Podcasts about eortc

The OncoAlertWeekly Round Up   Covering the TOP of the week April 18-24, 2025  REGISTER at http://OncoAlert360.com OR https://oncoalert.m-pages.com/nhMpwe/oncoalert-newsletter-registration   Discussing:UPDATE on DESTINY-Breast09https://astrazeneca.com/media-centre/press-releases/2025/enhertu-combination-improved-pfs-in-1l-her-positive-mbc.htmlUPDATE on ASCENT 04https://gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-tripAnnual Report to the Nationon the Status of Cancer, featuring state-level statistics after the onset of the COVID-19 pandemichttps://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35833Osimertinib vs. Afatinib in 1L therapy of atypical EGFR-mutated metastatic non-small cell lung cancer https://lungcancerjournal.info/article/S0169-5002(25)00443-X/fulltextTargeting Lung Cancer with Precision: The ADC Therapeutic Revolutionhttps://link.springer.com/article/10.1007/s11912-025-01655-5Prevalence by therapy line and incidence of breast cancer brain metastases in 18 075 patientshttps://academic.oup.com/jnci/advance-article-abstract/doi/10.1093/jnci/djaf048/8101485?login=falseEuropean screening platform for EORTC clinical trials in advanced colorectal cancer ‘SPECTAcolor'https://esmogastro.org/article/S2949-8198(25)00037-8/fulltextKorea, Japan, Europe, and the United States: Why are guidelines for gastric cancer different?https://link.springer.com/article/10.1007/s10120-025-01613-xOutpatient Administration of Chimeric Antigen Receptor T-Cell Therapy Using Remote Patient Monitoringhttps://ascopubs.org/doi/10.1200/OP-25-00062Safety and Activity of Fibroblast Growth Factor Receptor Inhibitors in Advanced Malignancieshttps://ascopubs.org/doi/10.1200/PO-24-00896?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Dr. Chris Holsinger shares the new guideline from ASCO on transoral robotic surgery (TORS) for patients with oropharyngeal squamous cell carcinoma. He reviews the evidence-based recommendations on baseline assessment, the role of TORS in HPV-positive and HPV-negative disease and in the salvage/recurrent setting, which patients are eligible or ineligible for TORS, and the role of adjuvant therapy. He discusses the importance of multidisciplinary collaboration and shared decision-making between patients and their clinicians. Read the full guideline, “Transoral Robotic Surgery in the Multidisciplinary Care of Patients with Oropharyngeal Squamous Cell Carcinoma: ASCO Guideline.”   TRANSCRIPT This guideline, clinical tools, and resources are available at asco.org. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology.   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts, delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.    My name is Brittany Harvey and today I'm interviewing Dr. Chris Holsinger from Stanford University, lead author on “Transoral Robotic Surgery in the Multidisciplinary Care of Patients with Oropharyngeal Squamous Cell Carcinoma: ASCO Guideline.” Thank you for being here today, Dr. Holsinger. Dr. Chris Holsinger: Thanks, Brittany. We've been working together for years on these guidelines and what a pleasure to get to meet you at least virtually today. Brittany Harvey: Yes, it's great to have you on. And then just before we discuss this guideline, 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 disclosures of potential conflicts of interest for the guideline panel, including Dr. Holsinger, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So let's jump into this important guideline. Dr. Holsinger, to start us off, can you provide an overview of both the scope and purpose of this guideline? Dr. Chris Holsinger: Absolutely. And again, thanks for the opportunity to be here, Brittany. I appreciate the invitation to participate in the ASCO Guidelines and to work with the great people on this paper that's now out there. I think it's a really important guideline to be published because it really talks about surgery, specifically transoral robotic surgery, a minimally invasive technique, as a new way to treat head and neck cancer. Why that's so important is that what is now known as head and neck cancer is completely different than what we saw even 25 years ago. Around the turn of the century, some really thoughtful epidemiologists working at Hopkins and UW in Seattle started to see this connection between the human papillomavirus and head and neck cancer. And since then we've seen this precipitous rise in the number of throat cancers specifically due to HPV. The results from the American Cancer Society showed last year that head neck cancer, in particular these cancers of the oropharynx, actually were one of the few cancers that still had an increasing incidence, I think it was around 2.5% per year. And other studies have shown that almost 50% of the cases we're seeing across the United States now are actually HPV-mediated throat cancers. That's bad news because we're seeing this rise in cases, but it's good news in the sense that this is a cancer that is highly curable and I think opens up a lot of different treatment avenues that we didn't have a couple of decades ago. And when patients are facing a mortality risk that's two or three times lower than the formerly HPV-negative smoking-driven cancers, it really behooves us as clinicians, as oncologists to think about treatment selection in a completely different way. And for years, the only function-sparing option, surgery certainly was not, was radiation therapy with concurrent cisplatin chemotherapy. In 2009, the FDA approved the use of surgical robotics using a transoral approach, a minimally invasive approach to resect the primary tumors and to perform neck dissection. And so now when patients walk in the door, they not only have this gold standard option in the path of radiation therapy with chemo, but also frontline surgery. And with some recent publications, especially the ECOG 3311 study, there's some really good evidence that for HPV-mediated throat cancers, we can actually de-escalate the intensity of adjuvant therapy when we start with surgery first. So who we choose that option for, which patients want that option - these are all really important new questions that we try to grapple with in these guidelines. Brittany Harvey: That background is really key for setting the stage for what we're about to talk about today. And so next I'd like to review the key recommendations across the clinical questions that the panel addressed. So you just talked about the importance of treatment selection. So to start that off, first, what is recommended for baseline assessment for patients with oropharyngeal squamous cell carcinoma who are being considered for transoral robotic surgery? Dr. Chris Holsinger: So I think here we tried in the guidelines to really standardize the workup and approach of this disease, in general, but with a strong focus on who might be a good surgical candidate. As I mentioned in the introduction, I mean, this is a disease that is very new. Our workup is in flux. And so what we tried to do, especially in items 1.2 and 1.3, is to really standardize and confirm that the tumor that we're dealing with, which oftentimes presents in a metastatic lymph node, is in fact associated with the human papillomavirus. So how biopsy is done, how high risk HPV testing is performed, whether you're doing that with an in situ hybridization, a DNA based study, or a p16 immunohistochemical study. And we try to tackle these issues first to really make sure that the patient population we're considering is actually indeed eligible for this kind of treatment de-escalation with surgery. Brittany Harvey: Understood. So it's important to consider which patients could be eligible for TORS upfront. So what is the role of TORS in patients with HPV-positive oropharyngeal squamous cell carcinoma? Dr. Chris Holsinger: Yeah, exactly. So I think first of all, surgery is ideally suited, and the robot is FDA approved for early-stage cancers - T1 and T2 cancers that are amenable to a minimally invasive approach. And we really try to emphasize, especially in our patient selection section of the guideline, who is really an ideal candidate for this. It's not just the T1 and T2 tumor. It's a tumor that is lateralized so that we can maybe consider managing the neck concurrently just on the side of the tumor, rather than doing bilateral neck dissection for most patients. Which patients might get the best functional outcome is a really critical component of this. And in fact, that actually goes back to a guideline that we didn't have time to chat about earlier, which is that we think every head neck cancer patient, whether or not they're being considered for transoral robotic surgery or frontline radiation therapy with cisplatin, every patient should have a pre-treatment assessment by a speech and swallowing expert. They're called different names across the country: speech language pathologists, speech pathologists, etc. But having a really good functional assessment of the patient's ability to swallow before treatment selection is really critical. And why that's important with frontline surgery is that there's a period of about one or two weeks after which that patient really needs intensive rehabilitation. And so for every patient being considered by TORS, we want to work really hand in hand with that speech pathologist to do pre-habilitation and then immediate post-operative rehab and then long longitudinal rehabilitation so that if radiation is needed down the road in a month, that patient just hopefully sails through this de-escalated treatment that we're offering. Brittany Harvey: Great. I appreciate you describing which patients can be considered for transoral robotic surgery. So beyond that, which patients with HPV-positive oropharyngeal squamous cell carcinoma aren't really good candidates for TORS? Dr. Chris Holsinger: We talked about that sort of ideal patient, but you know, we're not always living in an ideal world. And so I think it's important, and I'm really happy about the multidisciplinary discussions that led to these final guidelines because I think it helped engage radiation oncologists, medical oncologists, and surgeons around who's maybe not a good candidate for this because radiation therapy, with or without cisplatin chemotherapy, remains a good option for many of these patients. But I think the consensus, especially among the surgeons in this group, were that patients with tumors were more endophytic - that's the old fashioned oncology and surgical oncology term that refers to tumors that seem to not be as evident on the surface and have more of an infiltrative deep growth pattern - these are not ideal tumors. Whereas an exophytic tumor that's growing upwards, that's more readily seen on flexible endoscopy during a routine clinic assessment, or frankly, better seen on imaging, those exophytic tumors are better suited to a surgical approach because the surgeon has a better chance when he or she sees the tumor to get a good margin. When we can appreciate not just the surface mucosal margins that need to be taken, but also have a better chance to appreciate their depth. And with those infiltrative tumors, it's much harder to really understand how to get that deep margin, which in many cases is always the hardest. And so that's a long way to say that surgical decision making, patient selection is really critical when it comes to offering TORS as a multidisciplinary group. And then there are a few other things that we can quickly talk about before we move on to discussing adjuvant therapy. But I think there are some relative contraindications to patients who might have tumors arising in a palatine tonsil or tonsillar pillar, but which might grow significantly into the soft palate, such that a major palatal resection would be needed to get a good margin. For T1 and T2 tumors, we're not sure that that is an ideal candidate. And the other relative contraindication, but it's a hard and fast contraindication in my personal practice, is patients with extensive nodal disease. I think a patient who has preoperative extranodal extension, matted nodes, clinically and on MRI, you know pre-op they're going to need intensive post operative concurrent chemoradiation post-op that's maybe not the best patient for TORS, although there are some select cases where that that might make sense. But that's a quick overview of patient selection for TORS, Brittany. Hopefully, that's helpful. Brittany Harvey: That's definitely helpful. I think it's really important to consider not only who is eligible, but who isn't eligible for this de-escalation of treatment, and I appreciate you clarifying some of that. So then you've just also mentioned adjuvant therapy along with multidisciplinary discussion. So what is recommended regarding adjuvant therapy for patients who have resected HPV-positive oropharyngeal squamous cell carcinoma? Dr. Chris Holsinger: Definitely. And I think the post-operative discussion has to begin with great pre-op planning. And pre-op planning is really anchored in a really robust multidisciplinary team. So, we spoke earlier about the critical importance of getting speech language pathology involved initially, but they're part of a much larger team that includes not just a surgeon, but medical oncologist, a radiation oncologist and a dental oncologist - all of these specialties, and I could think of several others if we had time to chat further - this should also be really engaged in the care of these patients. But great decision making regarding adjuvant therapy really begins with a robust multidisciplinary consultation pre-op and we try to emphasize that in the guidelines. But just to return and answer your question very directly, I think adjuvant therapy is really the critical piece in getting that great functional outcome for a patient with HPV-mediated throat cancer. And I think traditionally patients who have a variety of different risks, based on a large study done again by the ECOG group, ECOG 3311, we showed that by stratifying patients based on their surgical pathology rather than on an estimate of disease extent, we can better stratify adjuvant therapy. And so the low risk patient is a patient with good margins and of course, good margin, we could spend another two hours discussing that. But good margins are greater than at least 1 to 3 millimeters superficially and a clear deep margin. Patients with lymph node metastases that are less than 3 cm and a single lymph node can sometimes be observed but most patients don't fall into that low risk category. Most patients fall into an intermediate risk where the margin is good and it's clear, but it might be close. That depends if you're talking about the superficial mucosal margin or the deep. But more often than not, we spend a lot of time considering the extent of lymph node involvement as it pertains to how adjuvant therapy is delivered. And I think for patients with less than 4 lymph nodes traditionally without extranodal extension, radiation therapy will suffice for adjuvant therapy after TORS. And the question of dose then comes up. Are we talking 50 Gray, the experimental arm that showed real promise in the ECOG 3311 trial, or 60 Gray or more traditional dose? And that is a topic definitely for another podcast, which we should do with a radiation oncologist online. I don't want to get into the weeds with that, but I refer you to our guidelines and Bob Ferris and Barbara Burtness' paper from JCO in 2021 for further details about that. But then for patients with positive margins with more than four lymph nodes, but especially patients with extranodal extension, the role of radiation therapy and chemotherapy is really absolutely critical. Because these patients and while they only accounted for around 20% to 30% of patients that we're seeing in this new era of TORS, they're the ones that we're really focusing on how can we do better because their overall survival is still good, it's 90%, but it's not as good as the patients we're seeing with a low and intermediate risk. So that's a brief overview there. Brittany Harvey: I appreciate that overview. And yes, we'll refer listeners to the full guideline, which is linked in the show notes of this episode to learn more about the intricacies of the radiation therapy that you mentioned. So then we've talked a lot about patients with HPV-positive disease, but what is the role of TORS in patients with HPV-negative disease? Dr. Chris Holsinger: I think TORS still has a role for these patients. Our colleague in India, Surender Dabas, has a really nice series that shows that for HPV-negative patients, this is a way for early stage cancers to potentially escalate the intensity of treatment for a disease that does worse than this new HPV-positive we're seeing in the US. So I think there's a good signal there. I think more study needs to be done and I think those studies, in fact, are underway in India and other countries. I hope that we can, as an oncology community here in the United States, also tackle this disease, which is still a significant part of the disease we face in head and neck oncology. Brittany Harvey: Yes, we'll look forward to more data coming out for HPV-negative disease. So then, the last clinical question that the guideline panel addressed: What is the role of TORS in the salvage or recurrent setting? Dr. Chris Holsinger: So we wrap up the guidelines tackling this topic. It's definitely something for the experienced TORS surgeon in consultation with that multidisciplinary team. Oftentimes, we are still seeing many patients who need salvage surgery and I think, while TORS alone could be a really effective treatment option, TORS with a microvascular reconstruction is oftentimes what is needed for these patients who, with recurrence, do often present with an RT 2, 3, 4 tumor. In my own practice, I found that using TORS as a way to minimize the superficial mucosal extent and then delivering that tumor through a traditional lateral pharyngotomy, then neck dissection and then having a microvascular flap inset done after that really provides the best possible chance for good long term function and of course control of the tumor. Here, I definitely refer the listener to some great work done out of the Royal Marsden with Vin Paleri, who we're happy to have on our TORS guideline panel for his RECUT study that really grapples in some detail with these very issues. Brittany Harvey: Excellent. And so we've covered a lot of the recommendations here that were made by the panel and you've touched a little bit about how this changes things for clinicians in practice. But what should clinicians know as they implement these new recommendations? Dr. Chris Holsinger: One thing as we close, I hope that in the future we can really start to grapple with this concept of patient selection. I think these guidelines help establish that TORS is a great oncologic option with - really the only option for treatment de-escalation in the here and now. Radiation therapy and cisplatin concurrent chemotherapy is going to be an option that is such an important choice for patients. And I think where I hope the field goes in the future is figuring out which patient wants one of these options. And I think certain patients really want that tumor taken out and others just the idea of surgery is not something that makes sense for them. How we in the context of a multidisciplinary team, really engage that patient, elicit their treatment preferences and then through considering treatment eligibility criteria that we've spelled out here for surgery and can be spelled out for chemo RT, bringing all that together in a formal shared decision making process is really where I hope the field will be going in the next few years. And hopefully these guidelines help to pave the way there. Brittany Harvey: Definitely the aspect of care by a multidisciplinary team and talking with patients to go through shared decision making is key to implementing these guidelines. So then, in that same vein, what do these recommendations mean for patients with oropharyngeal squamous cell carcinoma? Dr. Chris Holsinger: I think the central take home message for patients should be that especially if you have a T1 and T2 tumor, it's really important to have that consultation with a surgeon who knows how to do TORS and has a busy practice, but then also having an honest discussion up front about what the functional outcomes would be both with surgery and also chemo RT. And I think just knowing all those different options, that multidisciplinary treatment selection process is going to be that much more robust. And I think more right decisions will get made and we'll see less decisional regret down the road, which I think is a long term goal of our field. Brittany Harvey: Absolutely. That discussion of preferences is key. So then to wrap us up, you touched on this a little bit earlier in talking about ongoing research and data, particularly in the field of HPV-negative disease, but what are the outstanding questions regarding TORS in this patient population? Dr. Chris Holsinger: Yeah, I think that in addition to this work around shared decision making, I really hope that we'll embrace shared decision making in the context of future clinical trial. I think where we are now is you have surgeons saying, “Hey, TORS and 50 gray is a great option. Why aren't we doing that?” And then our colleagues, perhaps across the aisle, if I can use a political metaphor, are saying, “Well, where's the comparative data? Can we even do a randomized clinical trial between surgery and radiation?” Well, Christian Simon in Lausanne in Switzerland is trying to do this in a small pilot study being led by the EORTC, and I would encourage American investigators to consider something analogous. But I think how we solve this question of I think treatment choice is going to be pivotal for any such trial to ever be done. And then finally, I think, how will the changing treatment landscape around immunotherapy change this? There's some really provocative data that dates back to 1996 in a JCO paper from Ollivier Laccourreye and the University of Paris experience that showed induction chemotherapy followed by function preserving surgery in the larynx was a really powerful strategy for organ preservation, and that has never been followed up in the United States. And so especially with the upcoming presentation of KEYNOTE-689, will we be doing neoadjuvant approaches for patients and then following them by minimally invasive surgery or lower dose radiation? I think these are going to be some exciting new areas of study and I can't wait to see how this might evolve so we can refine the treatment - still get those great outcomes, but reduce those late toxicity. Brittany Harvey: Yes. We'll look forward to this ongoing research to continue to move the field forward. So, Dr. Holsinger, I want to thank you so much for your time to develop this important guideline. It's been great to have you on the podcast to discuss it today. Dr. Chris Holsinger: Well, thanks a lot Brittany. It's nice to finally meet you. Brittany Harvey: Likewise. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/head-neck-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store 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.   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. Guest 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.

Featuring an interview with Dr Seth Wander, including the following topics: The clinical utility of ESR1 mutations in HR-positive, HER2-negative advanced breast cancer Grinshpun A et al. The clinical utility of ESR1 mutations in hormone receptor-positive, HER2-negative advanced breast cancer. Hematol Oncol Clin North Am 2023;37(1):169-81. Abstract (0:00) Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy for ER-positive, HER2-negative advanced breast cancer Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Phase Ia/Ib EMBER study. J Clin Oncol 2024;[Online ahead of print]. Abstract (6:01) EORTC-2129-BCG: Elacestrant for ER-positive/HER2-negative breast cancer patients with ctDNA relapse Ignatiadis M et al. EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA). ESMO 2024;Abstract 338TiP. (8:20) CME information and select publications  

El Dr. Jerónimo Rodríguez Cid, oncólogo médico de la Ciudad de México, presenta un resumen de los estudios que consideran más relevantes en el ámbito del melanoma expuestos durante el Congreso de ESMO 2024. EORTC-1208 KEYMAKER-U02 02C Abstract LBA41 CheckMate 76K KEYNOTE-716 NADINA CheckMate 067 KEYNOTE-006 Fecha de grabación: 24 de septiembre de 2024.                       Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Professor Gemma Kenter to discuss EORTC 55994. Prof. Kener is emeritus professor in gynae-oncology and was head of the department gynae-oncology in Center of Gynaecological Oncology Amsterdam (Amsterdam University Medical Center and Dutch Cancer Center). Her scientific interest concerns treatment and translational research of carcinoma of the cervix.     Highlights: In Trial EORTC 55994 we found no difference in overall survival between neoadjuvant chemotherapy followed by radical surgery and concomitant chemoradiation in case of bulky cervical cancer.  Regions in the world with a high incidence of cancer of the cervix might have poor access to radiotherapy. For patients in these centers as well as for young women who want to perceive their ovarian function, neoadjuvant chemotherapy followed by radical surgery can be a good alternative.

Edward Gibbon, an English historian and politician, once quipped, "History is indeed little more than the register of the crimes, follies, and misfortunes of mankind." This episode, which lacks historians and politicians, covers testicular cancer, a topic humankind has had a love-hate relationship with for millennia. As a historical concept in the middle ages, men who wanted to have a male as an offspring would sometimes remove their left testicles as the belief was that "boy" sperm was made in the right testicle and "girl" sperm in the left. We don't entertain such nonsense here on Oncology for the Inquisitive Mind. Instead, we discuss testicular cancer, an uplifting episode with high cure rates and a debate regarding observation versus treatment. Will there be a future when one can perform surgery alone? Does radiotherapy have a role, and do the pros outweigh the cons of chemotherapy?Links to studies discussed in this episode (subscription may be required):EORTC 30982 study: https://pubmed.ncbi.nlm.nih.gov/21282539/Comparison of Two Standard Chemotherapy Regimens for Good-Prognosis Germ Cell Tumors: Updated Analysis of a Randomized Trial: https://academic.oup.com/jnci/article/102/16/1253/2568956For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Drs Sandhya Srinivas and Rana R. McKay discuss bone health and survivorship, including risk factors and potential side effects with androgen deprivation therapy in patients with prostate cancer. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988732). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Metastases in Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/29661810/ Do Dietary Calcium and Vitamin D Matter in Men With Prostate Cancer? https://pubmed.ncbi.nlm.nih.gov/29765146/ Zoledronic Acid: A Review of Its Use in the Management of Bone Metastases and Hypercalcaemia of Malignancy https://pubmed.ncbi.nlm.nih.gov/12558465/ Denosumab in Osteoporosis https://pubmed.ncbi.nlm.nih.gov/24289327/ Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/23863050/ Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/28030702/ The Prevention of Fragility Fractures in Patients With Non-Metastatic Prostate Cancer: A Position Statement by the International Osteoporosis Foundation https://pubmed.ncbi.nlm.nih.gov/29088899/ Decreased Fracture Rate by Mandating Bone Protecting Agents in the EORTC 1333/PEACEIII Trial Combining Ra223 With Enzalutamide Versus Enzalutamide Alone: An Updated Safety Analysis. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.5002 Addition of Radium-223 to Abiraterone Acetate and Prednisone or Prednisolone in Patients With Castration-Resistant Prostate Cancer and Bone Metastases (ERA 223): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/30738780/

Check out the latest QuadCast episode as we highlight the benefit of PET scans in breast cancer staging, patterns of recurrence from the EORTC 22922 trial, the safety of radiation with brentuximab vedotin, the expanding role of SRS for non-malignant indications, and an interesting fact of lung cancer screening. quadshotnews@gmail.comwww.quadshotnews.com

