Podcasts about ajcc

Beyond the Digest are bonus episodes to the DermSurgery Digest that include reviews of interesting and relevant articles from JAMA Network and JAAD. Articles featured in this episode include: ·        “Oncologic outcomes for invasive squamous cell carcinoma with a clinically resolved biopsy site managed by watchful waiting: A retrospective cohort study” JAAD·        “Risk Factor Number and Recurrence, Metastasis, and Disease-Related Death in Cutaneous Squamous Cell Carcinoma” JAMA Network·        “A multicenter validation study of Mohs micrographic surgery versus wide local excision in primary high-stage cutaneous squamous cell carcinoma” JAAD·        “Identifying the impact of minor risk factors in Brigham and Women's Hospital stage T1 cutaneous squamous cell carcinomas on risk of poor outcomes: A retrospective cohort study” JAAD·        “Prevalence of poor outcomes in cutaneous squamous cell carcinoma by AJCC and BWH tumor stages: A systematic review and meta-analysis” JAAD·        “Lymphovascular invasion is an independent predictor of metastasis and disease-specific death in cutaneous squamous cell carcinoma: A multicenter retrospective study” JAAD·        “riSCC: A personalized risk model for the development of poor outcomes in cutaneous squamous cell carcinoma” JAAD  Beyond the Digest Contributors include Naomi Lawrence, MD, Dermatologic Surgery Digital Content Editor; Yesul Kim, MD, Beyond the Digest Co-host; Caresse Gamret, MD; Tara Jennings, MD; Sydney Proffer, MD; Yssra Soliman, MD; Kathryn Shahwan, MD; Ami Greene, MD; and. Your feedback is encouraged. Please contact communicationstaff@asds.net.

Your correspondent briefly muses on the difficulty of finding ways to improve when poker continually finds new ways to challenge and mislead you. He then reviews a $5/$10 session that featured some wild street-poker hands, including two in which he made huge folds.FORUM DISCUSSION: CLICK HERE0:15 On hunting for ways to get better6:48 $5/$10 NLHE session7:29 JJ on J65ddxThh9:03 AJcc on A75xddKx2x11:08 QQ on 962r5dd13:15 KK on J53rTr15:09 TT on 943rQcc8x17:01 $200 splash pot -- 99 on AK6rQdd4x20:12 QThh on T83rTr7x (including a discussion of the tactic of overlimping)25:24 AA on 863hhhKxJx34:08 JJ on KJ5ssxQx2xhttp://twitter.com/thirdwalkinghttp://crushlivepoker.com

Check out this episode on Bridges to Mental Health Workforce Expansion Project with Dr. Bill Lydiatt. The project is focused on expanding the capacity of primary care, specialty care physicians, APPs, nurses, social workers and others to increase their confidence and abilities in managing mild to moderate mental illness. https://clarksonregional.com/bridges-to-mental-health/ has more information on upcoming training dates and educational resources. Bill Lydiatt, MD is Professor of Surgery at Creighton University, Clinical Professor of Surgery UNMC, President of the American Head and Neck Society and Chair of the AJCC 9th Edition Head and Neck Staging panel and a member of the AJCC Editorial Board. He received his BS from Stanford University, MD and Otolaryngology Head and Neck Surgery Residency from University of Nebraska and fellowship in head and neck surgical oncology at Memorial Sloan Kettering Cancer Center in New York City. A former Chief Medical Officer and Vice President of Medical Affairs, VP of Surgical Services and Chair of Surgery at Nebraska Methodist Hospital, Lydiatt received his EMBA from the University of Colorado. We rely on your donations to keep producing this podcast content and to support physician advocacy in Nebraska. If you would like to support Nebraska Alliance for Physician Advocacy, a 501(c)(3) organization in Nebraska please click to DONATE NOW.    If you have questions or answers, please email us at contact@nebraskaallianceforphysicianadvocacy.org   Please check out our website at: Nebraska Alliance for Physician Advocacy Follow on social media: @NEAllianceforPhysicianAdvocacy on Instagram

