that financial hardship induces. And so, we continue to hear at the [ASCO Quality Care] Symposium multiple talks about the strain that patients are undergoing, including the non-medical hardship that's introduced by a cancer diagnosis. And that was really interesting, and I think important to document. But I think that where the field is moving is more towards interventions, both behavioral interventions and systems interventions, multilevel approaches to dealing with the hardship itself as well as the importance of policy. So, there were several abstracts that talked about the introduction of biosimilars and generics and how that affected price of many of the oncologic drugs available on the market. And frankly, the message is a bit discouraging. Prices continue to rise. And in some cases, the price increases are not limited to pharmacologic products. In some cases, we saw abstracts presenting the increased cost of surgery, of outpatient care appointments, and things like that as well. So, we're not going to fix the problem by managing drug pricing alone. In terms of patient and family-directed interventions, I thought that there were some interesting abstracts. I want to highlight a number 53--or excuse me, Abstract 43 by Melissa Beauchemin that focused on the existence of hospital specialty pharmacies and partnering with freestanding care coordination organizations to improve access to oncology medications, as well as Abstract 96 presented by Ms. Rachel Marquez which was focused on resolving transportation disparities and access to cancer treatments. These kinds of interventions are obviously patient directed but have tremendous potential. And then I also want to just note a couple of additional studies that are ongoing that are important to recognize in this field. There are at least five National Cancer Institute (NCI)-funded R01 trials underway right now investigating the role of financial navigation and various iterations of it in different care settings. So, I think we will want to look to this meeting as an opportunity to hear about that work as it moves forward. And how that work is implemented is going to be vital, because the types of care settings where it's being done--ranging from AYA populations in Utah, to urban populations in Washington state, to integrated care organizations in Northern California, all the way to parts of rural North Carolina--we're going to see a diversity of outcomes and different ways in which those types of interventions can manifest in those different studies. I also want to note that the NCI has funded a series of supplements through its Cancer Center Core Grant Initiative that are all focused on identification, timely identification of financial toxicity in practice. And many of the investigators leading that work were attending the [ASCO Quality Care] Symposium, and so that will be important to keep an eye on as we move forward as well. ASCO Daily News: Excellent. Dr. Rocque, let's focus on health equity and access. I'd like to ask you about the session on eliminating barriers to clinical trial access. The presenters of this session shared strategies to directly address inclusion and diversity in cancer care. Can you tell us about approaches that caught your attention? Dr. Gabrielle Rocque: Absolutely. So, this was a really great session talking about clinical trial access and barriers, and particularly as it relates to health equity. And so, in Abstract 74, Dr. Joe Unger presented a really interesting conceptual model that highlighted that the barriers to clinical trial access are not necessarily always at the patient level, but they are at the system level, the provider level. And this framework for considering how do we target in the future our ability to engage patients in clinical trials was really important, and I think was complemented well by the patient perspective from Rick Bangs, who's worked closely with SWOG, in thinking about how do patients view clinical trials and how can we better engage them. And I think folding together these different experiences and models to develop future interventions. I also thought the Abstract 75 looking at survival in the real-world analysis was noteworthy. And in particular, the ability to consider patients who are typically excluded from clinical trials based on their laboratory criteria and potentially having something like chronic kidney disease, and how little data there is on those patients who actually, in this study, had different outcomes after chemotherapy for breast cancer. I think when you think about clinical trial access and inclusion, I also think you need to think about how we collect our data and how we consider race and other social determinants of health. So, there were a few other abstracts that, although not in this session, I think were incredibly important for us to consider. The first is Abstract 78 by Ms. Niveditta Ramkumar that talked about the association between rurality and race and surgical treatment and outcomes for non-metastatic colon cancer. And so, she talked a bit about the intersectionality between race and rurality, and I think brings up an important topic that we need to think about these constructs, not only as individual constructs but how they impact each other as we consider analysis in the future. And also Abstract 80 by Dr. Kekoa Taparra, which was a really interesting abstract that talked about the disaggregation of Pacific Islanders in major Asian subpopulations to reveal hidden cancer disparities. So, in this abstract, he discussed how we often lump together different populations, potentially because of small numbers, who really may have very different experiences and characteristics. And I think challenges us to move the field forward by identifying populations in groups that are, in fact, very similar to each other and not just pulling this together. And I think that will have an impact on how we view engaging patients in clinical trials, as well as reporting those clinical trial results that allows our providers to understand how the trial results fit for the patient that is sitting in their clinic for whom they're making their decisions. ASCO Daily News: Indeed. Dr. Wheeler, is there anything that you'd like to add on the issue of