In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. The first scenario involves a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease.  Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:12), review research evidence regarding systemic and radiation therapy for high-risk localized disease (5:45), and reflect on the importance of genetic testing and (10:57) and considerations for treatment approaches at progression to metastatic disease (16:13).  Speaker Disclosures Dr. Kriti Mittal:  Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health  Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group  Research Funding - Pfizer Dr. Jorge Garcia:  Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology;  Genentech/Roche; Lilly  Other Relationship - FDA Resources  ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today we'll explore how we interpret and integrate recently reported clinical research into practice, focusing on two clinical scenarios: localized prostate cancer progressing to hormone-sensitive metastatic disease; and a case of de novo metastatic hormone-sensitive prostate cancer progressing to castration-resistant disease.   My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist chair and the current chair of the Solid Tumor Oncology Division at University Hospital's Seidman Cancer Center. Let me begin by presenting the first patient scenario.  Case 1: A 72-year-old male was referred to urology for evaluation of hematuria. A rectal exam revealed an enlarged prostate without any nodules. A CT urogram was performed that revealed an enlarged prostate with bladder trabeculations. A cystoscopy revealed no stones or tumors in the bladder, but the prostatic urethra appeared to be abnormal looking. Transurethral resection of the prostate was performed. The pathology revealed Gleason score 4+5=9 prostate cancer, involving 90% of the submitted tissue. PSA was performed one week later and was elevated at 50. Patient declined the option of radical prostatectomy and was referred to radiation and medical oncology.   So I guess the question at this point is, Dr. Garcia, in 2023, how do you stage patients with high-risk localized prostate cancer and how would you approach this case? Dr. Jorge Garcia: That's a great question and a great case, by the way, sort of what you and I in our practice will call ‘bread and butter'. Patients like this type of case that you just presented come from different places to our practice.  So either they come through urology or oftentimes they may come through radiation oncology. And certainly, it depends where you practice in the United States, at ‘X', US, they may come through medical oncology.   So I think that the first question that I have is in whatever role I'm playing in this case, where the patient has seen a urologist or a rad onc or me first, I think it's important for us in medical oncology, at least in the prostate cancer space, to talk about how do we think of their case and put those comments into context for the patient. It's very simple for you to tell a patient you can probably have surgery, radiation therapy, but at the end of the day, how do you counsel that patient as to the implications of the features of his disease is going to be really important. I use very simple examples that I relate to my patients, but really this patient is a patient that has very high-risk prostate cancer based upon the NCCN guidelines and how we actually stratify patients into what we call low-risk, intermediate-, and high-risk, and between those very low and very high risk.  So his PSA is high, very high, I would argue. His Gleason score, now, what we call group grading is high. He has high-volume disease. So the first question that I would have is, what are the choices for treatment for a patient like this? But even before you and I may talk about treatment options, we really want to understand the volume of their disease and whether or not they have localized prostate cancer with high-risk features or whether or not they have locally advanced or hopefully not metastatic disease. So back in the days prior to the FDA approval for PSMA PET imaging, we probably will have a Technetium-99 whole-body bone scan, and/or we probably will actually use CT scanning. Most people in the past, we used to do just a CT of the abdomen and pelvic region. As you know, with the movement of oral agents in the advanced setting, I think most of us will do a chest CT, abdomen and pelvic region, and certainly we also probably will have a Technetium-99 bone scan.  Now, with the utility and the use of PET imaging, I think most people like him will probably undergo PET PSMA, where you use F-18 PSMA or Gallium-68 PSMA. I think the importance depends on how you look at the approval of these two technologies. I think that PET PSMA imaging is here to stay. It's probably what most of us will use. And based upon that, we will define yet the truest stage of this patient. So right now, what we know is he has high-risk features. Hopefully, their disease is localized. We'll probably put the patient through an imaging technology. If you don't have access to a PET, then obviously CT and a bone scan will do. But if you do, the PET will actually help us define if the patient has disease outside of the prostate region, in the pelvic area, or even if they have distant metastases. Dr. Kriti Mittal: I would agree with that approach, Dr. Garcia. I think in the United States, we've been late adopters of PSMA scans. I think this patient with high-risk localized disease, if insurance allows at our institution, would get a PSMA for staging. There are still some patients where insurance companies, despite peer-to-peer evaluations, are not approving PSMAs. And in those situations, the patient would benefit from conventional CTs and a bone scan. So let's say this patient had a PSMA and was found not to have any regional or distant metastases. He decided against surgery, and he is seeing you as his medical oncologist together with radiation. What would your recommendations be?  Dr. Jorge Garcia: I think the bigger question is, do we have any data to suggest or to demonstrate that if in the absence of metastatic disease with conventional imaging or with emerging technologies such as PSMA PET, there is no evidence of distant disease, which I think you probably agree with me, that would be sort of unlikely with a patient with these features not to have some form of PSMA uptake somewhere in their body. But let's assume that indeed then the PSMA PET was negative, so we're really talking about high-risk localized prostate cancer. So I don't think we can tell a patient that radical prostatectomy would not be a standard of care. We never had a randomized trial comparing surgery against radiation therapy. This patient has already made that decision and surgery is not an option for him. If he, indeed, had elected radiotherapy, the three bigger questions that I ask myself are where are you going to aim the beam of that radiation therapy? What technology, dose, and fractionation are you going to use? And lastly, what sort of systemic therapy do you need, if any, for that matter? Where we do have some data maybe less controversial today in 2023 compared to the past? But I think the question is, do we do radiation to the prostate only or do we expand the field of that radiation to include the pelvic nodes?  Secondly, do we use IMRT? Do you use proton beam or not? Again, that's a big question that I think that opens up significant discussions. But more important, in my opinion, is the term of hypofractionation. I think the field of radiation oncology has shifted away from the old standard, five, seven weeks of radiation therapy to more hypofractionation, which in simple terms means a higher dose over a short period of time. And there was a concern in the past that when you give more radiation on a short period of time, toxicities or side effects would increase. And I think that there is plenty of data right now, very elegant data, demonstrated that hypofractionation is not worse with regards to side effects. I think most of us will be doing or supporting hypofractionation. And perhaps even to stretch that, the question now is of SBRT. Can we offer SBRT to a selected group of patients with high-risk prostate cancer? And again, those are discussions that we will naturally, I assume, in your practice, in your group, you probably also have along with radiation oncology.  Now, the bigger question, which in my mind is really not debatable today in the United States, is the need for systemic therapy. And I think we all will go back to the old data from the European EORTC data looking at the duration of androgen deprivation therapy. And I think most of us would suggest that at the very least, 24 months of androgen deprivation therapy is the standard of care for men with high-risk prostate cancer who elect to have local definitive radiation therapy as their modality of treatment. I think that whether or not it's 24 or 36, I think that the Canadian data looking at 18 months didn't hit the mark. But I think the radiation oncology community in the prostate cancer space probably has agreed that 24 months clinically is the right sort of the sweetest spot.  What I think is a bit different right now is whether or not these patients need treatment intensification. And we have now very elegant data from the British group and also from the French group, suggesting, in fact, that patients with very high-risk prostate cancer who don't have evidence of objective metastasis may, in fact, benefit from ADT plus one of the novel hormonal agents, in this case, the use of an adrenal biosynthesis inhibitor such as abiraterone acetate. So I think in my practice, what I would counsel this patient is to probably embark on radiotherapy as local definitive therapy and also to consider 24 months of androgen deprivation therapy. But I would, based upon his Gleason score of group grading, his high-volume disease in the prostate gland, and his PSA, to probably consider the use of the addition of abiraterone in that context. Dr. Kriti Mittal: That is in fact how this patient was offered treatment. The patient decided to proceed with radiation therapy with two years of androgen deprivation. And based on data from the multi-arm STAMPEDE platform, the patient met two of the following three high-risk features Gleason score >8, PSA >40, and clinical >T3 disease. He was offered two years of abiraterone therapy. Unfortunately, the patient chose to decline upfront intensification of therapy. In addition, given the diagnosis of high-risk localized prostate cancer, the patient was also referred to genetic counseling based on the current Philadelphia Consensus Conference guidelines. Germline testing should be considered in patients with high-risk localized node-positive or metastatic prostate cancer, regardless of their family history. In addition, patients with intermediate-risk prostate cancer who have cribriform histology should also consider germline genetic testing.  Access to genetic counseling remains a challenge at several sites across the US, including ours. There is a growing need to educate urologists and medical oncologists to make them feel comfortable administering pretest counseling themselves and potentially ordering the test while waiting for the results and then referring patients who are found to have abnormalities for a formal genetics evaluation. In fact, the Philadelphia Consensus Conference Guideline offers a very elegant framework to help implement this workflow paradigm in clinical practice. And at our site, one of our fellows is actually using this as a research project so that patients don't have to wait months to be seen by genetics. This will have implications, as we will see later in this podcast, not only for this individual patient as we talk about the role of PARP inhibitors but also has implications for cascade testing and preventative cancer screening in the next of kin. Dr. Jorge Garcia: Dr. Mittal, I think that we cannot stress enough the importance of genetic testing for these patients. Oftentimes I think one of the challenges that our patients are facing is how they come into the system. If you come through urology, especially in the community side, what I have heard is that there are challenges trying to get to that genetic counsel. Not so much because you cannot do the test, but rather the interpretation of the testing and the downstream effect as you're describing the consequences of having a positive test and how you're going to counsel that patient. If you disregard the potential of you having an active agent based upon your genomic alteration, is the downstream of how your family may be impacted by a finding such as the DNA repair deficiency or something of that nature. So for us at major academic institutions because the flow how those patients come through us, and certainly the bigger utilization of multi-disciplinary clinics where we actually have more proximity with radiation oncology urology, and we actually maybe finesse those cases through the three teams more often than not, at least discuss them, then I think that's less likely to occur. But I think the bigger question is the timing of when we do testing and how we do it.  So there are two ways -- and I'd love to hear how you do it at your institution -- because there are two ways that I can think one can do that. The low-hanging fruit is you have tissue material from the biopsy specimen. So what you do, you actually use any of the commercial platforms to do genomic or next-generation sequencing or you can do in-house sequencing if your facility has an in-house lab that can do testing. And that only gets you to what we call ‘somatic testing', which is really epigenetic changes over time that are only found in abnormal cells. It may not tell you the entire story of that patient because you may be missing the potential of identifying a germline finding. So when you do that, did you do germline testing at the same time that you do somatic testing or did you start with one and then you send to genetic counseling and then they define who gets germline testing? Dr. Kriti Mittal: So at our site, we start with germline genetic testing. We use either blood testing or a cheek swab assay and we send the full 84-gene multigene panel. Dr. Jorge Garcia: Yeah, and I think for our audience, Dr. Mittal, that's great. I don't think you and I will be too draconian deciding which platform one uses. It's just that we want to make sure that at least you test those patients. And I think the importance of this is if you look at the New England Journal paper from many years ago, from the Pritchard data looking at the incidence of DNA repair deficiency in men with prostate cancer in North America, that was about what,  around 10% or so, take it or leave it. So if you were to look only for germline testing, you only will, in theory, capture around 10% of patients. But if you add somatic changes that are also impacting the DNA pathway, then you may add around 23%, 25% of patients. So we really are talking that if we only do one type of testing, we may be missing a significant proportion of patients who still may be candidates, maybe not for family counseling if you had a somatic change, rather than germline testing, the positivity, but if you do have somatic, then you can add into that equation the potential for that patient to embark on PARP inhibitors down the road as you stated earlier. It may not change how we think of the patient today, or the treatment for that matter. But you may allow to counsel that patient differently and may allow to sequence your treatments in a different way based upon the findings that you have. So I could not stress the importance of the NCCN guidelines and the importance of doing genetic testing for pretty much the vast majority of our patients with prostate cancer. Dr. Kriti Mittal: Going back to our patient, three years after completion of his therapy, the patient was noted to have a rising PSA. On surveillance testing, his PSA rose from 0.05 a few months prior to 12.2 at the time of his medical oncology appointment. He was also noted to have worsening low back pain. A PSMA scan was performed that was noteworthy for innumerable intensely PSMA avid osseous lesions throughout his axial and appendicular skeleton. The largest lesion involved the right acetabulum and the right ischium. Multiple additional sizable lesions were seen throughout the pelvis and spine without any evidence of pathologic fractures. So the question is, what do we do next? Dr. Jorge Garcia: The first question that I would have is, the patient completed ADT, right? So the patient did not have treatment intensification, but at the very least he got at least systemic therapy based upon the EORTC data. And therefore, one would predict that his outcome will have been improved compared to those patients who receive either no ADT or less time on ADT. But what I'm interested in understanding is his nadir PSA matters to me while he was on radiation and ADT. I would like to know if his nadir PSA was undetectable, that's one thing. If he was unable to achieve an undetectable PSA nadir, that would be a different thought process for me.   And secondly, before I can comment, I would like to know if you have access to his testosterone level. Because notably, what happens to patients like this maybe is that you will drive down testosterone while you get ADT, PSAs become undetectable. Any of us could assume that the undetectability is the result of the radiation therapy. But the true benefit of the combination of radiation and ADT in that context really comes to be seen when the patient has got off the ADT, has recovered testosterone, and only when your testosterone has normalized or is not castrated, then we'll know what happens with your serologic changes. If you rise your PSA while you recover testosterone, that is one makeup of patient. But if you rise your PSA while you have a testosterone at the castrated level, that would be a different makeup of a patient. So do we have a sense as to when the patient recovered testosterone and whether or not if his PSA rose after recovery?  Dr. Kriti Mittal: At the time his PSA rose to 12, his testosterone was 275. Dr. Jorge Garcia: Okay, perfect. You and I would call this patient castration-naive or castration-sensitive. I know that it's semantics. A lot of people struggle with the castration-naive and castration-sensitive state. What that means really to me, castration-naive is not necessarily that you have not seen ADT before. It's just that your cancer progression is dependent on the primary fuel that is feeding prostate cancer, in this case, testosterone or dihydrotestosterone, which is the active metabolite of testosterone. So in this case, recognizing the patient had a testosterone recovery and his biochemical recurrence, which is the rising of his PSA occur when you have recovery of testosterone, makes this patient castration-sensitive. Now the PET scan demonstrates now progression of his disease. So clearly he has a serologic progression, he has radiographic progression. I assume that the patient may have no symptoms, right, from his disease?  Dr. Kriti Mittal: This patient had some low back pain at the time of this visit. So I think we can conclude he has clinical progression as well. Dr. Jorge Garcia: Okay, so he had the triple progression, serologic, clinical, and radiographic progression. The first order of business for me would be to understand the volume of his disease and whether we use the US CHAARTED definition of high volume or low volume, or whether we use the French definition for high volume from Latitude, or whether we use STAMPEDE variation for definition, it does appear to me that this patient does have high-volume disease. Why? If you follow the French, it's a Gleason score of >8, more than three bone metastases, and the presence of visceral disease, and you need to have two out of the three. If you follow CHAARTED definition, we did not use Gleason scoring, the US definition. We only use either the presence of visceral metastases or the presence of more than four bone lesions, two of which had to be outside the appendicular skeleton. So if we were to follow either/or, this patient would be high-volume in nature.  So the standard of care for someone with metastatic disease, regardless of volume, is treatment intensification, is you suppress testosterone with androgen deprivation therapy. And in this case, I'd love to hear how you do it in Massachusetts, but here, for the most part, I would actually use a GnRH agonist-based approach, any of the agents that we have. Having said that, I think there is a role to do GnRH antagonist-based therapy. In this case, degarelix, or the oral GnRH antagonist, relugolix, is easier to get patients on a three-month injection or six-month injection with GnRH agonist than what it is on a monthly basis. But I think it's also fair for our audience to realize that there is data suggesting that perhaps degarelix can render testosterone at a lower level, meaning that you can castrate even further or have very low levels of testosterone contrary to GnRH agonist-based approaches.  And also for patients maybe like this patient that you're describing, you can minimize the flare that possibly you could get with a GnRH agonist by transiently raising the DHT before the hypothalamic-pituitary axis would shut it down. So either/or would be fine with me. Relugolix, as you know, the attraction of relugolix for us right now, based upon the HERO data, is that you may have possibly less cardiovascular side effects. My rationale not to use a lot of relugolix when I need treatment intensification is quite simple. I'm not aware, I don't know if you can mitigate or minimize that potential cardiovascular benefit by adding abiraterone or adding one of the ARIs, because ARIs and abiraterone by themselves also have cardiovascular side effects. But either/or would be fine with me. The goal of the game is to suppress your male hormone.  But very important is that regardless of volume, high or low, every patient with metastatic disease requires treatment intensification. You can do an adrenal biosynthesis inhibitor such as abiraterone acetate. You can pick an androgen receptor inhibitor such as apalutamide or enzalutamide if that's the case. The subtleties in how people feel comfortable using these agents, I think, none of us – as you know, Dr. Mittal - can comment that one oral agent is better than the other one. Independently, each of these three oral agents have randomized level 1, phase III data demonstrating survival improvement when you do treatment intensification with each respective agent. But we don't have, obviously, head-to-head data looking at this.  What I think is different right now, as you know, is the data with the ARASENS data, which was a randomized phase III trial, an international effort looking at triple therapy, and that is male hormone suppression plus docetaxel-based chemotherapy against testosterone suppression plus docetaxel-based chemotherapy plus the novel androgen receptor inhibitor known as darolutamide. This trial demonstrated an outcome survival improvement when you do triple therapy for those high-volume patients. And therefore, what I can tell you in my personal opinion and when I define a patient of mine who is in need of chemotherapy, then the standard of care in my practice will be triple therapy. So if I know you are a candidate for chemotherapy, however, I make that decision that I want you to get on docetaxel upfront. If you have high-volume features, then the standard of care would not be ADT and chemo alone, it would be ADT, chemo, and darolutamide.  What I don't know, and what we don't know, as you know, is whether or not triple therapy for a high-volume patient is better, the same, equivalent, or less than giving someone ADT plus a novel hormonal agent. That is the data that we don't have. There are some meta-analyses looking at the data, but I can tell you that at the very least, if you prefer chemo, it should be triple therapy. If you prefer an oral agent, it certainly should be either apalutamide, abiraterone acetate, and/or enzalutamide. But either/or, patients do need treatment intensification, and what is perplexing to me, and I know for you as well, is that a significant proportion of our patients in North America are still not getting treatment intensification, which is really sub-optimal and sub-standard for our practice.  Dr. Kriti Mittal: Thank you, Dr. Garcia, for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. In an upcoming podcast, we will continue that discussion exploring management of de novo metastatic prostate cancer.   The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. 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. Guest 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.    

Dr. Iyad Alnahhas interviews Dr. Max Kros about his and his team's recent manuscript entitled: "Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033", published online in Neuro-Oncology in December 2022.   Read Paper

Concluding their Journey to the Centre of the Brain, Michael and Josh tackle one of the most challenging and difficult cancers in modern oncology: high-grade gliomas. All of the usual suspects are here: irrevocable, progressive disease, limited treatment options and a gulf in evidence so large it makes the Grand Canyon look like a muddy footprint. All in all, not the most optimistic of OftiM episodes, but Josh and Michael will tackle it anyway so you don't have to. And remember: always refer your fit GBM patients to a friendly neighbourhood trials unit near you!Links to studies discussed in this episode (subscription may be required):EORTC 26981-22981 NCIC CE3 (aka the “Stupp study"): https://www.nejm.org/doi/full/10.1056/nejmoa043330RTOG 0825: https://www.nejm.org/doi/full/10.1056/nejmoa1308573Brada et al: https://ascopubs.org/doi/full/10.1200/JCO.2009.27.1932?role=tabTaal et al: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70314-6/fulltextWick et al: https://www.nejm.org/doi/full/10.1056/nejmoa1707358For more episodes, resources and blog posts, visit inquisitiveonc.comFind us on Twitter @InquisitiveOncIf you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comVisit us at your new website www.inquisitiveonc.com for our latest episodes, links to resources and musings!Art courtesy of Taryn SilverMusic courtesy of AlexiAction: https://pixabay.com/users/alexiaction-26977400/Note: This podcast is for educational purposes only. If you are unwell seek medical advice Hosted on Acast. See acast.com/privacy for more information.

This episode of Lung Cancer Considered is part of our series on FDA approvals of new lung cancer therapies. Today, host Dr. Stephen Liu discusses the EMPOWER-Lung 3 regimen of the PD-1 inhibitor cemiplimab with first-line platinum doublet chemotherapy for advanced NSCLC. This regimen was approved by the FDA on November 8, 2022. His guests are Dr. Jordi Remon, a thoracic medical oncologist who had previously practiced at Hospital de Mataro in Barcelona. He is now part of the esteemed thoracic unit at Gustave Roussy in Paris and the secretary of the Lung Cancer Group of EORTC. Joining Dr. Remon is Dr. Isabel Preeshagul, a thoracic medical oncologist and Assistant Attending with Memorial Sloan Kettering. She is also the chair of the Education and Engagement Committee of the Lung Cancer Research Foundation.

CME credits: 0.75 Valid until: 30-09-2023 Claim your CME credit at https://reachmd.com/programs/cme/pembrolizumab-versus-placebo-after-complete-resection-of-high-risk-stage-iii-melanoma-long-term-quality-of-life-analysis-results-of-the-eortc-1325-mgkeynote-054-double-blinded-phase-3-trial/14454/ tbd

El Dr. Raúl Rogelio Trejo Rosales, oncólogo médico adscrito al Centro Médico Nacional “Siglo XXI”, IMSS en la Ciudad de México, México, junto con el Dr. Idelfonso Roberto De La Peña Valle, oncólogo médico adscrito al Instituto Nacional de Ciencias Médicas Salvador Zubirán en la Ciudad de México, México, nos comentan lo más destacado sobre tumores sistema nervioso central presentado durante el Congreso Anual de la Asociación Americana de Oncología Clínica 2022. Cáncer de cerebro: Abstract 2032: Revisión retrospectiva de gráficos para evaluar la proporción de pacientes con cáncer de cerebro que recibieron tratamiento dirigido vs. terapia estándar después de la secuenciación. Los pacientes se estratificaron en 1 de 3 categorías: astrocitoma, oligodendroglioma u otros subtipos raros (incluidos meningioma, ependimoma, ganglioma, xantoastrocitoma pleomórfico, tumores rabdoides teratoides atípicos, tumores glioneuronales y linfomas del SNC). Diagnóstico: Abstract e14022: Impacto de la secuenciación de próxima generación (NGS por sus siglas en inglés) en el diagnóstico de gliomas según la clasificación WHO-2016 y WHO-2021 en la práctica clínica habitual. Abstract e14009: Patrones de tratamiento y resultados de pacientes con glioma de alto grado durante la pandemia de COVID-19. Abstract 2055: Evaluó la asociación de mielosupresión (neutropenia, trombocitopenia, anemia, linfopenia) durante la quimiorradioterapia con temozolomida solo o en combinación con agentes experimentales con supervivencia libre de progresión (SLP) o supervivencia global (SG) en 2073 pacientes con glioblastoma recién diagnosticado inscritos en 5 estudios clínicos: CENTRIC, CORE, EORTC 26082, AVAglio y EORTC 26981. Abstract 2052: Se contactó a 166 centros oncológicos de todo el mundo para recuperar datos de pacientes con tumores del SNC con TRK. Los datos extraídos incluyeron demografía, histopatología, fusión del gen TRK, modalidades de tratamiento y resultados. Tumores SNC: NAVIGATE: Estudio fase II que evalúa larotrectinib en pacientes adultos y pediátricos con tumores NTRK. Su objetivo primerio es evaluar la eficacia en tumores sólidos y el secundario es evaluar eficacia y seguridad. Glioblastoma: Abstract 2067: Estudio retrospectivo realizado en el Hospital de Oncología, Centro Médico Nacional Siglo XXI. Se incluyeron pacientes histológicamente confirmados con gliobastoma tratados en un período de enero de 2015 a enero 2019. A los cuales se les sometió a cirugía seguida de temozolomida (TMZ) administrada simultáneamente con radioterapia (RT) y seguido de TMZ adyuvante vs. RT sola. ChiCTR2000028957: Estudio fase II, abierto, de un solo brazo que evaluó a pacientes con GBM confirmado histológicamente con progresión definida después de la cirugía seguida de RT y quimioterapia (QT) con temozolomida fueron elegibles para la inclusión. NCT03522298: Estudio fase II, abierto, que evaluó la seguridad, la farmacocinética y la eficacia de paxalisib en pacientes con GBM caracterizado por el estado del promotor de O6-metilguanina-metiltransferasa no metilado después de la resección quirúrgica y la terapia de quimiorradiación concomitante estándar con temozolomida. NCT03139916: Estudio fase II, abierto que evalúa bavituximab con radiación y temozolomida en pacientes con glioblastoma recién diagnosticado. NCT02152982: Estudio fase II/III, aleatorizado, doble ciego que evaluó veliparib o placebo en combinación con temozolomida adyuvante en pacientes con GBM recién diagnosticado con MGMT promotor de hipermetilación.