El Dr. Luis Ubillos, oncólogo médico adscrito al Hospital Británico de Montevideo en Montevideo, Uruguay nos comentan sobre lo más destacado en melanoma presentado en el Congreso de ASCO 2024, resaltando los siguientes estudios: Enfermedad avanzada EBIN: estudio fase II, multicéntrico, abierto, aleatorizado, que evaluó si un enfoque secuencial con un período de inducción de 12 semanas con encorafenib + binimetinib seguido de inmunoterapia combinada con nivolumab + ipilimumab mejoró la supervivencia libre de progresión en comparación con la inmunoterapia combinada con nivolumab + ipilimumab solo, en pacientes con melanoma irresecable o metastásico con mutación BRAF V600. Enfermedad adyuvante COMBI-AD: estudio fase III, que evaluó el tratamiento adyuvante con dabrafenib más trametinib frente a placebo en pacientes con melanoma en estadio III (estadificación del AJCC) mutado con BRAF. Se incluyeron 438 pacientes en el grupo de tratamiento y 432 en el grupo de placebo, con seguimiento hasta por 12 meses o hasta recaída, toxicidad inaceptable, retiro de consentimiento o muerte. KEYNOTE-054: estudio fase III, doble ciego, que aleatorizó a pacientes con melanoma resecado en estadio III de alto riesgo. Este estudio informó los resultados del criterio de valoración exploratorio de la calidad de vida relacionada con la salud de pembrolizumab adyuvante vs. placebo. CheckMate-238: estudio fase III, aleatorizado, doble ciego de inmunoterapia adyuvante con nivolumab vs. ipilimumab después de la resección completa de melanoma en estadio IIIb/c o estadio IV en sujetos con alto riesgo de recurrencia Enfermedad neoadyuvante NADINA: estudio fase III, multicéntrico, que aleatorizó a pacientes con melanoma en estadio III nodal, macroscópico y resecable, que no habían recibido previamente inhibidores de puntos de control inmunitarios (ICI) o inhibidores de BRAF/MEK (BRAFi/MEKi), para recibir ipilimumab + nivolumab en neoadyuvancia seguido de disección terapéutica de ganglios linfáticos (TLND, por sus siglas en inglés). Análisis retrospectivo de SWOG S1801 en pacientes con melanoma en estadio clínico III tratados con nivolumab + ipilimumab en terapia neoadyuvante durante dos ciclos, seguido de cirugía y terapia adyuvante. Se aplicó la definición de supervivencia libre de eventos del estudio SWOG S1801.   Fecha de grabación: 11 de junio 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.

今週は中山競馬場でアメリカジョッキークラブカップ（芝2200m）が行われる。週末は雨予報が出ており、波乱の可能性も高い伝統の一戦だ。 ここでは、過去10年データからショウナンバシットとモリアーナにフォーカスした「75 o...The post 【AJCC／データ攻略】4歳馬2頭に「…

JRAは19日、第65回アメリカJCC（GII、芝2200m）の枠順を発表した。 数多の重賞を経験し抜群の安定感を誇るボッケリーニは8枠12番、晩成開花のチャックネイトは8枠11番、紅一点のモリアーナは3枠3番から発走す...The post 【AJCC／枠順】“単複回収値150超”12頭立てなら外…

今週は中山競馬場でアメリカジョッキークラブカップ（芝2200m）が行われる。過去にはブラストワンピースやアリストテレスといったGI好走馬も制したレース。今週末の雨予報を考えると、時計のかかる馬場への対応もカギとなりそうだ...The post 【AJCC／データ攻略】「穴党が…

21日にアメリカJCC（GII、中山芝2200m）を含めたWIN5対象レースが行われる。 JRAが指定する5つのレースで1着馬を当てるWIN5は、過去に5億円超えの高額配当を記録したこともある、まさに夢の馬券。先週は的中...The post 【AJCC／WIN5予想】モリアーナ“消し”　雨で好走気…

今週は中山競馬場で、第65回アメリカJCC（GII、芝2200m）が行われる。かつてはGI馬も参戦した伝統のレース。雨予報の今年は道悪適性も重要なファクターとなりそうだ。 ここでは馬券検討のヒントとして、出走馬12頭の全...The post 【AJCC／全頭診断】「2.5.1.0」条件合致の…

In this edition of Cancer Registry World, Elliot Asare, MD, FACS, discusses the role of cancer registry data in developing staging strategies for the 9th Version of the AJCC TNM system. Dr. Asare is a surgical oncologist and Assistant Professor at the University of Utah School of Medicine and Attending Surgeon at the Huntsman Cancer Center in Salt Lake City, Utah. In addition, Dr. Asare is the Chair of the AJCC Editorial Committee. Please enjoy listening and learning!

Clancy Krahn was crowned the new Jersey Queen in November, now you can meet her up close!