access to clinical trials? Dr. Stephanie Wheeler: So, there was an abstract that particularly sparked my attention, [Abstract] 79 presented by Dr. Jenny Xiang about the VA Connecticut Cancer Experience, where universal pre-screening and using computer algorithms to identify patients who might be eligible for clinical trials was used. And I think that this is an important approach that can help us rely less on the assumptions and the biases that exist in clinical care practice about whether a patient may or may not participate in a clinical trial, and instead use the vast amounts of information that we know about them in their electronic health record to try to preemptively identify them and approach them. We know that when patients are asked and invited to be part of trials, they are much more likely to say yes than people assume. And this could be a more unbiased way of assessing that eligibility, and then proactively identifying people, ideally, with a trial navigator. I think that would enable us to potentially overcome some of the barriers that exist and that are, frankly, institutionally biased in many cases. ASCO Daily News: Thank you, Dr. Wheeler. Dr. Rocque, the [ASCO Quality Care] Symposium featured an excellent keynote address by Dr. Ben Corn of Hebrew University of Jerusalem (“Integrating Hope – Real Hope! – Into Clinical Oncology”) and a wonderful lecture by Dr. John Cox, who was honored with the Joseph V. Simone award for advancing quality cancer care (“Reshaping Practice: Necessary Trouble”). Can you share some highlights from their talks? Dr. Gabrielle Rocque: Definitely. So, the keynote address by Dr. Ben Corn was perfectly timed for this meeting. I think everyone has had a difficult past 2 years with the pandemic. And his message of the importance of hope really struck a chord with me and many of the attendees, and how this is something that we can strategically work to improve, and that hope is something we can modify and train for. And so, I'm really excited to both hear this lecture and then also see what's to come in the future in this domain of hope-related research. Another session that I would like to highlight as well is Dr. Cox's talk after receiving the Joe Simone Achievement Award. And his lecture highlighted that change is coming. And he emphasized the importance of changing payment structures to be able to improve the quality of care that patients receive and to be able to leverage those changes for infrastructure that allows us to enable our health system to have a more patient-centered approach with many of the types of interventions that we've been talking about here today. So, I think both of those sessions are really must-watch sessions that I would like to highlight today. ASCO Daily News: Excellent. Well, the [ASCO Quality Care] Symposium also heard some compelling patient perspectives. Dr. Wheeler, can you share some of these messages with us? Dr. Stephanie Wheeler: One of the most powerful sessions in the entire meeting was the very first one, which was focused on the metavivor experience (“The Patient Voice: “Metavivors” and Long-Term Survivorship Care”). And I think because part of the intention of the planning committee was to proactively feature patients' voices at this meeting, this particular session was almost entirely comprised of patients and survivors. And living with advanced disease, as we know now, is very different than it was in the past. And we know that patients living with incurable disease may sometimes go on to live 15, 20, 25 years. And their needs are quite different than patients who have early-stage cancer. And so, this session was impactful because it represented a range of experiences. We heard from a caregiver. We heard from a young woman who's living with stage four melanoma, Dr. Tarlise Townsend (“An AYA Perspective”). And one of the things that I took away from this session in particular was that our approaches in the way that we talk to metavivors has to be fundamentally different, that they want providers to be truthful, they want providers to acknowledge the uncertainty and prognosis and the sometimes complex and rapidly changing regimens that may be available for them in terms of dealing with their disease. But they don't want to be condescended to, they don't want to feel like there's information that is being withheld. One of the things that Dr. Townsend shared that was very powerful was that she talked about how her providers, in many cases, outlined an optimistic future for her and would give her maybe unfair expectations about what the future might hold and think about it in terms of the outlier effect. But that's not the case for many people with her condition. And so, she talked about having to do her own death work--and that's her term--and how much time she spent really trying to understand for herself what the future looked like. And it just resonated so much with me. And everybody on this panel had similar stories to share about their experiences. And it reminded me that at the end of the day, we're all human. None of us deal with uncertainty well. None of us deal with death well, or the prospect of death. But the best that we can do in these situations is to be open and honest and straightforward and recognize the fear and the hope and all of that being intermingled, and really respect the person's autonomy and the person's experience and their ability to make plans for themselves going forward. ASCO Daily News: Thank you, Dr. Wheeler. We will have links to these important patient perspectives in the transcript of this episode, as well as the other abstracts discussed today. Dr. Rocque and Dr. Wheeler, thank you very much for sharing these important highlights from the 2021 ASCO Quality Care Symposium. Dr. Stephanie Wheeler: Thank you for having us. Dr. Gabrielle Rocque: Thank you so much. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Gabrielle Rocque: Consulting or Advisory Role: Pfizer, Flatiron Research Funding: Carevive Systems, Genentech, Pfizer Travel, Accommodations, Expenses: Carevive (an immediate family member) Dr. Stephanie Wheeler: Research Funding (institution): Pfizer Foundation Travel, Accommodations, Expenses: Pfizer Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.