Dyspnø, kvalme, fatigue og eksistentiel lidelse er symptomer som hos palliative patienter ofte er udiagnosticerede og underbehandlede. I denne samtale gennemgår vi symptomerne og taler om ”Livssamtalen”.   Vores gæst Anna Weibull er speciallæge i almen medicin og har den nordiske specialistuddannelse i palliation. Christian Vøhtz er redaktør og vært. Bilag til symptomoverblik EORTC: https://vejledninger.dsam.dk/media/files/11/palliation_2014-bilag1.pdfBilag til den eksistentielle samtale EMAP: https://vejledninger.dsam.dk/media/files/18/bilag-5_-emap.pdf 

Description: Metachronous colorectal liver metastasis (CRLM) is a complex clinical situation requiring multidisciplinary management. In this episode from the Hepato-Pancreato-Biliary team at Behind the Knife, we discuss a patient presenting with metachronous CRLM and how management may change with varying clinical scenarios.  Learning Objectives: In this episode, we review the initial workup and pre-operative considerations in a patient presenting with metachronous CRLM.  We discuss key aspects of resectability of CRLM, including physiologic and hepatic fitness, biology of the disease, and technical considerations.  We review the timing and common regimens of systemic treatment for differing clinical scenarios, as well as when adjuncts to treatment may be useful (e.g., portal venous embolization).  Finally, we highlight important aspects of intraoperative and postoperative management. Hosts: Timothy Vreeland, MD, FACS (@vreelant) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at Brooke Army Medical Center Daniel Nelson, DO, FACS (@usarmydoc24) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at William Beaumont Army Medical Center Connor Chick, MD (@connor_chick) is a PGY-5 General Surgery resident at Brooke Army Medical Center Lexy (Alexandra) Adams, MD, MPH (@lexyadams16) is a PGY-4 General Surgery resident at Brooke Army Medical Center Beth (Elizabeth) Carpenter, MD (@elizcarpenter16) is a PGY-3 General Surgery resident at Brooke Army Medical Center  Links to Papers Referenced in this Episode: NCCN Guidelines for Colon Cancer https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases. Clin Cancer Res. 2019 Oct 1;25(19):5843-5851. doi: 10.1158/1078-0432.CCR-19-0863. Epub 2019 Jun 20. PMID: 31221662; PMCID: PMC6774854. https://pubmed.ncbi.nlm.nih.gov/31221662/ Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. doi: 10.1016/S1470-2045(13)70447-9. Epub 2013 Oct 11. PMID: 24120480. https://pubmed.ncbi.nlm.nih.gov/24120480/ FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306-15. doi: 10.1016/S1470-2045(15)00122-9. Epub 2015 Aug 31. PMID: 26338525. https://pubmed.ncbi.nlm.nih.gov/26338525/ Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14. PMID: 30552157; PMCID: PMC6656450. https://pubmed.ncbi.nlm.nih.gov/30552157/ Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23. PMID: 25538173. https://pubmed.ncbi.nlm.nih.gov/25538173/ Recommended Additional Podcasts on CRLM: The AHPBA Podcast: 1.     Episode 1: Dr. Jean Nicolas Vauthey - Colorectal Liver Metastases (https://podcasts.apple.com/us/podcast/episode-1-dr-jean-nicolas-vauthey-colorectal-liver/id1501441845?i=1000467381474) 2.     Episode 12:Dr D'Angelica - Colorectal Liver Metastases and Hepatic Artery Infusion Pumps (https://podcasts.apple.com/us/podcast/episode-12-dr-dangelica-colorectal-liver-metastases/id1501441845?i=1000521718184) Behind the Knife: 1.     Surgical Oncology-Hepatic Artery Infusion Pump (https://podcasts.apple.com/ye/podcast/surgical-oncology-hepatic-artery-infusion-pump/id980990143?i=1000525833877) Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

Dr. Shannon Westin and Dr. Antonio Di Meglio discuss the issue of fatigue among cancer survivors.   Transcript [MUSIC PLAYING] Speaker 1: The guest on this podcast episode has no disclosures to declare. Shannon Westin (Dr. Westin): Hello, everyone. And welcome to another episode of JCO After Hours. This is our podcast where we get in depth with different authors and experts about wonderful manuscripts that are being published in the Journal of Clinical Oncology. And today it is my great pleasure to be accompanied by Dr. Antonio Di Meglio, who is a Medical Oncologist and a Physician Scientist at the Breast Cancer Survivorship Research Program in Gustave Roussy in France. So welcome, Dr. Di Meglio. Dr. Antonio Di Meglio (Dr. Di Meglio): Thank you so much for having me here today. Dr. Westin: We're so excited to have you. We're going to be talking about your article, which is due to be published January 21, 2022, in the Journal of Clinical Oncology titled “The Development and Validation of a Predictive Model of Severe Fatigue After Breast Cancer Diagnosis: Toward a Personalized Framework in Survivorship Care.” And before we get started, I would just note that none of the guests have any relevant conflicts to disclose. With that, let's get into it. I was so excited to read this paper because this such a critical problem for our patients. And I'm a gynecologic oncologist, but this goes across all—surgical, medical, any field that we could even think of. So why don't you start off by telling us what led you to explore the problem of cancer-related fatigue? Dr. Di Meglio: Cancer related fatigue is one of the most troublesome and prevalent symptoms among cancer survivors and including breast cancer survivors. So several reports reported on the prevalence of cancer-related fatigue reporting up to 50% of patients in some studies with fatigue after cancer and the end of treatment. But what we know is that at least one in three cancer survivors experience fatigue symptoms at some point over time. In addition, we do know that fatigue is particularly distressing and impactful as it can impact on daily living and functioning and overall quality of life. Also, there's an important impact on social function and return to work after cancer and adherence to oral therapies, especially in the age event setting in breast cancer survivors. Finally, we also know that fatigue is often inadequately addressed and often neglected because of lack of time, lack of resources. Definitely, we should do more in the clinic for our patients struggling with fatigue. Dr. Westin: This is such an important issue. I think the elephant in the room here is how do we grade this and how do you advocate for a busy clinician in the clinic seeing 30, 40, 50 patients in a day. How do we really assess this? What's the best way to determine if somebody has cancer-related fatigue or is at risk? Dr. Di Meglio: Thank you for this important point. In clinical research, we do have a number of instruments that we can use to grade fatigue, including the European Organization For Research and Treatment of Cancer, Quality of Life Questionnaires that are the questionnaires that we used in our study. These are instruments that our patient reported. So we really can hear patient voices and patient perspectives in terms of their own symptoms. And some of the items that we use, for example, for cancer-related peak do not take much time to be asked also in a basic clinic. For example, we did use the EORTC QLQ Questionnaire C30 to score global fatigue. So we basically asked patient three questions: whether they needed to rest, they felt weak, or they felt tired, typical week. And these gave us the score of what we called global fatigue. There's also other instruments and companion models that we can use to assess more specifically dimensions of fatigue, including the physical, emotional, and cognitive dimension of fatigue. It is true that in our busy day in clinics, this may not be easily implementable. But what I believe is that if we never ask patients the right questions, patients will never tell us the right answers that we can proactively use to address the symptoms. So even just assessing fatigue in a general way, asking whether their energy levels changed over the past weeks, if they know that any change that was related to the treatment or any tiredness that was not really related to their usual activities or that was impactful on daily activities, this should trigger clinicians to ask more and more and to find solutions for the problem. So just ask the questions, even though the assessment may not be comprehensive and extensive, but this can be very important and meaningful for the patients. Dr. Westin: I think that's a really critical point because using validated instruments is obviously our aspirational goal and our attempted standard of care, but on a day in and day out clinic, it can be hard to have patients filling out a survey or something that may take a longer time. So I think that's a critical point is pull out these critical questions so that you can identify these issues and address them for your patient. When we're talking about grading fatigue, say in the clinic, would you recommend maybe choosing one? How long do these types of assessments take? Is this something feasible for a busy oncologist in clinic? Dr. Di Meglio: So definitely our study calls a little bit for the implementation of these instruments that are being used in mostly in clinical research over the past decades, also in the clinical practice. These are patient reported instruments that really can give us a sense of how impactful fatigue is in daily living and functionality. And when we grade fatigue using this instruments such as the EORTC scores, we can really capture fatigue that is defined as severe, meaning fatigue that really impacts on quality of life and needs to be absolutely addressed by clinicians and needs interventions urgently. Dr. Westin: That makes a lot of sense. Why don't we get into a little bit more around your study using these specific instruments? Like what was the patient population? Run us through that. Dr. Di Meglio: So this study was performed using CANTO data. CANTO is a longitudinal cohort of breast cancer survivors. Patients that were initially diagnosed with Stage 1, 2, and 3 breast cancer. It's a French cohort that enrolled patients across 26 centers in France starting in 2012. And at this point, the cohorts included over 10,000 patients, and this study was performed using a first split of the cohort for the development models that included around 6,000 patients overall, and then 3000 patients for the validation of these models. So the availability of data of fatigue was really the driver of the patient population that we used for this study. So we used all available questionnaires of EORTC QLQ-C30 therapy, to which we assessed our primary outcome of interest, which was global fatigue. CANTO has a first assessment at baseline, that is a breast cancer diagnosis, meaning before the initiation of any cancer treatment. Meaning surgery, chemotherapy, radiation therapy, therapy of any type. Then we perform longitudinal assessment at one year, two years, four years after diagnosis. There is a fifth assessment at five years after diagnosis for which data are not mature yet, but for the present study, we use data until four years after diagnosis. So our interest was to understand which are the risk factors for severe fatigue, primarily at two years after diagnosis. Then we also developed and validated models for severe fatigue at four years after diagnosis. So our interest was to identify a population of patients that since diagnosis can be flagged as being at high risk of developing severe fatigue after diagnosis and of course after treatment for breast cancer. This is a population of early-stage breast cancer survivors. So I really want to highlight that these models were developed and validated for survivors that are free of cancer at the time of fatigue assessment. So whether they experience cancer recurrence, metastasis, second cancers, they exit cohort. So this is purely early stage survivors of breast cancer. Dr. Westin: Thank you for that clarification. And I think it is important to really focus in on these populations because we are going to see differences in the occurrence of fatigue across patients that are actively receiving treatment in the continuum of recurrence or later in survivorship. So thank you for that clarification. I think that that really makes a lot of sense. And this is a population that's extremely large and very critical to our management. So why don't you tell us a little bit about what were some of the factors that you found to be associated with severe fatigue in your cohort? Dr. Di Meglio: So our models allowed us to identify a number of factors that are risk factors for severe fatigue after breast cancer diagnosis. So first of all, the most consistent and the strongest factors that was identified as associated with post-treatment fatigue was pre-treatment fatigue. So patients that are already severely fatigued at diagnosis have much higher likelihood of reporting severe fatigue also years after diagnosis. This was identified as a risk factors also in previous literature as it may set stage for post-treatment fatigue because maybe there are biological disruptions or bio-behavioral disruptions that are already present at the moment of diagnosis. So they keeping there and they put patients at higher risk of post-treatment fatigue. In addition to this, we found that clinical factors such as younger age was associated with high risk of fatigue after treatment. And there are also behavioral risk factors.  Patients that are current smokers at the time, active smokers at the time of the diagnosis, as well as patients with a higher body mass index. They are all at higher risk of persistent, severe fatigue after diagnosis. Finally, we also identify concomitant symptom clusters that are associated with a higher risk of severe fatigue. And these include emotional distress and particularly anxiety, insomnia. So sleep disturbances and pain at the moment of diagnosis. These are the risk factors that emerged for the models of severe fatigue at year two after diagnosis. But when we look further in to the risk factors of fatigue at year four after diagnosis, we consistently identified premenopausal status that is very consistent with younger age and also received of hormonal therapy. So our assumption was that longer these patients are into hormonal therapy, the higher the risk of severe fatigue becomes. So even though our models at Tier 4 are to be considered exploratory, we believe that they give us an additional insight into which treatment related factors would be associated with higher risk of fatigue. Dr. Westin: You'll have to forgive me because my knowledge of early breast cancer is very minimal. So for these patients, did any of them receive chemotherapy and was that at all relevant or is this a population that generally got maybe surgery and hormonal therapy? Dr. Di Meglio: So in the population that we study and consistent with the stage distribution, over 50% of the patients received chemotherapy. Almost 80% and more received hormonal therapy. So we really investigated the impact of all treatment types on the risk of fatigue. And we did find a differential impact of different treat modalities on the risk of fatigue.  I liked this in the paper because this is Year 1 model while our main interest was Year 2 after diagnosis models. But we did find an impact of chemotherapy on the risk of fatigue at one year after diagnosis, meaning the closest time point that we have to the end of primary treatment, including chemotherapy. And this effect seems to produce over time, and we don't find it in models at Year 2 and Year 4 anymore. So it's less consistent and it's not confirmed invalidation models. In contrast, the impact of hormonal therapy was much stronger at Tier 2 was confirmed at Tier 4. So this gives us the sense that the longer patients are on hormonal therapy, the higher risk of severe fatigue becomes for them. And this is also consistent with previous data from other literature. For example, Pat. A Ganz in The Mind-Body Study had demonstrated that hormonal therapy can delay the recovery from treatment-related symptoms that are usually associated with chemotherapy. And in a previous study using the CANTA cohort, we also had found an impact of hormonal therapy on the recovery of symptoms and functions that usually get better over time, for example, emotional function or future perspectives whose recovery seems to be delayed among patients that receive hormonal therapy. Dr. Westin: Well, this is great, understanding who might be at risk and trying to identify these patients. I guess the natural question is next. Like what do we do? What are our available options to treat cancer-related fatigue or even prevent it? Dr. Di Meglio: I think this is a great point and that definitely leads me to trying to understand and to explain what is the implementation of our models in clinic. So what we envision would be a clinical care setting where our models would aid clinicians to be more aware about the problem of fatigue and about ways that we have to better describe fatigue among our patients and better identify its risk factors. So let's imagine that we have an incoming new patient in our clinic and we assess the risk of severe fatigue in this patient after treatment. By assessing risk factors, we also assess fatigue at the moment of diagnosis. And we do know that in this analysis, we found that almost 25% of patients present already with severe fatigue diagnosis, and a patient like this needs to be already treated for the symptoms that he or she is reporting. So we do have now available interventions to treat fatigue when it's already present. So first of all, increasing physical activity. We also have psychosocial interventions, including cognitive behavioral therapy and psychoeducational therapies that we know that work for cancer-related fatigue and some mind-body interventions, such as yoga demonstrated some activity for cancer-related fatigue. Other approaches include mindfulness based approaches or acupuncture that can be offered to patients that already present with severe fatigue and diagnosis, particularly also the assessment of all concomitant conditions, such as nutritional imbalances should be performed in detail at the moment of diagnosis. In contrast, we might find a patient that doesn't have symptoms of severe fatigue at the moment of diagnosis, but definitely our models can increase the awareness of the risk factors and highlight a way to recognize symptoms that can hurl out the onset of fatigue and facilitate the management of risk factors and the referral to dedicated consultations or to dedicated specialists that can take care of such risk factors. In fact, the majority of risk factors that we identified are modifiable, such as we can address as tobacco use. We can address overweight and obesity as well as we can address specific symptom clusters that usually come in conjunction with fatigue, sleep problems, pain, emotional distress. We do have interventions available for all these symptoms. Of course, there is an important question there arises here, that is by addressing all three factors, is fatigue preventable at this point. I am not sure that we have the answer yet for this question at this point, but definitely by addressing risk factors, by addressing behavioral problems, we are addressing survivorship problems in a more comprehensive way. That is the direction in which survivorship care should probably go today. So as next steps, definitely we should look towards the implementation of risk models in clinical practice towards planning more meaningful prevention trials for problems such as cancer-related fatigue. And in addition, I believe that cancer-related fatigue is just an example of very common and prevalent and distressing symptoms that are not often taken care of or sufficiently taken care of in the clinic. So this can serve as a case study, as a model to expand our no also of other symptoms and of other survivorship issues that our patients and survivors may face. Dr. Westin: Well, I just want to commend you. These are really such exciting work, and I know it's something that will be implemented in the breast cancer community but also beyond. And I'm hoping that some of our other cancer-type survivorship experts are listening right now and getting inspired by your work. So we can look at this in other tumor types and really help implement this across the world. So thank you so much again for your amazing work. Thank you so much for taking the time to meet with me today, and best of luck in moving this forward. Dr. Di Meglio: Thank you so much, Dr. Westin. It was great to be here with you today. Dr. Westin: Thank you so much to all our listeners. We are always so grateful that you tune in and we can't wait to bring you discussion of our next manuscript. Have a great one. [MUSIC PLAYING] 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. guest 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.  

La Dra. Patricia Cortés, oncólogo médico adscrita al CMN “20 de Noviembre”, ISSSTE, en la Ciudad de México, México junto al Dr. Juan Pablo Molina, oncólogo médico adscrito al Hospital México CCSS en San José, Costa Rica, nos comentan sobre lo más destacado en tumores ginecológicos, presentado en el Congreso Anual de la Sociedad Europea de Oncología Médica, resaltando los siguientes estudios: KEYNOTE-826:Estudio fase III, aleatorizado, doble ciego y controlado, el cual evaluó la eficacia y seguridad del tratamiento de 1L con pembrolizumab + quimioterapia vs. placebo + quimioterapia en pacientes con cáncer de cuello uterino persistente, recurrente o metastásico. Los objetivos primarios de evaluación fueron la supervivencia libre de progresión (SLP) y la supervivencia global (SG). EORTC-1508:Estudio fase II, aleatorizado, donde el objetivo fue evaluar la eficacia (a través de la SLP a los 6 meses) y la seguridad de 5 tratamientos diferentes con atezolizumab, bevacizumab y/o ácido acetilsalicílico en pacientes con cáncer de ovario avanzado recurrente/resistente al platino con el fin de seleccionar los tratamientos óptimos para un mayor desarrollo en fase III. Relacorilant/NCT03776812:Estudio fase II, aleatorizado, de etiqueta abierta, que evaluó 3 brazos de tratamiento de relacorilant + nab-paclitaxel. El objetivo primario fue evaluar la SLP en 178 pacientes con cáncer de ovario, de trompas de Falopio o peritoneal primario resistente al platino recurrente tratadas con regímenes intermitentes o continuos de relacorilant + nab-paclitaxel vs. pacientes tratadas con nab-paclitaxel solo. OCTOVA: Estudio fase II, aleatorizado, de etiqueta abierta, que evaluó olaparib, quimioterapia u olaparib y cediranib en 139 pacientes con cáncer de ovario resistente al platino. Las pacientes fueron aleatorizadas 1:3 en los grupos de tratamiento: olaparib solo, olaparib y cediranib, considerando como grupo de control los tratados con paclitaxel. El objetivo de este estudio fue comparar la eficacia de los 3 tratamientos y observar la tolerabilidad de cada uno, incluida la calidad de vida de las pacientes. OReO: Estudio fase IIIb, multicéntrico, aleatorizado, doble ciego, controlado con placebo, que evaluó la eficacia y tolerabilidad de retratamiento de mantenimiento con olaparib vs. el placebo correspondiente en 194 pacientes con cáncer de ovario epitelial no mucinoso, incluidas las pacientes con cáncer primario de peritoneo y/o de trompas de Falopio. NRG-GY004: Estudio fase III, aleatorizado, de etiqueta abierta, que evaluó la comparación entre olaparib como agente único o en combinación con cediranib + quimioterapia estándar basada en platino en 579 pacientes con cáncer de ovario, de trompas de Falopio o primario peritoneal primario sensible al platino recurrente. EMPOWER-Cervical 1: Estudio fase III, aleatorizado, de etiqueta abierta que evaluó el tratamiento de cemiplimab vs. la elección de quimioterapia del investigador en 608 pacientes con carcinoma de cuello uterino recurrente o metastásico, el objetivo primario del estudio fue la SG.

La Dra. Patricia Cortés, oncólogo médico adscrita al CMN “20 de Noviembre”, ISSSTE, en la Ciudad de México, México junto al Dr. Juan Pablo Molina, oncólogo médico adscrito al Hospital México CCSS en San José, Costa Rica, nos comentan sobre lo más destacado en tumores ginecológicos, presentado en el Congreso Anual de la Sociedad Europea de Oncología Médica, resaltando los siguientes estudios: KEYNOTE-826: Estudio fase III, aleatorizado, doble ciego y controlado, el cual evaluó la eficacia y seguridad del tratamiento de 1L con pembrolizumab + quimioterapia vs. placebo + quimioterapia en pacientes con cáncer de cuello uterino persistente, recurrente o metastásico. Los objetivos primarios de evaluación fueron la supervivencia libre de progresión (SLP) y la supervivencia global (SG). EORTC-1508: Estudio fase II, aleatorizado, donde el objetivo fue evaluar la eficacia (a través de la SLP a los 6 meses) y la seguridad de 5 tratamientos diferentes con atezolizumab, bevacizumab y/o ácido acetilsalicílico en pacientes con cáncer de ovario avanzado recurrente/resistente al platino con el fin de seleccionar los tratamientos óptimos para un mayor desarrollo en fase III. Relacorilant/NCT03776812: Estudio fase II, aleatorizado, de etiqueta abierta, que evaluó 3 brazos de tratamiento de relacorilant + nab-paclitaxel. El objetivo primario fue evaluar la SLP en 178 pacientes con cáncer de ovario, de trompas de Falopio o peritoneal primario resistente al platino recurrente tratadas con regímenes intermitentes o continuos de relacorilant + nab-paclitaxel vs. pacientes tratadas con nab-paclitaxel solo. OCTOVA: Estudio fase II, aleatorizado, de etiqueta abierta, que evaluó olaparib, quimioterapia u olaparib y cediranib en 139 pacientes con cáncer de ovario resistente al platino. Las pacientes fueron aleatorizadas 1:3 en los grupos de tratamiento: olaparib solo, olaparib y cediranib, considerando como grupo de control los tratados con paclitaxel. El objetivo de este estudio fue comparar la eficacia de los 3 tratamientos y observar la tolerabilidad de cada uno, incluida la calidad de vida de las pacientes. OReO: Estudio fase IIIb, multicéntrico, aleatorizado, doble ciego, controlado con placebo, que evaluó la eficacia y tolerabilidad de retratamiento de mantenimiento con olaparib vs. el placebo correspondiente en 194 pacientes con cáncer de ovario epitelial no mucinoso, incluidas las pacientes con cáncer primario de peritoneo y/o de trompas de Falopio. NRG-GY004: Estudio fase III, aleatorizado, de etiqueta abierta, que evaluó la comparación entre olaparib como agente único o en combinación con cediranib + quimioterapia estándar basada en platino en 579 pacientes con cáncer de ovario, de trompas de Falopio o primario peritoneal primario sensible al platino recurrente. EMPOWER-Cervical 1: Estudio fase III, aleatorizado, de etiqueta abierta que evaluó el tratamiento de cemiplimab vs. la elección de quimioterapia del investigador en 608 pacientes con carcinoma de cuello uterino recurrente o metastásico, el objetivo primario del estudio fue la SG.