Your correspondent discusses the weird tension between cooperation and competition in the negotiations of ongoing straddles in cash games. He then reviews two recent midstakes cash game sessions. 0:55 On straddling9:05 5/5/10/(20) session no. 110:17 AA on AT7ddx6ddd14:47 99 all-in preflop18:06 KQo T65r6xT22:44 AJcc on 983xhh4xKx25:07 5/5/10/(20) session no. 225:15 64o on QQ7r4727:41 KTss T65r6x29:38 99 on J83r6ddJx31:02 AJo on AJ3ccxKdd8x32:00 KcKx on AT6ccc8x5x34:00 Some quick thoughts on double-board PLO bomb potsDisussion of this episode:CLICK HEREhttp://twitter.com/thirdwalkinghttp://crushlivepoker.com

In this JCO Article Insights episode, Emily Zabor summarizes two articles from the February 20th, 2023 Journal of Clinical Oncology issue: "Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study" by Johnson, et al  and "The POSEIDON Trial: Will Secondary End Points Change Our Clinical Practice?" by Remon, et al. The Original Report by Johnson, et al describes results of the Phase III POSEIDON clinical trial. The accompanying editorial by Remon, et al discusses the findings of a significant progression-free survival and overall survival benefit for the combination of tremelimumab plus durvalumab plus chemotherapy as compared to chemotherapy alone, which were secondary endpoints in the trial. TRANSCRIPT Emily Zabor: Welcome to JCO Article Insights for the February 20, 2023, issue of JCO. I'm your host, Emily Zabor, JCO Biostatistics Editorial Fellow.  Today, I will be providing summaries for two articles. The first article, titled ‘Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study,' by Dr. Melissa Johnson and colleagues, describes the results of the Phase III POSEIDON clinical trial. POSEIDON was a randomized Phase III clinical trial in patients with metastatic non-small cell lung cancer. The trial had a three-arm design to evaluate the efficacy of tremelimumab plus durvalumab plus chemotherapy; durvalumab plus chemotherapy; and chemotherapy alone in a first-line treatment setting. The two immunotherapies were selected for study because of their complementary mechanisms of action. Tremelimumab is an anti-CTLA-4 antibody which can diversify T-cell responses and lead to increased tumor infiltration. Durvalumab is an anti-PDL1 antibody which can enhance T-cell function. Chemotherapy is still an important treatment option for early disease control and potential for immune priming. Patients in the POSEIDON trial were randomized to the three arms with equal allocation. The co-primary endpoints for the trial were progression-free survival and overall survival for the comparison of durvalumab plus chemotherapy vs. chemotherapy alone. Then, a hierarchical multiple-testing procedure with a gatekeeping strategy was used across the primary endpoints and key secondary endpoints. Gatekeeping procedures are a way of controlling the type I error rate across multiple groups of null hypotheses that have a hierarchical structure, meaning that some of the hypotheses are considered more important than others. In this case, the plan was to first test for differences in progression-free survival and overall survival between the durvalumab plus chemotherapy and chemotherapy alone arms. Then, if either of those tests had a significant p-value so that the null hypothesis of no difference between groups was rejected, tests for differences in progression-free survival and overall survival between the tremelimumab plus durvalumab plus chemotherapy and chemotherapy alone arms would be conducted. Additional levels of testing could be conducted for other secondary endpoints following significance at the previous level. These types of gatekeeping procedures are a rigorous way of controlling the type I error of the entire study at 5% while still allowing multiple tests to possibly be conducted. The efficacy analyses were conducted in the intention-to-treat population, which included 338 patients on the tremelimumab plus durvalumab plus chemotherapy arm, 338 patients on the durvalumab plus chemotherapy arm, and 337 patients on chemotherapy alone. The median follow-up among those without an event was 10.3 months for progression-free survival and 34.9 months for overall survival. The findings for the co-primary endpoints were that progression-free survival was significantly improved with durvalumab plus chemotherapy versus chemotherapy alone, with 12-month progression-free survival rates of 24.4% versus 13.1%. There was no statistically significant difference in overall survival, with 24-month overall survival rates of 29.6% versus 22.1%.  Because progression-free survival was significantly different in the durvalumab plus chemotherapy versus chemotherapy alone arms comparison, according to the hierarchical testing procedure, the study proceeded to compare efficacy between the tremelimumab plus durvalumab plus chemotherapy and chemotherapy alone arms. Both progression-free survival and overall survival were significantly higher for the tremelimumab plus durvalumab plus chemotherapy arm, with 12-month progression-free survival rates of 26.6% versus 13.1% and 24-month overall survival rates of 32.9% versus 22.1%. The tremelimumab plus durvalumab plus chemotherapy arm had higher rates of grade III or IV treatment-related adverse events and immune-mediated adverse events as compared to the other two arms. The rates of grade III or IV treatment-related adverse events were 51.8%, 44.6%, and 44.4%, and the rates of immune-mediated adverse events were 33.6%, 19.2%, and 5.1% for the tremelimumab plus durvalumab plus chemotherapy; durvalumab plus chemotherapy; and chemotherapy alone arms, respectively.  