Recent trials in sarcoma sought to determine the impact of neoadjuvant therapies and histologic/genomically specific treatments. Valerie Grignol, MD, Gabriel R. Tinoco Suarez, MD, and Alessandro Gronchi, MD, FSSO, discuss the following recent trials will. The EORTC-62902:STRASS trial evaluated the impact of neoadjuvant radiotherapy for retroperitoneal sarcoma on abdominal recurrence-free survival. A study by the Italian, Spanish, French and Polish Sarcoma groups sought to determine if histology-tailored neoadjuvant chemotherapy was superior to standard anthracycline plus ifosfamide for high-risk extremity and trunk soft tissue sarcoma for disease-free and overall survival. The NAVIGATOR study evaluated the PDGFRA inhibitor avapritinib and its activity in D842V-mutant gastrointestinal stromal tumors. Lastly the INVICTUS study evaluated the impact of further line therapy ripretinib, a switch-control tyrosine kinase inhibitor, on progression-free survival in advanced gastrointestinal stromal tumors. Valerie Grignol, MD - Member, SSO Sarcoma Disease Site Work Group, Assistant Professor of Surgery, The Ohio State University Gabriel R. Tinoco Suarez, MD - Medical Oncologist and Clinical Assistant Professor - Division of Medical Oncology at The Ohio State University Alessandro Gronchi, MD, FSSO - Chair Sarcoma Service - Department of Surgery; Fondazione IRCCS Istituto Nazionale dei Tumori (Milan, Italy)

Featuring an interview with Dr Arjun Balar, including the following topics: Phase III VISION study: Lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (PC) (0:00) Updated safety outcomes from the EORTC 1333/PEACE III trial: Effect of adding bone-protecting agents (3:44) First results from the Phase III PEACE 1 study evaluating abiraterone acetate with prednisone and/or local radiation therapy for de novo metastatic castration-sensitive PC (5:09) Update on darolutamide tolerability: Outcomes with aggressive hormonal therapy for high-risk localized PC  (7:35) Bladder-sparing therapy with pembrolizumab, gemcitabine and concurrent hypofractionated radiation therapy for muscle-invasive bladder cancer (MIBC) (9:17) Results from the Phase II HCRN GU16-257 trial: Gemcitabine/cisplatin with nivolumab and selective bladder sparing for patients with MIBC (12:00) Long-term outcomes from the KEYNOTE-052 trial assessing first-line pembrolizumab for cisplatin-ineligible patients with advanced urothelial cancer (15:02) First-line maintenance therapy with avelumab for advanced urothelial cancer: Subgroup analysis of the JAVELIN Bladder 100 trial (17:19) Phase III CheckMate 9ER trial: Outcomes by baseline disease characteristics with nivolumab and cabozantinib for advanced renal cell carcinoma (RCC)  (18:29) Results from the Phase III KEYNOTE-564 study assessing pembrolizumab as postnephrectomy adjuvant therapy for patients with RCC  (20:16) Pembrolizumab with axitinib as first-line therapy for advanced RCC: Results from a 42-month follow-up of the KEYNOTE-426 trial (22:26) Updates on tyrosine kinase inhibitor and immune checkpoint inhibitor combination therapy and other novel agents for patients with RCC (24:07) Expert perspectives on advances in the treatment of genitourinary cancers (26:30) CME information and select publications

Dr. Mitul Gandhi, medical oncologist-hematologist at Virginia Cancer Specialists of the US Oncology Network, highlights therapeutic advances in multiple myeloma featured at the 2021 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Mitul Gandhi, a medical oncologist specializing in hematologic malignancies at Virginia Cancer Specialists, which is part of the US Oncology Network. Dr. Gandhi will discuss therapeutic advances in multiple myeloma featured at the 2021 ASCO Annual Meeting. He reports no conflicts of interest relating to our discussion today, and full disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Gandhi, welcome to the ASCO Daily News podcast. Dr. Mitul Gandhi: Thank you for having me. ASCO Daily News: Let's first look at the OPTIMUM MUKnine trial. It's Abstract 8001. And it reported high overall response rates in patients with ultra high-risk multiple myeloma with Dara-CVRd induction therapy. What are your takeaways from this study, Dr. Gandhi? Dr. Mitul Gandhi: Sure. So, the OPTIMUM study was conducted by the UK group, and it's noteworthy for several reasons. The way they had constructed the trial, they designed and developed a platform primarily to enrich for a predefined subset of very high-risk individuals, whether it was through a set of genetic assessment or with central gene expression profiling. And the way the trial was conducted, while patients were waiting to ascertain the results of the gene expression profiling (GEP) they could receive two cycles of bridging therapy. Once those results were furnished or they met the cytogenetic risk criteria, patients who subsequently consented to the intervention protocol which was a dose intensified regimen, five drug regimen, incorporating daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone. So, patients would receive induction for up to six cycles, and that would include the two cycles of potential bridging therapy as GEP was being evaluated on an every 21 day basis. And then this was followed by a modified conditioning regimen consisting of high-dose melphalan at 200 milligrams per meter squared along with weekly bortezomib which was continued even following autologous stem cell rescue, really until count recovery. Subsequently, patients received an additional six cycles of daratumumab, bortezomib, revlimid, or lenalidomide followed by 12 cycles of daratumumab and rituximab until progression. This was a complex study design with an intensified induction consolidation and maintenance phase, but it did yield a impressively high OR rate, or overall response rate, at 94% with very good partial response or greater seen in 77% after assessment following autologous transplantation, including 46% complete response (CR). And of those with CR, they had identified 63% achieving MRD negativity as well. And I think the authors should be commended for one, enriching a high-risk subset of patients both on conventional cytogenetics and/or GDP, and then two, utilizing the most active agents that we currently have to elicit high responses and then to consolidate on those following transplant. I think some of the take homes from the study are the ability to demonstrate feasibility of central genomic risk stratification related to more precisely identify and select high-risk patients as this is kind of an area of unmet need of where to augment therapy appropriately. I think it's still a question whether or not this is the exact dose intensified regimen that's going to elicit the best long-term outcomes in these highest risk patients and whether or not the conventional surrogates for a long-term progression-free survival (PFS) benefits such as MRD really apply to this as there is some controversy regarding that. Nonetheless, I think this offers a kind of a reproducible platform that can be emulated to identify the highest risk patients. You can do that prospectively, and then to selectively incorporate the most active agents and potentially the next generation of novel agents, including immunomodulators, cellular therapy, bi-specific antibodies earlier in the treatment course, and really try to elicit the deepest initial response and hopefully see that translate into longer term durable control. So, this was a complex study design that was impressively executed, and again with an ability to enrich for the highest risk subsets. ASCO Daily News: Excellent. Thanks for sharing your takeaways from the OPTIMUM trial. Well let's focus on the phase II CARTITUDE-2 study. That's Abstract 8013. This study reported that deep and early responses were yielded with a single infusion of cilta-cel in patients who had received one to three prior lines of therapy for multiple myeloma. What are your thoughts on this trial? Dr. Mitul Gandhi: So, Dr. Usmani presented the CARTITUDE-2 update on behalf of his co-collaborators. And the listeners probably are aware of some of the preliminary data that was presented at ASH as well in 2020, but this is a phase I/II protocol. Currently the phase II data are being presented with a proprietary CAR T platform which has two BCMA single domain antibodies on the CAR T construct along with a co-stimulator domain. And as kind of summarized in the title, the single dose was infused. So, amongst 113 patients who were initially recruited, 97 ultimately were treated with some fallout attributed to progressive disease. Like many of the other CAR T studies, this was a uniformly high-risk and heavily pretreated population. Median age was 61. High-risk cytogenetics were in 23% of patients. And there was about 20% of patients who had harbored plasma cytomas as well. Response rates were impressively high at almost 98%, and 67% obtaining a stringent complete response (CR). Much like the other CAR T experience, response continued to deepen over time. And encouragingly, duration of response was actually not reached time of presentation. Kind of amplifying the depth of response, of the patients assessable for MRD, 93% had achieved an MRD negative state at a sensitivity of 10 to the minus fifth cells, leading to a 12-month PFS of 77% and an OS of 89%. So, these are all welcome numbers and response data, again, in a heavily pretreated population who have been exposed to what we believe all the more active agents in the disease. In parallel with kind of response, with particularly with CAR T is the toxicity data. And encouragingly, while CRS, or cytokine release syndrome, which is typified in CAR T therapy was seen in about 95% of patients, only 4% had grade 3 to 4 CRS. So, on the whole, quite manageable. Median time to onset was 7 days with duration of 4 days and resolved with appropriate medical therapy, including tocilizumab. They did report one patient who had grade 5 CRS with hemophagocytic lymphohistiocytosis (HLH) with the remainder, I was summarizing kind of the low level of grade 3, 4 experience. There was additionally neurotoxicity and 21%, with 10% having grade 3 or higher. Again, resolved with supportive care measures. So, in totality this builds on the CAR T experience with high response rates, deep response, rates including achievement of stringent CR and high rates of MRD negativity with only a single dose of CAR T cells infused, again amplifying the efficacy of this platform on a heavily pretreated population and potentially allowing for extended treatment-free intervals as well or options for retreating in people who don't achieve MRD with a manageable toxicity profile at experienced centers. Certainly there's still work that's going to be done to better delineate the extent of CRS and how to appropriately treat that along with the neurotoxicity, but along with several other abstracts presented at this meeting and meetings prior, builds on the CAR T experience, knowledge rapidly coming to the forefront in myeloma therapy. ASCO Daily News: Great. So, some good developments for previously treated patients. Well, now I'd like to focus on newly diagnosed multiple myeloma. Let's look at the CARDAMON trial, Abstract 8000, and the FORTE trial, Abstract 8002. These studies explored novel therapies that are emerging for newly diagnosed multiple myeloma. So in their presentations, these trial investigators seem to question the value of standard of care autologous stem cell transplant (ASCT). So do you think these new data call into question the advantages of the up front ASCT approach in newly diagnosed multiple myeloma? Dr. Mitul Gandhi: That's a great question. And as providers in the myeloma community know, there's still an ongoing debate whether or not to ubiquitously apply a high dose melphalan conditioning and stem cell rescue across the spectrum of all patients with myeloma who are transplant eligible or reserving it for certain patients or not. Some of this is borne out of saving unnecessarily aggressive therapy, who would otherwise achieve an excellent response of induction. Along with some concern for secondary genotoxic effects imparted by the melphalan itself and perhaps propagating more biologically aggressive subclones. And to that end, these two abstracts explored whether or not transplant-free approaches would be feasible. So, the CARDAMON study enrolled 281 patients where all patients received kyprolis, cyclophosphamide, and dexamethasone for four cycles, and of those patients achieving at least a partial response (PR), they were subsequently randomly assigned to continuous KCd or autologous stem cell transplant. And what the authors concluded, KCd induction followed by KCd maintenance was not inferior to autologous stem cell transplant with PFS at 2 years measured at 70% versus 76%, and that difference meeting the criteria that was prespecified in terms of their confidence interval for noninferiority. So, on the surface you could argue based on the results that were presented that there was equivalence. But a few caveats that are important to bring up, the first was that follow-up was short. It was only two years, and so it's very plausible that with longer follow up, the noninferiority that was seen may not be borne out with extended follow up. The other point the author's note was that MRD negativity was higher in the autologous stem cell group at 53% compared to 35.8% of the non-transplant group. And various studies have reported this to be a reasonable surrogate for long-term PFS, not always. And so again highlights the fact that with longer follow up, we may see a separation of the curves. Their subset analyses did not demonstrate any obvious areas, rather a subset of patients that would have derived preferential benefit, although the numbers were quite small. So, while an initial conclusion may be that there was a relative equivalence for a transplant-free approach, I'd argue that it's probably still a bit premature to make that conclusion and noninferiority may not be identical with longer follow up. And additionally, this probably is an induction regimen that is not as commonly employed in the U.S. But it does again help to the body of literature regarding this question of transplant for all versus not, although there may be hopefully more discriminatory power to see where it would be beneficial. The FORTE study presented by Dr. Gay and her colleagues was a bit larger at 464 patients and slightly different. Patients were randomly assigned to one of three arms, carfilzomib plus cyclophosphamide plus dexamethasone for four cycles induction followed by autologous stem cell rescue, carfilzomib, lenalidomide, dexamethasone induction for four cell cycles followed by autologous stem cell rescue, or carfilzomib, lenalidomide, dexamethasone without autologous stem cell for 12 cycles. So, those were the three arms, and then there was a second randomization to lenalidomide versus lenalidomide plus carfilzomib maintenance. Patients were prespecified in terms of their cohorts of high-risk, standard risk, or the so-called double hit which was people, patients rather, harboring two high-risk cytogenetic features. And so what the authors concluded that across the board, the arm containing carfilzomib, lenalidomide, dexamethasone with autologous stem cell rescue demonstrated superior PFS compared to all of the other, rather, the other two arms. And similarly intensification of maintenance incorporating kyprolis plus revlimid resulted in superior 3 year PFS compared to revlimid alone in 90% versus 73%. So what do we take away from this? Well, it's not a conventional induction approach in the U.S., with RVd still predominantly being used, particularly after the endurance data was presented at last year's ASCO showing equivalence of a bortezomib induction strategy versus carfilzomib strategy. It does support and lend credence to the use of high dose melphalan autologous stem cell rescue as patients who are in this arm seem to enjoy a more longer and durable progression-free survival across all subsets, including standard risk, high-risk, and the double hit strategy. So there wasn't any particular subset that could be identified that would have performed equally well with KRd alone without autologous stem cell rescue. Putting these two abstracts together, I would still argue that there remains a very important role for our high dose melphalan and autologous stem cell rescue currently an induction, rather following induction, in appropriately selected patients. And while we may not have identified patients on preselected criteria based on their cytogenetic risk, it's conceivable that we might identify response based criteria, whether it's MRD or otherwise, to perhaps see who may be able to abstain from transplantation. And there are several protocols that are actively accruing, some that have been preliminarily presented, and some that will be presented in subsequent meetings that might lend evidence to this. But for now based on the data sets that were presented at this year's meeting at ASCO, there still seems to be support for use of high dose melphalan and autologous stem cell rescue. ASCO Daily News: Right. Well staying with the issue of transplantation, for over a decade investigators have been exploring the curative ability of alloHCT in select patients with high-risk multiple myeloma. Fast forward to 2021 and the phase II double blind, placebo controlled, blood and marrow transplant clinical trials network 1302 trial. That's Abstract 7003. This study found that when performed with a reduced intensity conditioning regimen of bortezomib, fludarabine, and melphalan, alloHCT was safe in patients with high-risk multiple myeloma. What are your thoughts on this, and do you anticipate further research on the role of alloHCT in patients with multiple myeloma and high-risk features? Dr. Mitul Gandhi: So, this is an interesting abstract presented by Dr. Nishihori and her colleagues specifically looking at the role of ixazomib maintenance following a reduced intensity conditioning regimen of fludarabine, melphalan, and bortezomib in patients with high-risk myeloma. So this study was a phase II study enrolling patients under the age of 70 with high-risk myeloma defined by cytogenetics, or presence of plasma cell leukemia, or relapse within 24 months of an autologous stem cell transplant, which has been identified as a prognostic factor independent of baseline risk of poor outcomes, with the goal of administering the reduced intensity conditioning followed by HLA matched donor unmanipulated graft with methotrexate and tacrolimus GVHD prophylaxis, and starting at day 60, randomization ixazomib versus placebo maintenance. It should be noted that the goal initially was to enroll 110 patients, but ultimately only 57 patients were accrued over the course of 4 years from 2015 to 2018, 52 ultimately receiving an allogeneic HCT and 43 proceeding to maintenance. And so this in and of itself highlights the challenges of running an alginate transplant trial in myeloma mainly because sick patients may be by the point where allogeneic transplant is being entertained or inability to achieve sufficient disease control in order to pursue the transplant. But with respect to the study itself, they reported a PFS and overall survival (OS) outcome at 24 months, of 52% and 85% respectively, with transplant-related mortality at a respectable 11%. So in context of the small studies that had previously been reported in this space of allo SCT and myeloma, this was improved treatment-related mortality related to the procedure itself. With respect to the question at hand regarding the role of ixazomib maintenance, interestingly they showed no difference in PFS, with ixazomib versus placebo at 55% and 59% and OS at 95% and 87%. In terms of the toxicity, it was not trivial. Grade 3 to 4 acute GVHD at day 100 was 9.5% in the ixazomib arm, 0% in the placebo arm. And chronic GVHD was 69% versus 64%. So, where do we take all of this data in context? I think there is a signal of lower transplant-related mortality compared to historical controls, and so it probably speaks to the improved ability to identify patients and also get them through transplant with this modified conditioning. The follow up, however, was abbreviated, and so there may be increased relapse over time as well. In terms of where does this fit in the armamentarium of therapy with refractory myeloma, I think that's still to be determined. And perhaps it's going to be occupying more of a niche role given the blossoming repertoire of highly efficacious immune-based agents, whether it's modified cellular therapy with CAR T a upcoming NK cell products that are being explored, and of course by specifically antibodies that have been robustly presented at this meeting demonstrating impressive responses. So, it's very conceivable that patients who were previously would be entertained for allogeneic SCT will now be in are treated with this kind of repertoire of novel immune agents. And so it may become a more of a niche role in patients who have exhausted all conventional or investigational approaches, but it does suggest that with this modified reduced intensity conditioning, treatment-related mortality can be lowered. With respect to the question at hand, it does not appear as though maintenance ixazomib helps these patients. And so observation alone following transplant versus an alternative maintenance strategy would be indicated. ASCO Daily News: OK. Well I'd like to ask you about the Apollo trial. That's Abstract 8046. This study looked at health-related quality of life of previously treated patients with multiple myeloma on a regimen of pomalidomide and dexamethasone plus subcutaneous daratumumab. Any surprises here, Dr. Gandhi? Dr. Mitul Gandhi: So, the Apollo study is a phase III trial primarily evaluating the efficacy of pomalidomide plus dexamethasone versus pomalidomide dexamethasone plus the incorporation of subcutaneous daratumumab in patients with myeloma who had received one prior line of therapy. And primary outcomes data had already been presented with improved rates of disease control with incorporation of daratumumab. With respect to this abstract, Dr. Terpos presented quality of life and patient-reported outcomes that was collected in parallel with the intervention arm of this study, and so they utilized the EORTC 30 item questionnaire to assess quality of life and subjective data from patients. And what they found was in the patients who had been on the DPD arm, or the daratumumab arm, there was a greater reduction in pain and no real augmentation or introduction of increased adverse events related to the additional agent. Moreover, there was no decline in physical or emotional functioning with DPD, but there was worsening decline in those elements compared to baseline for patients receiving pomalidomide and dexamethasone alone. There were higher rates of improvement with respect to control of disease symptoms, physical functioning, emotional functioning on the DPD arm. So, what does this tell us? Well in general, I think we've seen a plethora of agents that have improved outcomes with our patients with myeloma who are now living for years on therapy, increasingly and often even into a second decade. And so gaging the impact of therapy on quality of life, subjective sense of well-being is critical as these patients are going to be on therapy for quite a while. And so independent of serologic and laboratory response, we certainly want the interventions to improve functional capacity. And this data would suggest that you can achieve that in parallel with achieving better and deeper responses, which intuitively makes some sense, and they are often congruous. Involving the incorporation of an additional agent didn't worsen the sense of adverse events, but in fact improved the general sense of well-being. So this adds to the body of work of daratumumab on a MM dexamethasone backbone parting benefit without toxicity and also lending credence to the notion that by improving myeloma parameters, we're going to be in parallel improving quality of life. And so with the advent of all the other agents and novel compounds that are being developed after the acute toxicity period, we'd also expect to see improvement in quality of life as well. And so I think this was an important contributor to telling us this. ASCO Daily News: Excellent. Well thank you so much, Dr. Gandhi. I really appreciate your time today. Before we wrap up, any final thoughts from you on advances in multiple myeloma? There's certainly some really impactful work being done in the field. Dr. Mitul Gandhi: Yeah. I think I would encourage all the listeners to review the abstracts presented, particularly the oral abstracts as they get into some of the granularity on detail regarding the individual CAR T and bispecific antibody products, and very nicely demonstrate the durable responses that are being achieved in heavily pre-treated patients. Obviously kind of the next sort of hurdle in the field is to democratize these agents and make sure they're readily available for all patients. And there's a lot of work being done to ensure that management of the acute toxicity can be managed more broadly. So I think I'd pay particular attention to the oral abstract sessions which really demonstrate the novel agents that are being investigated. ASCO Daily News: Dr. Gandhi, thanks again for being on the podcast today to highlight some great new therapies in multiple myeloma. Dr. Mitul Gandhi: Thank you for having me. ASCO Daily News: And thank you 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. Mitul Gandhi: None disclosed.  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.

Silke Gillessen gives a safety update from this EORTC study focusing on fractures.

En este podcast, el Dr. Daniel Motola Kuba, oncólogo médico, adscrito al Hospital Médica Sur en la Ciudad de México, México, nos comenta algunos highlights del día 5 de ASCO 2021: Cáncer de próstata: · En cuestión de tamizaje temprano en hombres afroamericanos, se tomaron decisiones compartidas individualizadas mediante los datos de la infraestructura de administración de salud para veteranos. Cáncer de próstata metastásico sensible a la castración: · Se publicaron los primeros resultados del estudio fase lll, PEACE-1, en pacientes con cáncer de próstata metastásico sensible a la castración tratados con abiraterona + prednisona y/o radioterapia, demostrando una mejoría en supervivencia libre de progresión (SLP). · El estudio SWOG S1216, fase lll, comparó terapia antiandrogénica + TAK-700 + bicalutamida en pacientes recientemente diagnosticados con cáncer de próstata hormonosensible metastásico, mostrando una eficacia en supervivencia global y SLP. Cáncer de próstata resistente a la castración: · El estudio EORTC 1333/PEACE-3 demostró una disminución de la tasa de fracturas en los pacientes con cáncer de próstata resistente a la castración con radio-223 + enzalutamida vs. enzalutamida como monoterapia. Cáncer testicular: · Disminución en la supervivencia evaluando la tasa de mortalidad en pacientes con cáncer testicular que recibieron un tratamiento previo de cisplatino.

La Dra. Marinee Torres, oncólogo médico, adscrita al servicio de oncología del Cancun Cancer Institute, en Quintana Roo, nos habla brevemente sobre los highlights del día 3 del Congreso ASCO 2021: Cáncer de mama: Resultados de ECOG-ACRIN EA1131, un estudio posoperatorio, aleatorizado, fase III, de quimioterapia a base de platino vs. capecitabina en pacientes con cáncer de mama triple negativo residual, después de quimioterapia neoadyuvante. Resultados a más de 6 años de PALOMA-3, un análisis de supervivencia global de palbociclib más fulvestrant en pacientes con cáncer de mama avanzado, RH+/HER2- vs. fulvestrant solo. Resultados de SG actualizados a 5 años del estudio MONALEESA-3, de fulvestrant y ribociclib vs. fulvestrant solo en pacientes posmenopáusicas con cáncer de mama avanzado, RH+/HER2-. Resultados del estudio FUTURE-C-PLUS, prospectivo, fase II, de un solo brazo (famitinib en combinación con camrelizumab más nab-paclitaxel), para el tratamiento de pacientes con cáncer de mama triple negativo inmunomodulado avanzado, en primera línea. Melanoma: Resultados del crossover y rechallenge de la colaboración entre el EORTC 1325 y el KEYNOTE-054 de pembrolizumab en pacientes con melanoma en estadio lll de alto riesgo con resección completa. Los pacientes fueron aleatorizados a recibir pembrolizumab o placebo cada 3 semanas por un año y tras recurrencia, sin metástasis cerebrales, los pacientes con ECOG PS 0-2 fueron elegibles para ingresar a la parte 2 del estudio y recibir pembrolizumab durante máximo 2 años. Mieloma múltiple: Resultados actualizados del estudio KarMMa con idecabtagene vicleucel, una terapia CAR-T dirigida contra BCMA, para el tratamiento del mieloma múltiple en recaída o refractario.

Dr. Norah Henry, Breast Oncology Disease Lead at the University of Michigan’s Rogel Cancer Center, and chair of the 2021 ASCO Annual Meeting Scientific Program, highlights key abstracts and a host of dynamic sessions on equity and innovation in cancer research that will be featured during #ASCO21.   Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Nora Henry, who is the breast oncology disease lead at the University of Michigan's Rogel Cancer Center. She is chair of the 2021 ASCO Annual Meeting Scientific Program, and joins me to highlight key abstracts and a host of dynamic sessions that will be featured during the meeting. Dr. Henry reports no conflicts of interest relating to our discussion today and full disclosures relating to all episodes of the podcast are available at ASCO.org/podcasts. Dr. Henry, welcome to the ASCO Daily News podcast. Dr. Norah Henry: Hi, and thank you so much for inviting me. ASCO Daily News: Dr. Henry, I think everyone is curious to know what the hot topics will be at the Annual Meeting. So what are the disease sites that are showing tremendous progress this year? Dr. Norah Henry: Yeah, the last year has obviously been challenging because of the pandemic. That clearly hasn't stopped researchers around the world from continuing their exciting work and submitting their findings for presentation at the upcoming ASCO Annual Meeting. I strongly encourage everyone to attend the Plenary Session on Sunday, June 6, at which time we'll be highlighting practice-changing global research in breast cancer, nasopharyngeal cancer, cervical cancer, prostate cancer, and kidney cancer. In addition to what is being presented in the Plenary Session, please also be sure to check out the Oral Abstract Sessions, Clinical Science Symposia, Poster Discussion Sessions, and Poster Sessions for each of the tracks you're interested in, as well as the Highlights of the Day sessions. As you will see, there has been exciting progress across the spectrum of malignancies, especially with targeted therapies and immunotherapy. I have to say it's really difficult to narrow the abstracts down to just one or two key headlines. One study that comes to mind is an update of the EORTC 1325 KEYNOTE, 054 study by Dr. Eggermont and colleagues Abstract 9500. At the ASCO Annual Meeting they're reporting important findings about the use of pembrolizumab in patients with high risk stage III melanoma, who were initially treated with placebo, and who crossed over to pembrolizumab, or who were re-challenged with pembrolizumab after recurrence of disease. In hematologic malignancies, Dr. Byrd will present the results of the head-to-head comparison, a frontline acalabrutinib versus ibrutinib for CLL. That's Abstract 7500. And there's a third example, Dr. Wakeley will present Abstract 8500. The results of a phase III trial studying maintenance immunotherapy versus best supportive care in patients with stage II and III non-small cell lung cancer. These are just three examples of the tremendous progress that is being reported at this meeting from across the spectrum of oncology. In addition to these sessions I would also like to highlight the three special Clinical Science Symposia that are centered around the themes across multiple tracks. These are scheduled for live broadcast on Saturday, Sunday, and Monday with Q&A to follow. One session is about the use of artificial intelligence and machine learning in oncology, with a focus on its use in radiology and pathology (Artificial Intelligence: Optimizing Cancer Care Using Imagine and Pathology). This is a rapidly expanding area of interest and with potential implications for improving the care of patients around the world. The second session is about virally-induced cancers, including those screening and use of virus-related biomarkers for tailoring treatment (Virally Induced Cancers: Epidemiology and Biomarker-Guided Care). Finally, the third session is highlighting key studies that demonstrate how to implement research findings into clinical care with an emphasis on reducing disparities and opioid use in patients with cancer (Novel Initiatives to Address Disparities in Cancer).  Overall, the Scientific Program includes potentially practice-changing research findings from across oncology and hematology, including results of trials of novel therapies, studies examining tailoring of treatment based on biomarkers, and studies evaluating approaches to improve quality of life and reduce symptoms. We invite everyone to join us. ASCO Daily News: That sounds like a great variety of sessions and some incredible advances in cancer care. The theme of the Annual Meeting this year is equity. Can you tell us how this is incorporated into the Scientific Program? Dr. Norah Henry: Certainly. So this year's presidential theme is equity. Every patient, every day, everywhere. And this statement really underlies everything that we do and strive for. And therefore, we have tried to incorporate it throughout the Scientific Program. You'll see glimpses of it throughout the meeting, especially within the insightful presentations of the abstract discussions. And also, as I mentioned earlier, the special Clinical Science Symposia that will be broadcast on Saturday morning is focused on implementation science. And the abstracts selected for that session are related to disparities. Key work will be highlighted from a number of institutions that demonstrate how to successfully increase accrual of Black participants on clinical trials, how to reduce time to lung cancer surgery using an anti-racism intervention, and how to reduce unnecessary or inappropriate opioid use, both in the perioperative setting and also in patients with cancer more broadly. These investigators have done excellent work developing and implementing these interventions. And I encourage everyone to attend the session so they can get ideas for how to reduce disparities and improve equity at their own institutions. ASCO Daily News: Well, Dr. Henry this is our second virtual Annual Meeting. And there's no doubt that some aspects of the virtual format are here to stay as they enable more people across the globe to learn about new developments in cancer care. And it can spare others the time and cost of traveling to the meeting. When you think about the impact of the Covid-19 pandemic on how knowledge is shared within the oncology community, and the expanded use of telemedicine, for example, what are your thoughts on how the oncology community will emerge from the pandemic? Dr. Norah Henry: Thank you. And I find this to be a very difficult question, but obviously very timely. You know, I hope that this experience will have been an opportunity for us to grow as a community, and overall make changes for the better. Obviously, we were forced to make rapid changes last year as everything quickly became virtual. This year, however, we've had more time to plan and technology has advanced. And therefore, ASCO 2021 promises to be a very different experience compared to last year, with significantly more opportunities for interaction. Going forward, I think it'll be important to maintain some of these changes to the format. Having at least a portion of the meeting be virtual and interactive will allow more people from around the world, from oncologists to trainees to patients and patient advocates, to participate in the meeting in a meaningful way. Obviously, if you don't have to travel, there are upsides to that because it definitely allows more people to participate. But there are downsides as well in terms of decreased ability to have interactions as you meet (peers) in the hall, as we always do when we're in Chicago. But I think that with technological advances it'll be easier to do that going forward. Enabling more participation is truly a win for everyone. Also, from a patient care perspective, we now all have substantial experience with telehealth, whether we want it or not,  which is I think another positive that has come out of the pandemic. Using telemedicine, we are able to better follow up with our patients with less inconvenience, cost and hassle. This can certainly help improve access for patients. But we also need to ensure that better access is available across the board, and that patients who live in rural areas, for example, or who don't have a fast internet connection aren't left out from these improvements. So I think overall I'm very enthusiastic and hopeful that we can all learn from our experiences during the past year, and use this new knowledge to improve the care of our patients and the lives of both patients and providers alike. ASCO Daily News: Thank you Dr. Henry for that hopeful message, and for your efforts to put together a really robust and dynamic Scientific Program. Dr. Norah Henry: Thank you very much. And I really hope everyone thoroughly enjoys the meeting and is able to learn a lot about the new research advances that are ongoing, as well as take advantage of the excellent educational programming that will be going on simultaneously. ASCO Daily News: Absolutely. And thank you 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. Norah Henry Research Funding (Institution): Pfizer, Abbvie   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.

Mais um caso clínico! Dessa vez Iago e Vinicius falando dessa emergência oncológica importantíssima: Neutropenia Febril. Ouviu o caso? Faltou falar alguma coisa? Compartilha com a gente no @tadeclinicagem no instagram e no twitter! Minutagem (0:25) apresentação do convidado Dr. Vinicius (1:47) Início do caso (2:39) Exame físico (3:30) Resumo e primeiros comentários (8:40) Relevância do exame físico completo (10:12) Quanto a HPP (10:50) Seguimento do caso (11:55) O que pesquisar na anamnese (13:53) Quais exames solicitar (15:35) Atenção a sepse (17:10) Resultado dos exames (18:55) Neutropenia febril - conceitos (20:39) Voltando para história - outras hipóteses (22:20) Resumo do caso (23:10) Cuidados com o paciente com neutropenia febril (23:53) Score MASCC (28:12) Score CISNE (31:40) Fluxograma de internação (33:10) Outros critérios de alto risco (34:30) Aplicando os scores no caso clínico (37:06) Tratamento (38:50) Quando cobrir gram positivos resistentes (43:40) Continuação do caso (43:04) Comentários e condutas (51:13) Encerramento do caso (53:37) Resposta ao desafio anterior (54:26) Desafio da semana (55:00) Salves. REFERÊNCIAS. Taplitz, Randy A., et al. "Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update." J Clin Oncol 36.14 (2018): 1443-1453. Coyne, Christopher J., et al. "Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department." Annals of emergency medicine 69.6 (2017): 755-764. Aapro, M. S., et al. "2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours." European journal of cancer 47.1 (2011): 8-32. Rosa, Regis G., and Luciano Z. Goldani. "Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia." Antimicrobial agents and chemotherapy 58.7 (2014): 3799-3803. Braga, Catherine C., Randy A. Taplitz, and Christopher R. Flowers. "Clinical implications of febrile neutropenia guidelines in the Cancer patient population." Journal of oncology practice 15.1 (2019): 25. Klastersky, Jean, et al. "Management of febrile neutropaenia: ESMO clinical practice guidelines." Annals of Oncology 27 (2016): v111-v118. Zimmer, Andrea J., and Alison G. Freifeld. "Optimal management of neutropenic fever in patients with cancer." Journal of oncology practice 15.1 (2019): 19-24

Retiring ASCO Chief Medical Officer Dr. Richard L Schilsky gives a far-reaching interview with ASCO in Action podcast host ASCO CEO Dr. Clifford A. Hudis, who examines Dr. Schilsky’s trailblazing medical career, his leadership in ASCO and indelible mark on its research enterprise, and what he sees for the future of oncology. ASCO’s first-ever Chief Medical Officer even offers some friendly advice for Dr Julie Gralow, who starts as ASCO’s next CMO on February 15, 2021. In a touching tribute, Dr. Hudis also shares what Dr. Schilsky’s friendship and mentorship has meant to him personally, and suggests that Rich will still be supporting ASCO on critical priorities moving forward. Don’t miss this exchange with one of oncology’s greats! Transcript 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. CLIFFORD HUDIS: Welcome to this ASCO in Action podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. The ASCO in Action podcast is a series where we explore the policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Dr. Clifford Hudis. And I'm the CEO of ASCO and the host of the ASCO in Action podcast series. For today's podcast, I am especially pleased to have as my guest my friend, colleague, and mentor Dr. Richard Schilsky, ASCO's chief medical officer. Now, I am sure that many of our listeners have already heard that Dr. Schilsky will be leaving ASCO in February of 2021, retiring. However, I want to reassure everybody that even in retirement, he will continue to make contributions and provide leadership to all of us. And his illustrious and path-blazing career in oncology spanning more than four decades is not quite over thankfully. Rich is ASCO's first chief medical officer. And as such, he has made a truly indelible mark on all of us. He started with a proverbial blank piece of paper. The position had no precedent. It had no budget. It had no staff. But now after just eight years in the role, he has helped make the CMO a critically important position at the society. And I have to say that success is more than anything due to Rich's vision and his leadership. And that's some of what we'll be talking about today. So Rich, thank you very much for joining me today for what I hope is going to be a great casual but informative conversation about your amazing career, your unique role at ASCO, and maybe most importantly in the end what you see for the future of oncology not just in the United States, but around the world. Thanks for coming on, Rich. RICHARD SCHILSKY: Thanks, Cliff. It's great to be here today. CLIFFORD HUDIS: So with that, let's just dive right in and start at the very beginning. Rich, tell everybody why you decided to become an oncologist and maybe share a little bit about what those early days looked like for you and, in that context, what it was like to have cancer at the beginning of your career. RICHARD SCHILSKY: Well, I knew from an early age that I wanted to be a doctor. And in fact, I had written a little essay when I was in sixth grade as a homework assignment called My Ambition. And my mother had tucked that away in a scrapbook. And I found it a number of years ago. And on rereading it, it was quite amazing to me to see what I was thinking about even then. Because I said not only did I want to be a doctor, but I didn't think that was enough, that I wanted to be a medical researcher because I wanted to discover new information that would help people heal from whatever their diseases might be. And so it was never really any doubt in my mind that I would be a physician. I went to medical school at the University of Chicago. But I was living in New York City at the time having grown up in Manhattan. And the only year we had off in medical school, the only time we had off in medical school, was the summer between the end of the first year and the beginning of the second year. So during that time, I went back to Manhattan. And I was able to get a fellowship from the American College of Radiology that allowed me to essentially hang out in the radiation therapy department at New York University Medical Center, which was within walking distance of where I grew up. And so I would go over there every day. And I was taken under the wing of a young radiation oncologist. And of course, I wasn't really qualified to do anything at that point except to follow him around, talk and listen to the patients. But that turned out to be a really formative experience for me because we saw the whole gamut of cancer. We saw head and neck cancers. We saw lung cancer. We saw patients with breast cancer and prostate cancer. And in those years-- this is the early 1970s-- many of these patients have fairly locally far advanced disease and were quite debilitated by it. But listening to their stories, hearing about their hopes and their struggles, really demonstrated to me the human side of cancer. So I went back to school and thought about this in the context of my own personal experience, which dated back to when I was in college when my mother's mother, my maternal grandmother, was diagnosed with breast cancer. This was 1968. And as you well know, there were very few therapies available for breast cancer in the late 1960s, mostly hormone therapies. And my grandmother had the treatment that was considered standard of care at that time, which was extended radical mastectomy followed by chest wall radiation. And some years after that first mastectomy, she had a breast cancer that developed in the opposite breast and had a second extended radical mastectomy and chest wall radiation. And these were very traumatic and disfiguring procedures for her to go through. Anyway, long story short is after another few years, she developed bone metastases and then brain metastases. And there was really very little that could be done for her other than hormone therapies. And having observed her go through that illness and realizing how limited our treatment options were and then having the experience after my first year in medical school pretty well cemented for me that I wanted to be an oncologist. I thought actually about being a radiation oncologist. But then I did my internal medicine rotation in medical school, fell in love with internal medicine. And that sort of put me on the path to be a medical oncologist. The clinical challenge of caring for cancer patients, the emotional attachment to those patients, and, of course, even then, the unfolding biology of cancer was so intellectually captivating that I actually applied for oncology fellowship when I was a senior medical student. So even before going off to do my medical residency, I had already been accepted as a clinical associate at the National Cancer Institute to start two years hence. And that's how I became an oncologist. CLIFFORD HUDIS: So it's so interesting. Because, of course, the story I'm sure for many people interested not just in oncology, but even medical education, there are little things that don't happen nowadays that happened with you like that last little vignette about the early acceptance into an advanced training program before your fellowship among other things. Can you remind us about the timeline? Because I think one of the things that many of our listeners often can lose sight of is just how new oncology really is as a specialty. ASCO itself founded in 1964. And the first medical oncology boards were mid-'70s, right? So you were in med school just before that second landmark, right? RICHARD SCHILSKY: That's right. I graduated from medical school in 1975. I started my oncology fellowship in 1977. And I got board-certified in medical oncology and joined ASCO in 1980. And so that was the time frame at that point. CLIFFORD HUDIS: So the internal medicine was actually, if I heard you right, just two years, not the now traditional four. RICHARD SCHILSKY: Yeah. I was a short tracker. I did only two years of internal medicine training rather than three. I did my training at Parkland Hospital and University of Texas Southwestern in Dallas with at that time a legendary chair of medicine, Don Seldin, who I had to get permission from him to leave the program prior to completing the third year of residency because I had already been accepted into fellowship at NCI. And he, Seldin, who was a brilliant chairman and a brilliant nephrologist, was not at all interested in cancer. And it took a bit of-- I was going to say arm twisting, but it really took bleeding on my part to get him to agree to allow me to leave the residency program to go to the NCI. But he eventually agreed. And in those years, the first-year clinical fellowship at the NCI was like being an intern all over again. There were about 15 of us. We were on call overnight in the clinical center once every two weeks. We cared for all of our inpatients as well as had a cadre of outpatients. We did all of our own procedures. We had no intensive care unit. So patients who were sick enough to require ventilator support, we cared on the floor in the inpatient service on our own with guidance from senior oncologists. It was a bit different from the way it is now. But, of course, it was fantastic on-the-job training because we just learned a ton and had to learn it very quickly. CLIFFORD HUDIS: So that's actually a great segue to the advances because there was a lot to learn then. But, wow, there's a lot more to learn, I think, now. And I have real sympathy for trainees and younger oncologists for the breadth of what they need to learn. Again, just testing your memory, but platinum came along pretty much in the mid-'70s as well, right? That was a pivotal expansion of the armamentarium for us. So what do you see-- when you summarize progress in cancer research and care over these decades, what do you think are the most pivotal or revolutionary milestones that you identify over the span of your career? RICHARD SCHILSKY: Yeah. It's really interesting to think about it historically. There were the early years of discovery in oncology from the 1950s to the 1970s when we really had the introduction of the first chemotherapy drugs and the miraculous observation that people with advanced cancer could actually obtain a remission and, in some cases, a complete remission with chemotherapy and combination chemotherapy in particular. And so that was the formative years of oncology as a medical specialty and really proof of concept that cancer could be controlled with drugs. When we got into the 1980s, the 1980s in many respects were the doldrums of progress in clinical oncology. There really was not a lot of innovation in the clinic. But what was happening and what was invisible to many of us, of course, was that was the decade of discovery of the fundamental biology of cancer. That's when oncogenes were discovered, when tumor suppressor genes were discovered, when it became clear that cancer was really a genetic disease. And that is what transformed the field and put us on the path to targeted therapy and precision medicine as we think of it today. So I think that clearly understanding the biology of cancer as we do now and all that it took to lead us to that point, which was a combination of understanding biology, developing appropriate technology that would, for example, enable the sequencing of the human genome and then the cancer genome. And the other formative technology in my opinion that really changed the way we care for cancer patients was the introduction of CT scanning. When I was still a fellow at the NCI, we did not have a CT scanner. If we needed to get detailed imaging of a patient, we did tomography. And if you remember what tomograms looked like, they were really blurry images that you could get some depth perception about what was going on in the patient's chest or abdomen. But they really weren't very precise. When CT scanning came along, it really revolutionized our ability to evaluate patients, assess the extent of disease, stage them in a much more precise way, which then allowed for better patient selection for curative surgery, better radiation therapy planning. So we don't often point to imaging advances as some of the transformative things that paved the way in oncology, but I think imaging is really overlooked to some extent. So I think the technology advances, the biological advances, are the things that really allowed the field to move forward very quickly. And by the time we got into the mid-1990s, we were beginning to see the introduction of the targeted therapies that have now become commonplace today. And then it was around 2000, I think, that we saw the introduction of Gleevec. And I'm reminded always about an editorial written by Dan Longo in The New England Journal a few years ago. And Dan and I were fellows together. We worked side by side on the wards at the clinical center and became very good friends. And Dan in his role as a deputy editor of The New England Journal wrote an editorial a few years ago that was titled "Gleevec Changed Everything." And Gleevec did change everything. It changed our entire perception of what were the drivers of cancer and how we might be able to control cancer very effectively and potentially put it into long-term remission. Now, of course, we know now that the whole Gleevec story is more of an exception than a rule in targeted therapy. And, of course, we know that tumors become resistant to targeted therapies. But we couldn't have known any of this back in the early years of oncology because we had no real insight into what caused cancer to grow or progress. And the notion of drug resistance, while we realized that it occurred, we had no idea what the mechanisms were. So it's such a different landscape now than what it used to be. It's quite remarkable. CLIFFORD HUDIS: So as you tell the story, there's, of course, a lot of focus on technology, whether it's biology and understanding the key features of malignancy or imaging or more. But what I also note in your story and I want to come back to is the people. And I can't help but reflect on where we are in this moment of the COVID-19 pandemic. Yes, we've moved to telemedicine. Everything can be accomplished via technology. And, yet, the human touch is so important. When we think about being in the room with people, when we think about face to face from the context of career development and your own career, you touched on Dr. Seldin, I think, already from the perspective of internal medicine training. But are there are other mentors or important shapers of your career that you think we should know about? RICHARD SCHILSKY: Well, probably, the most influential person early in my career in medical school was John Altman. John, you may know, was the inaugural director of the University of Chicago's NCI-designated Cancer Center, which was one of the very first NCI-designated cancer centers in 1973 after the National Cancer Act of 1971 created the cancer centers program. And John, who was a leading oncologist studying Hodgkin and non-Hodgkin's lymphoma, was a faculty member there. He was the director of our cancer center as I said. He took me under his wing even when I was in medical school and served as a real role model and mentor to me. When I was in my internal medicine training as I mentioned earlier, Don Seldin, the chair of medicine, was never particularly interested in oncology. So, to some extent, I didn't have-- I had great internal medicine training. But I did not have good mentorship in oncology. When I got to the NCI, then my whole world really opened up. And the two pivotal people there in my career were Bob Young, who was chief of the medicine branch and was my clinical mentor and remains a mentor and friend to this day, and then, of course, Bruce Chabner, who was the chief of the clinical pharmacology branch. And in my second year of fellowship when we all went into the laboratory, I went into Bruce's lab. And that's where I really got interested in the mechanism of action of anti-cancer drugs and ultimately in drug development and early phase clinical trials. And both Bob and Bruce remain very close to me even today. CLIFFORD HUDIS: So I'm concerned about time on our call today on our discussion. Because we could obviously fill lots of hours on all of these remarkable experiences and amazing people you worked with. But I'm going to ask that we fast forward a little bit. You and I share, I think, passion and love for ASCO. So I think that it's reasonable for us to focus a little bit on that for the time we have left here. You didn't start out obviously as chief medical officer at ASCO. But you were a really active ASCO volunteer and leader. Maybe tell us a little bit about some of the ASCO volunteer roles that you engaged in and what that meant to you at the time and how that led to this role. RICHARD SCHILSKY: Well, I'll be brief. I joined ASCO in 1980 at the first moment that I was eligible to join ASCO. I had attended my first ASCO meeting the year before, 1979, when I was still in my fellowship training. And it was clear to me even then when the whole annual meeting was about 2,500 people in two ballrooms in a hotel in New Orleans that that was a community of scholars and physicians that I wanted to be a part of. And so, over the years, I did what people do even today. I volunteered to participate in whatever ASCO activity I could get involved with. Over the years-- I think I counted it up not too long ago-- I think I served or chaired 10 different ASCO committees, more often serving as a member, but in a number of those committees also serving as the chair over many years. And as I became more deeply involved in ASCO and saw other opportunities to engage, I had the opportunity to run for election to the board and was-- after a couple of tries was elected to serve on the board and then eventually elected to serve as ASCO president in 2008-2009. But the attraction of ASCO in many ways was a community of diverse but, in many ways, like-minded people, people who had similar passion and drive and focus. But I think what you get at ASCO in many ways is the wonderful diversity of our field. If you work in a single institution for much of your career as I did and as you did, you get to know that institution pretty well. You get to know its perspectives and its biases and its strengths and its weaknesses. But there's a whole world of oncology out there. And you can get exposed to that at ASCO because you meet and work with colleagues from every clinical setting, every research setting, people who have remarkable skills and interests and passions. And it's just a wonderful environment to help develop your career. So I consider myself to be extremely fortunate to have had the journey in ASCO that I've had culminating, of course, with ultimately my coming on the staff as ASCO's first chief medical officer. CLIFFORD HUDIS: We often joke about that blank sheet of paper. But in retrospect, it's very obvious that you had built up that collection of LEGO blocks, and then you assembled them all into the ASCO Research Enterprise, a name you gave it. And it really, in retrospect, builds, I think, very cleanly upon all of your prior experience, but also the vision that you developed based on that experience for how research should be conducted. Can you maybe share with everybody the scope and vision for the ASCO Research Enterprise, what the intent was, and where you see it going, and what it includes today? RICHARD SCHILSKY: Sure. I won't claim that I came to ASCO with the whole thing fully developed in my mind. As you said, when I came, I literally did have a blank slate. Allen Lichter, who hired me, said, come on board and help me make ASCO better. And so I, in a sense, reverted to what I knew best how to do, which was clinical research. And having in my career been a cancer center director, a hem-onc division chief, a cooperative group chair, I had a lot of experience to draw on. And it was obvious to me that ASCO was fundamentally an organization that took in information from various sources, evaluated it, vetted it, collated it, and then disseminated it through our various channels, most notably our meetings and our journals. But ASCO itself did not contribute to the research enterprise. And that seemed to me to be a lost opportunity. We knew that ASCO had lots of data assets that could be of interest to our members and to the broader cancer community. But they were scattered all around the organization and not particularly well annotated or organized. So we began to collate those. And they are now available to ASCO members on the ASCO data library. I recognized that we did not have an organized unit in ASCO to support or facilitate or conduct research. So, in 2017, we formed the Center for Research and Analytics and brought together staff who were already working at ASCO but scattered in different departments but all people who had an interest in clinical research or research policy and brought them into this new unit, which has really become the focal point for research work at ASCO. We recognized that ASCO members for many years were interested in surveying their colleagues, surveying other ASCO members, to help advance research questions. But ASCO actually had a policy that prohibited that. So that never really made good sense to me. It seemed like a lost opportunity. And we were able to create a program and have the ASCO board approve it whereby any ASCO member could opt in to participate in what we now call the Research Survey Pool. And in doing so, they are essentially agreeing to participate in research surveys conducted by their colleagues. So that program is now up and running. There are, I think, eight surveys that have been completed or are currently in the field. And this is now a service that ASCO provides through CENTRA to its members to enable them to survey their colleagues for research purposes. Most importantly, I think we saw an opportunity back in 2014 or 2015 to begin to learn from what our colleagues were doing in clinical practice as they began to deploy precision medicine. And there was a lot of genomic profiling that was going on at that time. It was revealing actionable alterations in roughly 30% or so of the tumors that were profiled. But there was a lot of difficulty in doctors and patients obtaining the drugs that were thought to be appropriate to treat the cancer at that particular time because most of those drugs would have to be prescribed off label. And there was not a sufficient evidence base to get them reimbursed. And, moreover, even if they could be reimbursed, there was no organized way to collect the patient outcomes and learn from their experiences. So that led to us developing ASCO's first prospective clinical trial, TAPUR, which really solves both of those problems. Through the participation of the eight pharmaceutical companies that are engaged with us in the study, we are providing-- at one point, it was up to 19 different treatments free of charge to patients. These are all marketed drugs but used outside of their FDA-approved indications. And we were collecting data on the patients, the genomic profile of cancer, the treatment they received, and their outcomes in a highly organized way. And so now this is a study that we launched in 2016. We're now almost to 2021. We have more than 3,000 patients who have been registered on the study, meaning consented to participate, more than 2,000 who have been treated on the study. And we are churning out results as quickly as we can about which drugs are used or not useful in the off-label setting for patients whose tumors have a specific genomic profile. So we built all this infrastructure. And having this in place has also then allowed us to respond rapidly to unmet needs. So when the COVID-19 pandemic overwhelmed all of us, and when our members were looking for information about what was the impact of COVID-19 on their patients, one of the things we were able to do because we had CENTRA, because we had a skilled staff and an infrastructure, was to very quickly stand up the ASCO COVID-19 registry, which we launched in April of this year. And there are now about 1,000 patients who've enrolled in the registry from around 60 practices that are participating. And we will follow these patients now longitudinally and learn from their experiences what has been the impact of the COVID-19 illness on them and their outcomes, how has it disrupted their cancer care, and ultimately how that impacts their overall cancer treatment outcomes. So as I now contemplate leaving ASCO after eight years having started with a blank slate, I'm very proud of the fact that I think I'm leaving us with a remarkable infrastructure. We now have a clinical trials network of 124 sites around the country participating in TAPUR that we never had before. We have through the work of CancerLinQ a real-world evidence data generator that is beginning to churn out valuable insights. We have a capacity to survey ASCO members for research purposes. We have an ability to stand up prospective observational registries to gather information longitudinally about patients and their outcomes. We have a core facility in CENTRA with highly skilled data analysts and statisticians that can support these various research activities. So ASCO is now primed, I think, to really contribute in a very meaningful way to the gaps in knowledge that will forever exist in oncology just because of the complexity of all the diseases we call cancer. And that's what I mean by the ASCO Research Enterprise. It is in fact remarkable and, I think, powerful enterprise if we continue to use it effectively. CLIFFORD HUDIS: Well, that's an interesting segue to my next thought, which is really about what comes next. I'll talk about you. But let's start with ASCO first. Your successor, Dr. Julie Gralow, obviously has been announced publicly. She's an accomplished clinician and researcher. She has a known recognized passion for patients, patient advocacy, clinical research through her leadership at SWOG but also health care equity and global oncology. So from your perspective, having created all of these assets and resources, what advice would you give Dr. Gralow publicly on how to make the position hers, what to take us to next? And I do want to acknowledge for everybody listening that the hints I've been making up until now are that Rich has agreed that he will continue to contribute as a leader to TAPUR for the short term, at least, at least the next year helping Julie get fully oriented to this program and others. So what will your advice be to Julie? RICHARD SCHILSKY: That's a great question. She's a great selection. And congratulations on hiring her. I think there are two key issues, I think, maybe three. One is to have a broad scope and cast a wide net. Oncology care and cancer research and cancer biology are incredibly complicated and nuanced and broad in scope. And although Julie is an accomplished breast cancer clinician and researcher, in this role at ASCO, you have to be very broad. You have to understand all of cancer care, all of cancer research, all of policy and advocacy not as an expert in necessarily in any one aspect of ASCO's work, but you have to understand the impact of all of those things on cancer care providers and on cancer patients. And it's important to always be looking to the future. The future is going to be here before you know it. And we as a professional society have to prepare our members for that future. So that leads me to the second point, which is listen to the members. The members are the people on the front lines who are delivering care to patients every day. And, fundamentally, ASCO's job is to be sure that our members have all the tools and knowledge and resources that they need to deliver the highest quality care to patients every day. So listening to what they need, what their struggles are, what their burdens are, is extremely important. And then the third thing I would recommend to her is that she get to know the staff and colleagues that she'll be working with. ASCO has a remarkably accomplished, skilled, motivated, passionate staff, many of whom have been with the organization for years, if not decades, who understand what ASCO can and cannot do and who understand what our members need. And she will be well advised to spend a good portion of her first few months on the job just listening and learning from her colleagues. CLIFFORD HUDIS: That's always good advice for anybody making a big career move. But, of course, the wisdom you bring to it is palpable and much appreciated. And I'm sure Julie will be taking your advice. And, by the way, so will I continue to do that even after you make your move. So speaking of your retirement, can you share with us a little bit about what it's actually going to look like for you? Is it about family? Or are you still going to have some professional engagement? Again, I suggest that there might be some already, but maybe you could expand on it. RICHARD SCHILSKY: Yeah. I'm still fully focused on my work at ASCO. And, of course, as you know, when I wake up on February 15, I will no longer be ASCO's chief medical officer. And it's going to be a bit of a rude awakening. Fortunately, I will be able to continue my engagement with ASCO through the TAPUR study as you mentioned. I will, of course, forever be at ASCO member and a donor to Conquer Cancer and be willing to serve the society in any way. I have a number of activities that I've been involved with even throughout my time at ASCO. Not-for-profit boards, for example-- I'm on the board of directors of Friends of Cancer Research. I'm on the board of directors for the Reagan-Udall Foundation for FDA. I plan to continue with those activities as long as they'll have me. I've been serving the last few years on the board also of the EORTC, the large European cooperative clinical research group. And I expect to continue in that role. Beyond that, I will see what opportunities come my way. I think one of the things about retirement if you will that I'm looking forward to is the opportunity to pick and choose what to work on based on what interests me without having the burdens of having a full-time job. On the personal front, of course, we're all looking forward to crawling out from the pandemic. I've basically been locked in my home outside Chicago since March. And I'm looking forward to getting back out to a little bit of a social life. As you know, I have two grown daughters and now three grandchildren, two of whom are in Atlanta, one of whom is near by us in the Chicago area. So looking forward to spending time with them as well. So it will be a change for me to be sure after working as hard as-- I feel like I've worked for really now 45 years since I graduated from medical school. But I also feel like I'm not quite done yet and that I still have ways in which I can contribute. I just feel like at this point, maybe it's time for me to choose how I want to make those contributions and spend a little bit more time doing some other things. CLIFFORD HUDIS: Well, both you and my predecessor, Allen Lichter, are modeling something, have modeled something, that I think is not often discussed but can be very important. For people and for institutions, change is not a bad thing. And setting the expectation that you will pour your heart and soul into something but not necessarily do it alone or forever and not prevent others from taking that role at some point, that's a really-- I think it's a selfless kind of sacrifice in a way. Because, of course, you could stay and do what you're doing for longer. But as you and I have discussed, there is a value for all of us collectively in having fresh eyes and new people take organizations in a new direction. That's how I ended up here frankly. And I think that's the kind of opportunity you're creating right now, something that should be celebrated in my opinion. RICHARD SCHILSKY: Well, thanks. And I couldn't agree more. When I look back at the arc of my career and having all the different kinds of leadership roles that I've had, I basically have made a job change every 8 to 10 years. I was the director of our cancer center for nearly 10 years. I was associate dean for clinical research at the University of Chicago for eight years, another position that I created from a blank slate at that institution. The exception was serving 15 years as a CALGB group chair. But that was a position I really loved and enjoyed and felt like at the end of the first 10 I hadn't quite accomplished everything I wanted to accomplish. But the point is that I think it is both necessary for organizations to have regular leadership change. And it's also refreshing for us as individuals. There gets to a point where you feel like you can do your job in your sleep. And I actually think that's a good time to make a change. Because if that's the way you feel, you're not being sufficiently challenged. And you're probably not being sufficiently creative. And so it's a good time to move on and refresh your own activities and give your organization a chance to bring in someone to hopefully build on whatever you've created and bring it to the next level. CLIFFORD HUDIS: Well, I agree with all that, although I think your comment there about doing the job in your sleep would not apply because I'm pretty confident that the environment and opportunities have continued to evolve in a way that has made it interesting from beginning to end. But you don't have to rebut me on that. I just want to thank you very, very much, Rich. As we set up this podcast, I expected that we would have a really fun and enlightening conversation. And, of course, you did not disappoint. We could talk for much, much longer if we only had the time. On a personal note to you and for the benefit of our listeners, I want to share that Rich has been for me a remarkable friend and mentor and colleague. I first met Rich at the very beginning of my career when my mentor, Larry Norton, pushed me out from Memorial into the larger world. And he did that first and primarily through ASCO and the Cancer and Leukemia Group. Those are really the two places where I was exposed to the world. And through the CALGB, Rich really began to offer me and others, many others, opportunities that shaped careers plural, mine and others. So when I got to ASCO as CEO, Rich was there. And I knew I could always depend on you to be clearheaded, intellectually precise, constructive, visionary. And the thing about you, Rich, is that you never would say yes to anything unless you knew for sure you could do it and indeed, I think, how you could do it. I always share this story which your staff at CENTRA pointed out to me. And I have to admit that I hadn't picked it up myself. But in all the years of now working down the hall from Rich, probably hundreds and hundreds of hours of meetings, he never has taken a note in front of me. And, yet, everything we talk about, every action item we conclude to pursue, they all get done. So I don't know, Rich. You have a remarkable way of organizing your thoughts and your plans, keeping it together, and getting things done. And I'm going to miss that tremendously in the years ahead. So, Rich, I want to say congratulations. Congratulations on reaching this really important milestone in your life. Thank you on behalf of ASCO and the broader oncology community and the patients we care for and their families for making the world a better place. And just as a small thing, thank you for joining me today for this ASCO in Action podcast. RICHARD SCHILSKY: Thank you, Cliff. It's been great. CLIFFORD HUDIS: And, for all of you, if you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. And, while you're there, be sure to subscribe so you never miss an episode. The ASCO in Action podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. Until next time, thank you for listening to this ASCO in Action podcast.