This paper also reports on a number of subgroup analyses of overall survival comparing both the tremelimumab plus durvalumab plus chemotherapy and durvalumab plus chemotherapy arms to chemotherapy alone to examine consistency of effect across subgroups of patients. The results were found to be generally consistent across subgroups according to sex, age, tumor PD-L1 expression levels, histology, planned chemotherapy regimen, smoking history, race, ECOG Performance Status, and AJCC disease stage at diagnosis. Notably, patients with less than 1% PD-L1 tumor cells had no difference in hazard of death on durvalumab plus chemotherapy versus chemotherapy alone with a hazard ratio of 0.99, but had a reduced hazard of death on tremelimumab plus durvalumab plus chemotherapy versus chemotherapy alone with a hazard ratio of 0.77. But the study was not powered to conduct statistical tests for the subgroups, so no p-values are reported, and no strong conclusions can be drawn from the subgroup analyses.  Dr. Johnson and colleagues conclude that durvalumab plus chemotherapy significantly improved progression-free survival as compared to chemotherapy alone, and tremelimumab plus durvalumab plus chemotherapy significantly improved both progression-free survival and overall survival as compared to chemotherapy alone. The authors suggest that adding a limited course of tremelimumab to durvalumab and four cycles of chemotherapy provided long-term survival benefits to patients with metastatic non-small cell lung cancer and may represent a new first-line treatment option. The second article, titled ‘The POSEIDON Trial: Will Secondary End Points Change Our Clinical Practice?' by Dr. Jordi Remon and colleagues, is an editorial related to the first article just described. In the editorial, the authors discussed the findings of a significant progression-free survival and overall survival benefit for the combination of tremelimumab plus durvalumab plus chemotherapy as compared to chemotherapy alone, which were secondary endpoints in the trial. Recall that the POSEIDON trial had two co-primary endpoints of progression-free survival and overall survival for the comparison of durvalumab plus chemotherapy to chemotherapy alone, and the secondary endpoints were only evaluated since the co-primary endpoint of progression-free survival was found to be significant.  Dr. Remon and colleagues note that while there was no head-to-head comparison of the durvalumab plus chemotherapy and tremelimumab plus durvalumab plus chemotherapy arms, the tremelimumab plus durvalumab plus chemotherapy regimen had only a modest increase in progression-free survival and overall survival rates, but much higher rates of immune-related adverse events as compared to the durvalumab plus chemotherapy regimen. The authors suggest that following this trial, we still don't know what subset of patients would benefit from a dual immunotherapy treatment approach or what is the optimal duration of such treatment protocols. Recall that in POSEIDON, while efficacy was estimated in pre-planned subgroups, the study was not powered to detect effects within subgroups, so no statistical comparisons were made, and therefore no definitive conclusions could be drawn about whether a particular subgroup did or did not benefit from either of the experimental arms.  The authors point out that many combinations of immunotherapies have been studied for patients with advanced non-small cell lung cancer, and that there is likely little benefit from further studies where new drugs are added to current protocols in unselected patients. The authors emphasize that new predictive markers are urgently needed, especially given the financial toxicity associated with the use of immunotherapies. They propose that the study of such markers should be at the forefront of future trials. That concludes this episode on the articles ‘Durvalumab With or Without Tremelimumab in Combination with Chemotherapy as First Line Therapy for Metastatic Non-Small Cell Lung Cancer: Phase III POSEIDON Study', and the associated editorial, ‘The POSEIDON Trial: Will Secondary Endpoints Change Our Clinical Practice?'  Thank you for listening, and please tune in for the next episode of JCO Article Insights. 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.  Show Notes: Like, share and subscribe so you never miss an episode and leave a rating or review.   Articles Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study   The POSEIDON Trial: Will Secondary End Points Change Our Clinical Practice?   Find more articles from the February 20 issue.