The recently published EORTC 62092 trial (STRASS) examines abdominal recurrence in patients after surgical resection of retroperitoneal sarcomas.  This randomized study compared these recurrences in patients receiving neoadjuvant radiation versus those undergoing surgery alone.  Rebecca Gladdy MD, PhD and Ashleigh Guadagnolo, MD join moderator and SSO Sarcoma Disease Site Work Group Chair, Aimee Crago, MD, PhD, to provide insight and analysis from both surgical and radiation oncology perspectives, discussing how this practice-changing trial is altering the approach to patients with these diseases. 

Ao contrário dos sarcomas de extremidade, a eficácia da radioterapia nos casos de sarcoma retroperitoneal ainda não está estabelecida. Com o objetivo de avaliar o impacto da radioterapia pré-operatória associada à cirurgia versus cirurgia isolada na sobrevida livre de recorrência abdominal, o STRASS Trial foi idealizado. .....Também conhecido como EORTC-62092, este estudo incluiu 31 instituições localizadas em 13 países da Europa e América do Norte. Incluindo apenas pacientes com idade ≥18 anos portadores de sarcoma retroperitoneal primário localizado e passíveis de ressecção, este estudo teve resultado negativo e não rejeitando a hipótese nula, com sobrevida livre de recorrência abdominal mediana de 4,5 anos no grupo de radioterapia + cirurgia e 5,0 anos no grupo apenas de cirurgia (p = 0,95)......Os autores concluíram então que “A radioterapia pré-operatória não deve ser considerada como tratamento padrão para o sarcoma retroperitoneal.”.....No entanto os Drs. Ranyell Spencer e Elton Leite discutiram esse paper e discordaram dessa conclusão diante de vieses sistemáticos do estudo......Sejam bem-vindos a mais um episódio do Clinical Papers Podcast!.....Não perca esta discussão e saiba mais sobre o paper pelo link: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30446-0/fulltext

Dr Paul Sargos : Radiothérapie postopératoire des cancers de la prostateQuel est le rationnel et l’historique de la radiothérapie postopératoire dans le cancer de prostate ? Quels sont les résultats marquants du GETG AFU 17 récemment publié dans Lancet Oncology ? Comment ces résultats s’intègrent-ils par rapport aux essai RADICALS, RAVES et la récente méta-analyse ?Le Dr Paul Sargos (Cancérologue radiothérapeute de l’institut Bergonie, Centre Régional de lutte contre le Cancer, Bordeaux) répond à toutes vos questions !L’orateur n’a pas reçu de rémunération pour la réalisation de cet épisode.Pour aller plus loin :Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol. 2009;181(3):956-962. doi:10.1016/j.juro.2008.11.032Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, van Velthoven R, Maréchal JM, Scalliet P, Haustermans K, Piérart M; European Organization for Research and Treatment of Cancer. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet. 2005 Aug 13-19;366(9485):572-8. doi: 10.1016/S0140-6736(05)67101-2. PMID: 16099293.Wiegel T, Bartkowiak D, Bottke D, Bronner C, Steiner U, Siegmann A, Golz R, Störkel S, Willich N, Semjonow A, Stöckle M, Rübe C, Rebmann U, Kälble T, Feldmann HJ, Wirth M, Hofmann R, Engenhart-Cabillic R, Hinke A, Hinkelbein W, Miller K. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. Eur Urol. 2014 Aug;66(2):243-50. doi: 10.1016/j.eururo.2014.03.011. Epub 2014 Mar 21. PMID: 24680359.Sargos P, Chabaud S, Latorzeff I, Magné N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulié M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1341-1352. doi: 10.1016/S1470-2045(20)30454-X. PMID: 33002438.Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, Williams SG, Brown C, Delprado W, Haworth A, Joseph DJ, Martin JM, Matthews JHL, Millar JL, Sidhom M, Spry N, Tang CI, Turner S, Wiltshire KL, Woo HH, Davis ID, Lim TS, Pearse M. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020 Oct;21(10):1331-1340. doi: 10.1016/S1470-2045(20)30456-3. PMID: 33002437.Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, Parmar MKB, Tierney JF; ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020 Sep 28:S0140-6736(20)31952-8. doi: 10.1016/S0140-6736(20)31952-8. Epub ahead of print. PMID: 33002431.Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O'Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Røder MA, Sayers I, Simms M, Wilson J... See acast.com/privacy for privacy and opt-out information.

A lot can happen in two years. You might have matched into residency, graduated from fellowship, had a kid... Or several phase II trials in low grade glioma research could have been published. Since the original airing of this episode in May 2018, there have been a few updates in neuro-oncology. We'll cover some of the major ones this week in the BrainWaves podcast. Produced by James E. Siegler, Brian Nahed and Jorg Dietrich. Music courtesy of Ian Sutherland, Lovira, and Lee Roosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast. REFERENCES McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, Olivi A, Brem H and Quinones-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008;63:700-7; author reply 707-8. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR and Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:3065-70. Schiff D. Low-grade Gliomas. Continuum (Minneap Minn). 2017;23:1564-1579. Wen PY and Huse JT. 2016 World Health Organization Classification of Central Nervous System Tumors. Continuum (Minneap Minn). 2017;23:1531-1547. Bell EH, Zhang P, Fisher BJ, Macdonald DR, McElroy JP, Lesser GJ, Fleming J, Chakraborty AR, Liu Z, Becker AP, Fabian D, Aldape KD, Ashby LS, Werner-Wasik M, Walker EM, Bahary JP, Kwok Y, Yu HM, Laack NN, Schultz CJ, Gray HJ, Robins HI, Mehta MP and Chakravarti A. Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol. 2018;4:1405-1409. van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, de Vos FYF, Wick A, Mulholland PJ, Taphoorn MJB, Lewis J, Weller M, Chinot OL, Kros JM, de Heer I, Verschuere T, Coens C, Golfinopoulos V, Gorlia T and Idbaih A. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018;19:1170-1179. Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ and Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20:1011-1022. Bell EH, Zhang P, Shaw EG, Buckner JC, Barger GR, Bullard DE, Mehta MP, Gilbert MR, Brown PD, Stelzer KJ, McElroy JP, Fleming JL, Timmers CD, Becker AP, Salavaggione AL, Liu Z, Aldape K, Brachman DG, Gertler SZ, Murtha AD, Schultz CJ, Johnson D, Laack NN, Hunter GK, Crocker IR, Won M and Chakravarti A. Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020:JCO1902983. Breen WG, Anderson SK, Carrero XW, Brown PD, Ballman KV, O'Neill BP, Curran WJ, Abrams RA, Laack NN, Levitt R, Galanis E, Buckner JC and Shaw EG. Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma. Neuro Oncol. 2020;22:830-837. Ullrich NJ, Prabhu SP, Reddy AT, Fisher MJ, Packer R, Goldman S, Robison NJ, Gutmann DH, Viskochil DH, Allen JC, Korf B, Cantor A, Cutter G, Thomas C, Perentesis JP, Mizuno T, Vinks AA, Manley PE, Chi SN, Kieran MW and Consortium NFCT. A Phase II Study of Continuous Oral mTOR Inhibitor Everolimus for Recurrent, Radiographic-Progressive Neurofibromatosis Type 1-Associated Pediatric Low-Grade Glioma: A Neurofibromatosis Clinical Trials Consortium Study. Neuro Oncol. 2020.

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. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Manish Shah from New York Presbyterian Weill Cornell Medical Center, senior author on "Treatment of Patients with Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Shah. Thank you, it's a pleasure and honor to be here. So first, can you give us a general overview of what this guideline covers? Yes, absolutely. So the "Treatment of Patients with Early-Stage Colorectal Cancer" is a resource-stratified guideline. And it focuses on the management of patients with early-stage colon cancer. It's different than the surveillance and screening guideline that was written simultaneously for ASCO as another resource-stratified guideline. We felt that this was a big enough topic that we should keep it separate. So it really talks about the management of pre-malignant lesions, as well as early-stage colon cancers, as well as rectal cancers. And the other aspect of this is that we really focused on how the guideline may apply in settings where there-- they don't have maximal resources, so basic or limited settings as well. So I would like to talk a little bit about how the guideline was created, because I think that's an important aspect. And it distinguishes it from typical other ASCO Guidelines. So the management of colon cancer or colorectal cancer, there's a lot of literature on this. And there are several guidelines that have been produced by colorectal cancer societies, or surgical societies, or from other countries like the EORTC, or Japan, or Korea, or even the UK. So in fact, there were, I think, 30 to 40 different guidelines that we reviewed. And we felt that, instead of doing a new literature search to kind of rehash much of the same information, we reviewed all the guidelines for certain quality measures to then select a handful of guidelines that we would use as the reference for each of our key questions or key points. And this was done in a formal process, the first by ASCO and Sarah, who was the ASCO staff who wrote the guideline, along with the members of the guideline panel. And in this process, I think that we have a pretty comprehensive guideline that covers the questions with the best evidence available. So what are the key recommendations of this guideline? Yeah, so we addressed some several questions with regard to key recommendations. The first question, for example, was, what's the optimal treatment for patients with colon cancer that would be clinical stage 1 through 3c? And we distinguish that from a non-obstructing cancer to obstructing cancers as well, because the management would be very different. And what we really sort of focused on is that these patients should have resection following oncologic principles. Then ideally, they should have an en bloc resection by a surgical oncologist to give the patients the best chance of care. But I think what's unique to resource-stratified guidelines, and what we have to do is sort of highlight the care that would be achieved in settings that have less resources. So a non-obstructing colon cancer in a basic setting should still have surgery and should still undergo an en bloc resection following standard oncologic principles. So that was, for example, one of the key points that was uniform across all the settings. Other things were how to manage [INAUDIBLE] colon cancer. So in more enhanced and maximal settings, sometimes there might be opportunity to place a colonic stent, for example, by either a colorectal surgeon or by someone who has specialized training in the placement of these stents. And that would be a preferred approach in both the enhanced and maximal guidelines, whereas in a more basic setting, the recommendation was to perform a resection and possibly, if required, if a resection was not possible, a diversion to overcome the obstruction in that localized setting. There were other recommendations that were also important. So for example, in early-stage rectal cancer, so clinical stage 1, T1 and 0 rectal cancer, in a maximal setting, these are sort of low-risk cancers without adverse features like high-grade or involvement of lymphovascular structures. The surgical oncologist and/or colorectal surgeon might consider a local excision such as the TEM procedure, which is a transendomucoscal resection. And in basic or limited settings, we would still recommend surgery in that setting following TME principles to achieve clear margins and a good surgical outcome, because we felt that, in basic-limited settings, the skill and the equipment necessary to do a local excision may not be available. Another recommendation that might highlight the differences between basic and limited settings versus a more maximal setting is the optimal strategy for post-treatment surveillance. So this is after resection of the stage 1 to 3 colorectal cancer. What would be the best way to monitor and surveil patients? And this is the recognition that the purpose of surveillance is to identify recurrence early at a time point where the patient may still be amenable to having local regional resection or resection of the metastatic lesion to change the outcome. So the current ASCO guidelines are to perform a medical history, and physical examination, and a CEA every six months for three to five years, have an abdominal and chest CT scan, in high-risk patients, every 6 to 12 months for three years, and a colonoscopy one year after the surgery, and then every five years or so after that, as indicated, up to age of 75. And that's what we recommended in the maximal and enhanced settings. But in a more basic setting, the recommendation was similarly medical history and physical exam every six months for three years, a CEA every six months for three years, a chest X-ray and abdominal ultrasound twice in the first three years, and a colonoscopy once i the first two years. And then if a colonoscopy is not available, we recommended a double-contrast barium enema or, for left-side tumors, a sigmoidoscopy to try to surveil the local regional extent of the the disease. So I think what we're trying to highlight is that we think that we can help patients for the management of localized early-stage colon cancer, both for treatment as well as for surveillance, and that these recommendations may vary a little bit in more limited settings, but with these recommendations, we can provide the best care for patients overall. And so why is this guideline so important? And how will it change practice? I think that the guideline is really important, because we recognize that we're practicing medicine in the United States, or in Europe, or wherever you practice, but the levels of resources that are available to us are not uniform. And so we really are getting to the aspect that cancer care is a global proposition. And ASCO should reflect that. And so the intention of these resource-stratified guidelines is to try to provide guidance into the best management for the indication across the spectrum of resources that are available. Interestingly, we've also heard from many people who practice in more resource-limited settings that they can use these guidelines to sort of advocate for their own area, to say that, based on our availability, we fit in a criteria that's basic or limited, but we really want to be an enhanced setting, and lobby their governments or their local officials to say, these are areas that we can improve on to take us to the next level, literally. And finally, how will these guideline recommendations affect patients? Yeah, at the end of the day, I think it's very important that we remind ourselves that we're doing this to improve patient care overall. I think, in maximal and enhanced settings, the guidelines kind of reiterate the best practices across [INAUDIBLE] of guidelines that were reviewed. So I think that's a very important thing. And they unify the treatment plan across different practices. But I think most importantly, in basic and limited settings, it provides a benchmark for what should be done. I think, for me, one key thing was that, even in basic and limited settings, we don't want to compromise oncology principles for a surgical resection. You know, it's not appropriate to just resect the tumor but leave some tumor behind to relieve an obstruction. We still need to manage that appropriately. And that is the expectation in a basic setting, for example. So I think that, overall, wherever you are, this guideline provides recommendations to help manage the patient across the resources that are available to you. I think that's very important, because we live in a heterogeneous environment where resources are not uniform across the world. Great, thank you for your discussion of this important guideline. And thank you for your time today, Dr. Shah. Oh, it's my pleasure. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr. Hayes interviews Dr. Muggia about his time at NCI. TRANSCRIPT: 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] Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network-- a collection of nine programs carrying a range of educational and scientific content, and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. [MUSIC PLAYING] Hi, and welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm the medical oncologist, and I'm also a researcher at the University of Michigan local cancer center. And I'm the past president of the American Society of Clinical Oncology. I am truly privileged to be your host for a series of podcast interviews with the founders of our field. Over the last 40 years, I've really been fortunate. I've been trained, mentored, and I've been inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired and gain an appreciation of the courage and the vision, and frankly, the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. I hope that by understanding how we got to the present and what we now consider normal in oncology, we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm pleased to have, as my guests on this podcast, Dr. Franco Muggia. He's generally considered one of the pioneers of new drug development oncology going all the way back to the 1960s. Dr. Muggia is currently a professor of medicine and co-chair of the GYN Cancer Working Group at NYU, and a member of their breast cancer program. He was born in Turin, Italy before the war. But when he was about three years old, his family fled to Ecuador to escape Mussolini's fascism. After growing up there at the age of 18, he moved to the United States in Danbury, Connecticut, to finish high school. And then he received his undergraduate degree in biophysics from Yale in 1957. In 1964, he became a US citizen. But he's remained true to his roots and has been very involved with both US/Italian cancer collaborations and mentorship, and also with South America for decades. He went to medical school at Cornell, followed by an internship at Bellevue in New York City, and a residency at Hartford Hospital in Connecticut. He completed a fellowship in medical oncology hospital in 1964-1967. And we're going to talk about that, Franco. And since he's had a number of important academic positions at Einstein, the NCI, University of Southern California, and New York University on two different occasions, and that's where he still practices. He's been involved in the development of clinical trials of hundreds of new drugs through the years, perhaps most notably, cisplatinum. In regards to ASCO, he served on our cancer education committee and on the editorial board of JCO. In fact, I understand you were the first editor of the Spanish edition of JCO. Correct. Correct. And perhaps more importantly, he's been a direct, and an indirect, mentor of hundreds of medical oncologists of the decades at that many institutions he's served, including myself, frankly, in my association with his good friend, George Canellos. Dr. Muggia, welcome to our program. Thank you very much, Dan. And I would just say, just a comment on the citizenship. So once I became a citizen, I actually became eligible for the draft. And that was the main reason why I ended up at the National Cancer Institute. So it had a-- it was a great effect on my career, that I actually volunteered for the Public Health Service in 1969. Because Lyndon Johnson changed the rules for physicians. And if you hadn't served, you had to serve up to age 35. So I decided I should join, not head to Vietnam like the rest of my classmates-- like many of my classmates from Cornell. And it really was a career change for me. Actually, that's a recurring theme in my podcast series. I have interviewed several people at the NCI in the mid to late '60s and early '70s sort of pejoratively, but actually not. You all became known-- as you've put in some of the things you've written-- as the yellow berets. Right. But in fact, it's really, I think, fundamentally changing-- NIH in general, and especially the NCI. We'll talk about that more later. I know your father was a pediatrician. Leaving Europe in the 1930s must have been extraordinarily painful for him and your family. Can you tell us more about that, and getting to Ecuador? Well, he was-- he never joined the fascist party. In fact, he was best friends with the socialists that remained at that time. Mussolini was brutal. He wanted everybody to become a fascist. And anybody who served at the University lost their jobs. He was in a bit of hot water as well. So that, plus the racial laws, which made Jews not be citizens, led to a big decision in the family. It was a phone call, whether we wanted to join an enterprise-- whether he wanted to join an enterprise in Quito, Ecuador in a pharmaceutical company. And my mother said, I don't know where the place is, but let's go. So that's how it happened. So in a matter of a few weeks, we were gone. And I was three years old. So how did you end up getting to Connecticut? Well, that was-- the American School of Quito, which I was a founding member in kindergarten. There was this person who became Ecuadorian, who was actually born in New York because his father was a consult here in the early 1900s, Galo Plaza Lasso. He decided, hey, we need a school-- a private school that-- non-religious, that competes with the German school that's there. We're going to call it the American School of Quito. So I was a founding kindergarten pupil, and ended up going right through to graduation with my class, except that the last year, I was an exchange student in Danbury, Connecticut. Because our principal, who was a champion swimmer-- Ashby Harper-- and John Verdery, who was at the Wooster School principal, they were together in Princeton. And they decided to make this exchange program, which ended when-- I was the last one, actually, of six years. My brother, he was there three years before. But they sent a person, or two people, to be there for their last year. And now I know you went on to Yale to study biophysics. I'm always fascinated by why people end up making decisions. So you were biophysics major. Why did you go into medicine? Was it your father? Well, my father and my two grandfathers were physicians, actually. So my brother was already-- he preceded me at the Wooster School, and then he went to Harvard College. I decided to go with some of the-- it was a small class. We had 16 people. Four of us went to Yale. So I decided to join the group that went to Yale. And my father thought that I should go into the sciences, but not medicine. One doctor was enough. So I started off, and I was actually doing very well in math and physics. And I was friends with a lot of premeds. But I didn't want to take any pre-medical-- the usual biochemical courses that were given at the medical school. So I decided to go with the head of biophysics major, and that suited me fine. So I started with that. And then I decided, well, you know, that's good. But let me head to medical school. So you had no choice. Actually, the really great story, I know you went to Cornell Medical School. Tell us about the lecture by Dr. Karnofsky, which I think has ended up changing oncology. Yeah, so-- yeah, actually, it was the first lectures we had in medical school as freshman. And we had-- in our 30th reunion a few years later, I talked about Karnofsky, how he inspired me to think about the clinical matters in cancer and his performance status evaluation. I remember that very well. Nobody else did. I have to tell you-- I guess it resonated with me, but not with my other mostly surgeons in my medical school. Well, this is, frankly, a recurring theme in these podcasts too, which is many of our pioneers hadn't thought about going into cancer. In fact, in those days, it almost didn't exist. And then one person made a light bulb come on. I have the same issue in my own career with Dr. Einhorn. So I think all of us need to keep in mind, you never know what influence you're going to have on a medical student. Yes, mentorship is extremely important. And going to class, face-to-face meetings are important. I know you've told me some of the stories too, but when you were at Cornell and located through Memorial, that you ran into some of the luminaries-- Joe Burchenal, Irwin Krakoff, Miriam Isaacs-- Well, I took-- well, that's partly mixed with my internship because I did my internship at Bellevue Cornell division. Yeah. And also, my clerkship. So yeah, that's when I took some electives, too, at Memorial as well. What did Miriam Isaac bring into this one? I think a lot of us know about-- Miriam Isaac was head of the metabolism group. Where did you know her from? I've just heard her name, yeah. Yeah, she was part-- Parker Vanamee and Miriam Isaac ran this physiology. It was called physiology elective. And it was ideal for a third year student. I learned everything, because you saw so many derangements that were concomitant with what was happening with the progression of cancer. But they examined all the issues regarding what led to hyperuricemia, hyperkalemia, any electrolyte imbalance. So you really learned a lot. So that almost gets to the birth of translational medicine, in many respects. We think this is new. It's not. It goes way back. Right. It goes way back. I know then you went on and finished your residency. And most importantly, you are an alumnus of the Francis Delafield Hospital. And that spurred me. I've heard this hospital's reputation my entire career. But I never knew who he was, or what it's all about. Tell us about-- Well, so the city of New York, the city of New York, they really had very good outstanding commissioners of health who decided that cancer hospitals were important to take care of New Yorkers with cancer. And they set up one at Cornell, which was called James Ewing Hospital, which was right inside Memorial Hospital. So they were-- I mean, people don't really remember the James Ewing Hospital because it was annexed into Memorial Sloan Kettering. But the one at Columbia was a separate building. And it was Francis Delafield Hospital. And it had real luminaries from the Columbia faculty, including Alfred Gellhorn, who was a professor of medicine and very charismatic. It was an outstanding group of individuals. Gellhorn presided over a group of about 10-12 internists who were dedicated to cancer and also translational research, as you say. And one of my papers that I wrote to my fellows was on hypercalcemia malignancy with Henry Heinemann, who was one of the internists. He devoted all his effort into physiology, so to speak. So it was kind of the same segue to what we I had at Memorial as a student. But the Francis Delafield Hospital had problems. They had staffing problems because the head of medicine would not send their residents to-- stop sending their residents through the oncology services-- I guess that's what it would be, if you're taking care of medical oncology services. They were in all that way. But it was the Department of Medicine at Francis Delafield. And it was kind of a bit of envy, in part, as one interprets, that Gellhorn was so popular with the students. And so there was all this internal discord with these services at Columbia and Francis Delafield, although Francis Delafield was part of Columbia. So at one point, when the residency finally stopped including, the Bellevue first division residents did rotate through. The first division residents were Columbia service at Bellevue. And they rotated through. So when Gellhorn and another name, the president of ASCO later, Jon Altman-- who was a terrific teacher whom I worked with-- he then left and went to the University of Chicago. And Gellhorn left and became dean at the University of Pennsylvania. I was told to get another job. I was there, starting to be an attending physician. And I went to Albert Einstein. So as you see, I've moved around. I've moved around a lot, but I've moved around always twice to the same place, except the University of Southern California. And there, I go every year. I've maintained my ties with the Trojans. I know that Ezra Greenspan came out of there, and Jim Holland. Jim has told several of us this story, that he was in the military. And when it ended, he thought he was going to go back and be an internist with Dr. Loeb at Columbia at the main hospital. Dr. Loeb called him, and told him there was no space. And why don't you go work at Francis Delafield? And apparently, Dr. Loeb said because somebody always gets mental problems or tuberculosis. And we have to replace them anyway. And so Holland went to Francis Delafield and took care of a young girl with leukemia who sadly died. But it changed his life. That's what made him go into oncology. I deeply regret that I won't get the interview Jim Holland. Yeah, Jim Holland was the first alumnus of that program of the Francis Delafield Hospital. And, yeah, 10 years before I went there. And Jim and I remained friends for many years. We had that friendship in common. Jim gave a-- he was an extremely articulate individual. And when Alfred Gellhorn died in 2007, he gave one of the most touching memorials in his honor. We actually interacted recently through various collaborations here in New York, with first, Jim Holland set up this New York gynecology/oncology group. He was kind of the leader in that, even though he was not involved in gynecology. But he loved to host a group-wide effort. And it happened to coalesce first in gynecologic oncology, because everybody-- they all loved Jim Holland, teaching the gynecologists, but chemotherapy in general. And he's a great leader. So he became very active in the Chemotherapy Foundation, which is a New York foundation, and spoke at the meetings. And his wife, Jenny Holland, was on the board of the Chemotherapy Foundation. We gave them-- we gave Jim an award last year in November, of the Chemotherapy Foundation, for scientific excellence. And he gave one the most unbelievable talks there. Everybody who was there, which were fellows from the New York institutions and lay audience that was there at that event, they really learned a lot by Jim's presence. And unfortunately-- unfortunately, two months later, Jimmy Holland passed away-- less than two months. And of course, Jim passed away in March of 2018. We all miss him. And any of us who had been to the Chemotherapy Foundation, especially when Dr. Greenspan was running it, I always loved that meeting. Actually, when you were at Francis Delafield, what was giving chemotherapy like? It can't be as well-organized. Well-- [LAUGHS] Well, it was organized in the lymphoma service, which John Altman ran. And I was-- so my fellowship at Francis Delafield, it was a bit unusual. It was six months of hematology, six months chief resident, six months again hematology/general oncology, then six months chief residency. So we were involved during the fellowship in running some of the-- and orchestrating the work for the medical residents. In our spare time, we did work in the clinics. And in hematology, I worked with Jon Altman. Did you guys mix up your own chemotherapy in those days? Oh, sure. Yes. Well, that went on when-- actually, that went on when I became attending here at New York University. When I came back from the NCI, we mixed the chemotherapy. So yes. Our younger colleagues don't know this. Nowadays, it's all the pharmacists do it. And the nurses hang it up and start the IVs. And in those days, you guys were on the front lines doing the whole thing, right? Yeah. I mean, we gave vinblastine primarily, but the clinic stereo was vinblastine that we gave. Because the other drugs were procarbazine, nitrogen mustard, of course. There is Chuck Martel of Mayo Clinic fame and florouracil fame. He said he used to do morning rounds to give florouracil at the Mayo Clinic. I don't know who mixed the florouracil for him. I mean, it came in already mixed. But he used to deliver the drugs. Life was different then. Actually, I want to change tracks a little bit, and that is because I know you had a lot to do with the development of supplying them when you were at CTEP at the NCI. You and I were fortunate enough to get to attend the 40th anniversary of the approval of cisplatinum by the FDA. It was held in east Lansing. And that's because Professor Barnett Rosenberg discovered it at Michigan State. Can you give me just some history of that, of what your role was, and why Dr. Rosenberg thought that cisplatinum was a good idea in the first place? Well, I mean, it goes of the drug development program, which was one of the major efforts of the chemotherapy program that was the first program that had oncology involved in it. It was mostly the team in lymphoma, with Gordon Zubrod being the head. And he's the one who recruited Fry/Frederick, and then Carbonne/DeVita group. And they were doing the clinical oncology part. Drug development was a very much part of it. And of the drugs that-- they developed drugs for some of the pharmaceutical industries because pharmaceutical industries had no trials. They had their own pipeline. Now their own pipeline had drugs like nitrosoureas, which didn't go anywhere, and dacarbazine. They were not so robust related to the screens that they used for drug development. But they also had drugs from academia and from the Department of Agriculture. And from academia, they got cisplatin, which was isolated by Barnett Rosenberg at Michigan State, as you heard in that great event that they had, the 40th anniversary of its approval. And he was running electrical currents in bacterial cultures and found that the bacteria were developing-- stopped dividing and developing filamentous forms, which were very unusual. And then he thought it was electricity at first, but then only platinum electrodes had that property. And he and his co-workers made the right assumption that it was platinum. They isolated cisdichlorodiamine dichloroplatinum which was known from a century before to be an inorganic platinum salt. That drug, when I was first at the NCI, my first tour duty as a senior investigator, was broadcasted because it had tremendous anti-tumor activity in the screens. And so when there were press releases, like it often happens, lay people call in and they want the drug for their relatives, or for themselves. And I remember answering phones and saying, no. We don't have that drug. It hasn't been given to people. But the story in 1972, the phase I study was-- I attended the ACR, where they presented. Chuck [? Kerlia, ?] from the University of Illinois, he did the first study. And it had activity. But it bumped off some kidneys and some hearing. And I said, well, who needs a drug in head and neck cancer, or Hodgkin's, where you have such terrible toxicities? Well, guess what? I was wrong. First, you deal with the cancer, then you deal with the toxicity. But it was Jim Holland. Actually, Higby, Don Higby, who worked with Jim Holland at the Roswell Park in the Holland service, who identified remarkable activity in testicular cancer. And that's what carried it. And then Larry Einhorn, of course, carried the ball on that on the development of cisplatin in testicular cancer. The group in the [INAUDIBLE] showed tremendous activity. Eve Wilshaw showed tremendous activity in ovarian cancer, but not quite curative, which is an interesting facet. And then, well, the rest is history. The FDA, that was my second time at the NCI. I had the pleasure of sitting with Vince DeVita at the FDA with Bob Kraut, who said, no, this drug is too toxic. You've got to do some randomized studies. And that was 1978 then. Vince pounded the table and said, the best thing that's happened to oncology, you can't recognize it? You know, there's something wrong with your procedures. So that led to some rethinking. And sure enough, it was approved. No need for randomized studies, given that it was curing testis cancer, but a need for educating how to deal with and cope with the toxicities. Actually, I have-- So that's the story of cisplatin. And it was even further detailed by-- when you were there at that meeting-- by Larry Einhorn and his patient. Yeah. Actually, I have three remarks to this. One is that when I was a fellow, Dr. Fry used to teach us that if the drug works and is curing cancer, we'll figure out the toxicities later. That's a little ruthless, but it's always stuck with me. Yeah. Yeah, we don't want to say it too loudly because toxicities are very important in anything you do. But of course, if you are-- you know, if it's the last resort you're looking for, for something to help the patient-- and it is helping-- you kind of have to bite the bullet sometimes. Those were the days where we had many cures anyway. The other thing that struck me at that meeting is cisplatinum is now used in more than half of all cancers-- adult cancers. I didn't realize it was that common. But that's true. The other thing that I didn't realize, that the number of publications continued in research, continued to increase more than imatinib and trastuzumab. Yeah. And that's the other thing I heard. And the final thing, just, if there are any chemists listening, to get lucky from all this-- it turns out, that trans-diaminoplatinum doesn't work, and cisdiamine does-- dichloro, I'm sorry. And the reason why is entry into the cells, is that the trans doesn't get in the cells. And the cis does. And it just goes to show how important that clinical chemistry is in our drug development. I think a lot of us forget that in the pharmacology. Right. There are actually a lot more things to learn in how the platins interact with DNA. Yes. Actually, another layer I want to go into is your importance and the really remarkable growth in the cooperative groups in the late '90s. Can you kind of give us a brief history starting in 1955, when Drs. Fry and Frederick and Holland started? And then what your role was later on in making it really take off? You're talking about the chemotherapy program? Well, weren't you involved with the qualitative groups and-- With our comparative groups, yeah. Oh, yeah, they came together. Yes, no, for sure. I was there first as an intramural person. And I was briefly on loan to the solid tumor service with Vince DeVita and George Canellos. And then I was in their new-- Paul Carbone had put me in the lung cancer study group there, that led on. So I was strictly intramural. When I returned to Einstein after to doing my service, Vince DeVita became the director of the Division of Cancer Treatment, which is the evolution of the chemotherapy program. As director of the division, he gave me a choice of couple of positions. And I actually took the cancer therapy program position as his associate director for CTEP. His predecessor had been-- my predecessor in that position had been Steve Carter. I don't know if you know about Stephen Carter. No, I met Dr. Carter. He was encyclopedic in the knowledge of all the trials that were done in the-- sponsored by the National Cancer Institute and also abroad. So he became a great face of the NCI internationally. And he spurred the development of the EORTC as well. So that was developed initially through a grant of the National Cancer Institute. So he was involved in the EORTC. But the cooperative groups had started during the leukemia program with the acute leukemia group B, which was the counterpart of acute leukemia group A, which was the intramural program. Jim Holland became the chair of the group. He was such an inspiring leader of the cooperative group. His cooperative group was amazing, to go to one of his meetings, which lasted two afternoons. He really commanded-- it was like a plenary session, and doled out all the projects in one afternoon. And then, in the second day, they kind of review whatever had developed. But other groups started. And the Eastern Cooperative Oncology Group became-- I had joined that when I had gone back to Einstein. It developed under founder Paul Carbone. He had assumed chairman-- no, Paul Carbone became the chairman later on. Initially, it was run by-- it'll come to me right now. I have a lapse on who was the group chair. But it was kind of Boston nurtured. And they were primarily devoted in solid tumors. And they started with making inroads into solid tumor beyond the acute leukemia. But in GI, for example, where I was in the GI committee, Chuck Martel did a number of studies. He ran those meetings, floated ideas. A week later-- we didn't have emails, but a week later, he had the protocol on your desk. Let me ask you a final question, to begin to tie it up here. When you were at the Delafield and then at the NCI, was there a sense that you guys were doing historic stuff? Or was it just day-to-day, same old, same old. Then you look back and say, boy, look what we did. Was there a sense that something big was happening in those days? Oh, no. There was always a sense. Well, when senior investigators, there was always a sense there are a lot of things here developing of interest, you know? And there was a full head of steam in part related to the combination chemotherapy. Now in acute leukemia, it was obvious. But the big thing about the solid tumor service since DeVita and Tom Fry, who started the work in lymphomas. Peter Wernick, George Canellos, they found that the combination chemotherapy did something in lymphomas, and also later on with, also, Jim Holland's work. And you've mentioned Ezra Greenspan. They had seen that combinations of drugs did help, to a large degree, breast cancer. Now the same drugs didn't tried to be extended-- the same principles-- to other solid tumors. It didn't work so well. But breast was somewhat sensitive to the drugs, the alkylating agents and the antimetabolites. So those were the first combinations, and the vinca alkaloids. Let me ask you this, my final question. But I've been a breast cancer guy all my life. And Cushman Haagensen, of course, is a giant. That's the name from the past. Yes. So when you were at Delafield, did he try to oppose the chemotherapy because he felt that a chance to cut is a chance to cure? I mean, he was one of the biggest knives of all time. Yes. Actually, no, he opposed it for different reasons. I never understood why. He didn't only oppose chemotherapy, he opposed hormone therapy, which was coming along. Because he thought that any sex hormones were detrimental to the course of disease. But it was also mostly rivalry with a medical service, I think. Because we saw responses. I did my first trial with progestational agents. So I did some clinical trials, actually, when I was a fellow. So we published an observational series of patients treated with medroxyprogesterone acetate, and presented at the American College of Physicians in '67. So you know, he opposed Gellhorn's intervention in breast cancer medical intervention. He liked to give steroids. And we used to see the patients because the patient developed diabetes. So that's how we got involved in some of the disseminate at the patients with metastatic breast cancer. He wouldn't refer them. So I got involved because I saw a lot of diabetes. And then we started our own treatments. We bonded with the patients and started our own treatments. Again, a recurring theme is how much courage it took for you and your predecessors to do what you do. And the confrontation, if not hostility, between the surgeons. I have to say, that what that really does is it brings up Bernie Fisher and Umberto Veronesi, and the courage they had to adopt systemic therapy as opposed to obstruct it. I don't think our younger colleagues are aware of the battle. Oh, yeah, no. Bernie deserves a lot of credit. And I can tell you of arguments he had with Jerry Urban and other surgeons when he came to a meeting in New York. And Sam Hellman was there. He said, Bernie, we agree with you. I think it's taken us some time to process what you just-- the great thing you have done, to rely on other than surgery. Because they came after him, even I'm talking early 1980. Oh, I was at a meeting. I was at a meeting maybe '83 or '4. It was the first time I'd ever met Dr. Fisher. And he and Urban were sharing a podium. I thought there was going to be a fistfight. Yes. I mean, it was really contentious. And that was an eye-opener for me, where I thought, there's a surgeon up there telling us we should do things that will put him out of business. That's a very interesting approach. Well, yes. And the one thing about Bernie Fisher, he understood trials. And I remember, they said-- Jerry Urban said, why do you think that that curve isn't just going to go down and plummet? He said, it's called probability, Doctor. [CHUCKLES] All right. Well, we've run out of time. I hate to say that because these are great stories. But I want to thank you for taking time. Thank you, Dan, for the interview, for sure. And we do share some common background. And we didn't get to talk about all the international things that came out of the National Cancer Institute. As Jim Holland said in that congressional hearing, the National Cancer Institute was the best international weapon we have had. Yeah, I think that's a great point. And I do regret we've run out of time here. Maybe we can do that in another interview. But I want to also thank you for all you've done for the field and the hundreds of people you've trained. I don't go anywhere where I don't bring up your name, and somebody goes, oh, yeah. I worked with that guy. Well, that's a motive a great satisfaction, I have to say, for sure. It takes just the ability to listen to what your fellows are saying and responding to them. Yeah. That's been my secret. And you're very good at that. I've seen you in action. So thanks again. I appreciate this, and look forward to seeing you soon. Thank you, Dan. I appreciate very much all your questions, and your interview, and your friendship. [MUSIC PLAYING] 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 a review on Apple Podcast, 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 the shows at podcast.asco.org. [MUSIC PLAYING]

A cirurgia é o principal tratamento para pacientes com metástase hepática de câncer colorretal? O que você acha? Se você quer saber mais sobre esse assunto não perca este mais novo episódio do Clinical Papers Podcast! Eu e Tiago discutimos o famoso EORTC 40983 (um atualização do famoso EPOC Trial de 2008). Com um resultado surpreendente esse paper gera muita discussão em torno do assunto. Com mais de 350 pacientes randomizados, o EORTC 40983 é um estudo multicêntrico, randomizado com mais de 70 Centros distribuídos pela Europa, Austrália e China. Não perca a discussão do paper e tire suas próprias conclusões. Quimioterapia peri operatória + Cirurgia vs. Cirurgia isolada? Quem vencerá essa disputa!?!? Tenha acesso ao paper pelo link: https://www.ncbi.nlm.nih.gov/pubmed/24120480

This JCO Podcast provides observations and commentary on the JCO article “PET Score Has Greater Prognostic Significance Than Pre-Treatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK NCRI RAPID Study” by Barrington et al. My name is Brue Cheson, and I am at Georgetown University Hospital, Lombardi Comprehensive Cancer Center. My Hematologic-oncologic specialty is Lymphoma.   Hodgkin lymphoma is clearly one of the most dramatic success stories in modern oncology. More than 90% of patients with limited disease and about 85% with advanced disease are cured using conventional chemotherapy regimens.  As a consequence, current clinical trials are focusing on augmenting or modifying treatment for those at higher risk and decreasing the intensity or duration of therapy for those at a lower risk of treatment failure.   One important question has been: how best to distinguish those disparate groups?  Over the years, various prognostic scoring systems have been devised.  The International Prognostic Scoring System (IPSS) differentiated patients into 6 groups using 7 clinical and laboratory factors.  However, only 7% of patients are in both the most and least favorable groups.  The German Hodgkin study Group (GHSG) and the EORTC each published criteria slightly different from each other for treatment selection.  Nevertheless, it is not clear that any of these schemas remains relevant in the context of current Hodgkin regimens.  More importantly, they do not reliably dictate how to treat patients, nor do they offer therapeutic targets.   FDG-PET scanning has revolutionized our management of patients with lymphoma.  In 2005 we first demonstrated that integration of PET into standard response assessment improved the ability to distinguish between residual tumor and fibrosis in patients with diffuse large B-cell lymphoma, leading to a revision of standardized response criteria. More recent studies have confirmed this observation in Hodgkin lymphoma and other histologies. Patients with advanced Hodgkin lymphoma can be distinguished into high and low risk groups based on PET scan results after 2 cycles of standard ABVD chemotherapy, regardless of their pretreatment IPSS score.  In a number of studies, reacting to the positive interim scan by intensifying therapy achieved outcomes markedly improved over expected.   In the paper that accompanies this podcast, Sally Barrington and her colleagues performed a secondary analysis of the RAPID trial to evaluate the role of pre-treatment risk factors and PET results in predicting outcome of patients with early stage Hodgkin lymphoma.  This study accrued 602 patients who were treated with standard ABVD and underwent PET scanning after the third cycle.  Those with a negative scan (a Deauville score of 1-2) were randomized to no further treatment vs involved field radiotherapy.  Despite a failure to demonstrate non-inferiority of progression-free survival in this cohort, the overall survival was the same, thus sparing 90% of patients unnecessary radiotherapy.  Those with a positive scan (defined as a Deauville score of 3-5), the primary focus of the current manuscript, received an additional cycle of ABVD plus radiotherapy.  Only the 21 patients with a Deauville score of 5, defined as an SUV at least 3 times greater than that of the liver, had an inferior time to progression or greater risk of Hodgkin-related death.  Importantly, this finding was independent of pretreatment prognostic factors using either the GHSG or EORTC scores.  Whether this observation can be extrapolated to patients with features not eligible for the RAPID study, such as those with bulky mediastinal disease or B-symptoms, is presently unknown.  Nonetheless, these data support the role of metabolic imaging over standard clinical and laboratory risk factors.   But we are clearly doing this all wrong.  Why do we treat all patients the same and then wait until the disease has demonstrated resistance before we alter therapy?  Several recent papers support the notion that anticipatory, biologically-based, risk-adapted approaches may be feasible. Pre-treatment total metabolic tumor volume (defined as the sum total of all metabolically active lesions) can predict outcome in Hodgkin lymphoma as well as follicular, diffuse large B-cell and primary mediastinal large B-cell lymphoma.  High heterogeneity of intratumoral FDG uptake distribution on PET-CT may be a marker of chemoresistance in solid tumors as well as various lymphoma histologies.  Unfortunately, those tests do not provide a target against which to direct a specific agent.  In contrast, a number of investigators have demonstrated a correlation between bcl-2, p53, FOXP3, CD68, STAT1, pattern of PD-1 expression, mutational patterns derived from next generation sequencing, and other factors in pre-treatment Hodgkin node biopsies and outcome.  Thus, if we are able to predict outcome prior to treatment, why do we expose patients to drugs to which we know they will not benefit? The goal of treatment should be anticipatory, risk-adapted strategies whereby patients with a high likelihood of benefit may receive standard of care, unless there is another clinical question being addressed.  On the other hand, those unlikely to benefit as determined prior to therapy should be spared the waste of time and toxicity and treated with novel regimens directed at specific targets.  Both groups should be monitored during treatment for the emergence of mutations, with treatment altered accordingly.  Yes, we may be a long way from having the appropriate tools for such an approach.  But, to quote the geneticist, molecular engineer and chemist George M. Church, “The best way to predict the future is to change it”.  Anticipatory, risk-adapted strategies could do just that.   This concludes this JCO Podcast. Thank you for listening.

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. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Manish Shah from New York Presbyterian Weill Cornell Medical Center, senior author on "Treatment of Patients with Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline." Thank you for being here today, Dr. Shah. Thank you, it's a pleasure and honor to be here. So first, can you give us a general overview of what this guideline covers? Yes, absolutely. So the "Treatment of Patients with Early-Stage Colorectal Cancer" is a resource-stratified guideline. And it focuses on the management of patients with early-stage colon cancer. It's different than the surveillance and screening guideline that was written simultaneously for ASCO as another resource-stratified guideline. We felt that this was a big enough topic that we should keep it separate. So it really talks about the management of pre-malignant lesions, as well as early-stage colon cancers, as well as rectal cancers. And the other aspect of this is that we really focused on how the guideline may apply in settings where there-- they don't have maximal resources, so basic or limited settings as well. So I would like to talk a little bit about how the guideline was created, because I think that's an important aspect. And it distinguishes it from typical other ASCO Guidelines. So the management of colon cancer or colorectal cancer, there's a lot of literature on this. And there are several guidelines that have been produced by colorectal cancer societies, or surgical societies, or from other countries like the EORTC, or Japan, or Korea, or even the UK. So in fact, there were, I think, 30 to 40 different guidelines that we reviewed. And we felt that, instead of doing a new literature search to kind of rehash much of the same information, we reviewed all the guidelines for certain quality measures to then select a handful of guidelines that we would use as the reference for each of our key questions or key points. And this was done in a formal process, the first by ASCO and Sarah, who was the ASCO staff who wrote the guideline, along with the members of the guideline panel. And in this process, I think that we have a pretty comprehensive guideline that covers the questions with the best evidence available. So what are the key recommendations of this guideline? Yeah, so we addressed some several questions with regard to key recommendations. The first question, for example, was, what's the optimal treatment for patients with colon cancer that would be clinical stage 1 through 3c? And we distinguish that from a non-obstructing cancer to obstructing cancers as well, because the management would be very different. And what we really sort of focused on is that these patients should have resection following oncologic principles. Then ideally, they should have an en bloc resection by a surgical oncologist to give the patients the best chance of care. But I think what's unique to resource-stratified guidelines, and what we have to do is sort of highlight the care that would be achieved in settings that have less resources. So a non-obstructing colon cancer in a basic setting should still have surgery and should still undergo an en bloc resection following standard oncologic principles. So that was, for example, one of the key points that was uniform across all the settings. Other things were how to manage [INAUDIBLE] colon cancer. So in more enhanced and maximal settings, sometimes there might be opportunity to place a colonic stent, for example, by either a colorectal surgeon or by someone who has specialized training in the placement of these stents. And that would be a preferred approach in both the enhanced and maximal guidelines, whereas in a more basic setting, the recommendation was to perform a resection and possibly, if required, if a resection was not possible, a diversion to overcome the obstruction in that localized setting. There were other recommendations that were also important. So for example, in early-stage rectal cancer, so clinical stage 1, T1 and 0 rectal cancer, in a maximal setting, these are sort of low-risk cancers without adverse features like high-grade or involvement of lymphovascular structures. The surgical oncologist and/or colorectal surgeon might consider a local excision such as the TEM procedure, which is a transendomucoscal resection. And in basic or limited settings, we would still recommend surgery in that setting following TME principles to achieve clear margins and a good surgical outcome, because we felt that, in basic-limited settings, the skill and the equipment necessary to do a local excision may not be available. Another recommendation that might highlight the differences between basic and limited settings versus a more maximal setting is the optimal strategy for post-treatment surveillance. So this is after resection of the stage 1 to 3 colorectal cancer. What would be the best way to monitor and surveil patients? And this is the recognition that the purpose of surveillance is to identify recurrence early at a time point where the patient may still be amenable to having local regional resection or resection of the metastatic lesion to change the outcome. So the current ASCO guidelines are to perform a medical history, and physical examination, and a CEA every six months for three to five years, have an abdominal and chest CT scan, in high-risk patients, every 6 to 12 months for three years, and a colonoscopy one year after the surgery, and then every five years or so after that, as indicated, up to age of 75. And that's what we recommended in the maximal and enhanced settings. But in a more basic setting, the recommendation was similarly medical history and physical exam every six months for three years, a CEA every six months for three years, a chest X-ray and abdominal ultrasound twice in the first three years, and a colonoscopy once i the first two years. And then if a colonoscopy is not available, we recommended a double-contrast barium enema or, for left-side tumors, a sigmoidoscopy to try to surveil the local regional extent of the the disease. So I think what we're trying to highlight is that we think that we can help patients for the management of localized early-stage colon cancer, both for treatment as well as for surveillance, and that these recommendations may vary a little bit in more limited settings, but with these recommendations, we can provide the best care for patients overall. And so why is this guideline so important? And how will it change practice? I think that the guideline is really important, because we recognize that we're practicing medicine in the United States, or in Europe, or wherever you practice, but the levels of resources that are available to us are not uniform. And so we really are getting to the aspect that cancer care is a global proposition. And ASCO should reflect that. And so the intention of these resource-stratified guidelines is to try to provide guidance into the best management for the indication across the spectrum of resources that are available. Interestingly, we've also heard from many people who practice in more resource-limited settings that they can use these guidelines to sort of advocate for their own area, to say that, based on our availability, we fit in a criteria that's basic or limited, but we really want to be an enhanced setting, and lobby their governments or their local officials to say, these are areas that we can improve on to take us to the next level, literally. And finally, how will these guideline recommendations affect patients? Yeah, at the end of the day, I think it's very important that we remind ourselves that we're doing this to improve patient care overall. I think, in maximal and enhanced settings, the guidelines kind of reiterate the best practices across [INAUDIBLE] of guidelines that were reviewed. So I think that's a very important thing. And they unify the treatment plan across different practices. But I think most importantly, in basic and limited settings, it provides a benchmark for what should be done. I think, for me, one key thing was that, even in basic and limited settings, we don't want to compromise oncology principles for a surgical resection. You know, it's not appropriate to just resect the tumor but leave some tumor behind to relieve an obstruction. We still need to manage that appropriately. And that is the expectation in a basic setting, for example. So I think that, overall, wherever you are, this guideline provides recommendations to help manage the patient across the resources that are available to you. I think that's very important, because we live in a heterogeneous environment where resources are not uniform across the world. Great, thank you for your discussion of this important guideline. And thank you for your time today, Dr. Shah. Oh, it's my pleasure. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

BARCELONA—Not only was breast conserving therapy safer than mastectomy for most low-risk patients in the large randomized EORTC 10041/BIG 03-04 MINDACT trial reported at the 2018 European Breast Cancer Conference but also many patients could be advised to avoid chemotherapy …Emiel Rutgers AJO PRODUCTION MASTER

Prof Eggermont speaks with ecancertv at ESMO 2016 about results from the EORTC 18071 phase III trial of ipilimumab, an anti-CTLA 4 immune checkpoint inhibitor, as an adjuvant therapy for patients with high risk stage III melanoma. Prof Eggermont describes the improved overall survival rate of five years, 11% high in the ipilumumab arm, as coming at the cost of immune related side effects associated with ipilimumab.

Drs. Leora Horn, Ben Solomon, & Jack West debate whether results from a European trial of chest radiation after chemotherapy for extensive stage small cell lung cancer should lead to a change in treatment for this setting.

Drs. Leora Horn, Ben Solomon, & Jack West debate whether results from a European trial of chest radiation after chemotherapy for extensive stage small cell lung cancer should lead to a change in treatment for this setting.

Drs. Leora Horn, Ben Solomon, & Jack West debate whether results from a European trial of chest radiation after chemotherapy for extensive stage small cell lung cancer should lead to a change in treatment for this setting.

Prof Philip Poortmans - University Medical Center, Nijmegen, The Netherlands Dr Poortmans talks to ecancertv at ECC 2015 about tackling the global shortfall in radiotherapy seen in a Lancet Oncology Commission report. He also discusses the 20-year follow-up of the EORTC 'boost no-boost' trial. The results showed that young age, high-grade invasive disease and ductal carcinoma in situ were all markers for benefit from a later boosted radiation dose in women with early breast cancer undergoing radiotherapy after breast conserving surgery.

Dr Conny Vrieling - Clinique des Grangettes, Geneva, Switzerland Dr Vrieling talks to ecancertv at ECC 2015 about a substudy of the 1,616-patient EORTC 'boost no-boost' trial, focusing on the impact of pathological factors on long-term local control in women with early breast cancer undergoing radiotherapy after breast conserving surgery, some of whom who were given an additional dose of radiotherapy. Young age, high-grade invasive disease and ductal carcinoma in situ (DCIS) were factors increasing the local recurrence rate. However, in patients with all three of these negative prognostic factors, giving the additional boost of radiation reduced the local relapse risk by almost 80% (hazard ratio of 0.21). These long-term results show the important and ongoing negative influence of additional DCIS on local control, Dr Vrieling says. The radiation boost continued to have a positive effect on local control after adjusting for systemic therapy, even after 5 years.

ecancer's Gordon McVie talks to Anastassia Negrouk, of the European Organisation for Research and Treatment of Cancer (EORTC), at ESMO 2014 on managing data in clinical trials and encouraging more personalised medicine to take place for the progression of cancer care.

Prof Eggermont (Gustave Roussy, Villejuif, France) speaks to ecancertv at ESMO 2014 about the EORTC 18071 trial, an efficacy study of ipilimumab vs placebo to prevent recurrence after resectable melanoma. The study demonstrates that ipilimumab has a significant impact on relapse-free survival over time, providing a significant survival benefit.

At ASCO 2014, Dr O'Day provides ecancertv with his expert opinion on the final analysis on the impact of ipilimumab on relapse-free survival from a randomised phase III study, EORTC 18071, which indicates that adjuvant (post-surgery) therapy with ipilimumab for patients with high-risk stage III melanoma decreases the relative risk of cancer recurrence by roughly 25 percent compared to placebo.

Added to the complexity of the widening variety of vaccines that are in current clinical trial for human cancers, and the increasing sophistication of our tools for assessment of the immune response underlying these vaccine interventions, this podcast discusses the elements of trial design and reporting in relation to the trial EORTC 18961.

This JCO Podcast provides observations and commentary on the JCO article, "Randomized Phase III study comparing Paclitaxel Cisplatin Gemcitabine and Gemcitabine Cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC 30987 Intergroup Study" by Joaquim Bellmunt et al. It provides my perspective that considers both statistical metrics and clinical outcomes in decision making for difficult to treat diseases.

Das Lungenkarzinom gehört in den Industrienationen zu den häufigsten Krebserkrankungen des Menschen. Als nachweislich gewichtigste Ursache für diesen Umstand steht der Zigarettenkonsum. Die Inzidenz der Neuerkrankungen nimmt bei den Frauen stetig zu, bei den Männern ist seit den 80igern ein leichter Abwärtstrend zu verzeichnen. Aufgrund der sehr unspezifischen Symptome beim Lungenkarzinom wird die Diagnose häufig erst sehr spät gestellt. Eine Operation kommt im fortgeschrittenen Stadium oft nicht mehr in Frage, weshalb die Therapie sich meist auf Radio- und Chemotherapie beschränkt. Obwohl die Therapie der vorliegenden Studie einen primär kurativen Ansatz hat, wird bei den meisten Patienten keine komplette Remission des Tumors erreicht und die Therapie bleibt palliativ beschränkt. Insbesondere in der Palliativmedizin gewinnt die Betrachtung der Lebensqualität der Patienten immer mehr an Beachtung. Wichtig sind nicht ausschließlich Überlebensraten und Toxizität sondern auch die subjektive Lebensqualität des Patienten. Der Patient als Individuum rückt in das Zentrum des Interesses. In der vorliegenden Dissertation wird die Lebensqualität im Verlauf von Patienten mit inoperablen NSCLC im Stadium IIIA und IIIB nach erhaltener Radiotherapie oder simultanen Radio- und Chemotherapie untersucht. Es handelt sich um eine prospektive multizentrische Phase III Studie. Die Studienpopulation setzt sich aus 303 Patienten zusammen. Zunächst erfolgte eine sechswöchige Induktions-Chemotherapie, die in zwei Zyklen mit Paclitaxel und Carboplatin durchgeführt wurde. Danach wurden die Patienten in zwei Behandlungsarme randomisiert, eine alleinige Radiotherapie oder eine simultanen Radio- und Chemotherapie, die ebenfalls sechs bis sieben Wochen andauerte. Die Lebensqualität wurde mittels dem Fragebogen QLQ-C30 von der EORTC aus Brüssel erfasst. Die Ergebnisse favorisieren die simultane Radio- und Chemotherapie. Es lässt sich ein signifikanter Unterschied der gesundheitsbezogenen Lebensqualität zwischen beiden Behandlungsarmen nach der Therapie feststellen. Die Patienten im Behandlungsarm der simultanen Radio- und Chemotherapie beurteilen ihre Lebensqualität im moderaten Maß besser als Patienten im Behandlungsarm der alleinigen Radiotherapie. Durch die simultane Radio- und Chemotherapie mit Paclitaxel kann die gesundheitsbezogene Lebensqualität der Patienten mit inoperablem nicht-kleinzelligen Lungenkarzinom im Stadium IIIA oder IIIB statistisch signifikant und klinisch relevant verbessert werden.

Die vorliegende Arbeit untersucht die Lebensqualität von 49 Patienten mit Akuter Myeloischer Leukämie (AML) und Myelodysplastischem Syndrom (MDS), die im Rahmen der AMLCG99-Therapiestudie an der Medizinischen Klinik III am Universitätsklinikum München, Standort Großhadern, behandelt wurden. Als Instrument zur Erfassung der Lebensqualität diente der QLQ-C30-Fragebogen der EORTC. Ziel der Arbeit war die Untersuchung der zeitlichen Veränderungen der Lebensqualität der Patienten, der Vergleich mit der deutschen Normalbevölkerung und die Beschreibung von Einflussfaktoren auf die Lebensqualität. Zu Beginn der Therapie war die Lebensqualität der Patienten in fast allen Skalen deutlich schlechter als die der Normalbevölkerung. Im weiteren Therapieverlauf kam es jedoch zu einer Verbesserung der Lebensqualität in den meisten Skalen. Dennoch zeigten die Patienten ein Jahr nach abgeschlossener stationärer Therapiephase in vielen Skalen statistisch signifikant schlechtere Werte und klinisch noch mäßig bis sehr große Unterschiede zur Normalbevölkerung. Einzig der allgemeine Gesundheitsstatus, die physische Funktion sowie wenige Symptomskalen unterschieden sich zu diesem Zeitpunkt nicht mehr von der Normalbevölkerung. In der Subgruppenanalyse zeigte sich, dass ein Jahr nach Beendigung der stationären Therapiephase ältere Patienten Lebensqualitätswerte erreichten, die sich von der Normalbevölkerung entweder nicht mehr unterschieden oder sogar besser waren. Auch nicht allogen transplantierte Patienten zeigten in beinahe allen Skalen Werte, die sich nicht mehr von der Normalbevölkerung unterschieden. Jüngere und allogen transplantierte Patienten wiesen hingegen eine teilweise deutlich eingeschränkte Lebensqualität im Vergleich zur Normalbevölkerung auf. Die im Rahmen der AMLCG99-Studie untersuchte Therapieintensivierung in der Induktionstherapie hatte keinen Einfluss auf die Lebensqualität der Patienten. Die Skala allgemeiner Gesundheitsstatus im QLQ-C30-Fragebogen misst vor allem körperliche Aspekte der Lebensqualität, da sie am besten mit der physischen Funktion und physischer Fatigue korreliert.