See all the Healthcasts at https://www.biobalancehealth.com/healthcast-blog/ BioBalance Health® has always been on the cutting edge of the newest medical methodology available. In the fight against cancer, we are now using he newest genetic methodology to find cancers early, when they are treatable. Throughout my almost 40 years of practicing medicine, I have believed that medicine should embrace preventive care and be based on the belief that we should only react to a disease that is already established.  Now we finally have one test that screens for 72% of the cancers that we can't screen for.  It is hard to believe that  out of the 55 types of cancer we can only screen for  5 Cancers!   Medicine has only developed 5 screening tests that are currently in use to find cancers early.   Galleri is one simple blood test that screens for 50 types of cancer, to find them at early treatable stages, before they create symptoms, metastasize, or produce any symptoms. Galleri was created for those patients who have a positive family history of cancer, or those patients who are fearful of getting cancer of any type, and for those patients who have been successfully treated for cancer who want to find out early, if they have a recurrence!  Galleri It is the dream child of a company who has been testing and retesting it with the finest geneticists in the US. We are offering this test through our office as an option for those who need it to truly practice preventive medicine!  With Galleri, you have a good chance of being cured of cancer through very early detection! Before Galleri® was invented patients only had 5 cancers that could be detected early by screening tests.  The following list enumerates the 5 cancers we have screening tests for. Breast cancer: Mammography can find cancer after it has been growing for 11 years. Cervical Cancer: Pap and HPV Test only finds the virus and possibly the cells that might be cancer. Colorectal Cancer, Colon Cancer: Colonoscopy and stool tests Lung Cancer: Low Dose C-T Scan Prostate Cancer: PSA Test Routine screening tests are recommended because they have been proven to save lives by detecting some cancers earlier.3 The Galleri test does not preclude the use of the 5 screening tests that are currently in use, however there are more than 50 cancers that Galleri® can test for, and you receive your results in 10 working days. It is time to look at cancer more broadly, in addition to the 5 cancers that are routinely screened for today. The most important cancer is the one that you or your loved one may have — and curing cancer starts with knowing you have it! If cancer runs in your family, and you lose sleep worrying about it you should take the Galleri® Test.  If your genetic relatives (father mother, aunt or uncle, sisters or brothers or children have had cancer then testing yourself for cancer with Galleri® will answer the question as to whether you have it or not. Our patients at BioBalance Health® are offered this test yearly for high-risk patients and as needed, often less often than yearly.  The test is not covered by insurance as it is a new test…but can you wait until it is covered?   Worrying about cancer can make you literally sick by stimulating your adrenal gland's production of cortisol.  This worry impairs your immune system that protects you from cancer, putting you at higher risk! The only risk of Galleri® is the cost…$ 1,250 paid directly to the Galleri® company at the time of your blood draw.   50 Types of cancer detected by Galleri® The Galleri test is a multicancer early detection test that detects a common cancer signal across more than 50 types of cancer through a simple blood draw. A Adrenal Cortical Carcinoma Ampulla of Vater Anus Appendix, Carcinoma B Bile Ducts, Distal Bile Ducts, Intrahepatic Bile Ducts, Perihilar Bladder, Urinary Bone Breast C Cervix Colon and Rectum E Esophagus and Esophagogastric Junction G Gallbladder Gastrointestinal Stromal Tumor Gestational Trophoblastic Neoplasms K Kidney L Larynx Leukemia Liver Lung Lymphoma (Hodgkin and Non-Hodgkin) M Melanoma of the Skin Merkel Cell Carcinoma Mesothelioma, Malignant Pleural N Nasal Cavity and Paranasal Sinuses Nasopharynx Neuroendocrine Tumors of the Appendix Neuroendocrine Tumors of the Colon and Rectum Neuroendocrine Tumors of the Pancreas O Oral Cavity Oropharynx (HPV-Mediated, p16+) Oropharynx (p16-) and Hypopharynx Ovary, Fallopian Tube and Primary Peritoneum P Pancreas, exocrine Penis Plasma Cell Myeloma and Plasma Cell Disorders Prostate S Small Intestine Soft Tissue Sarcoma of the Abdomen and Thoracic Visceral Organs Soft Tissue Sarcoma of the Head and Neck Soft Tissue Sarcoma of the Retroperitoneum Soft Tissue Sarcoma of the Trunk and Extremities Soft Tissue Sarcoma Unusual Histologies and Sites Stomach T Testis U Ureter, Renal Pelvis Uterus, Carcinoma and Carcinosarcoma Uterus, Sarcoma V Vagina Vulva The Galleri test is intended to detect a cancer signal and predict cancer signal's origin to inform diagnostic evaluation. Cancer cases enrolled in CCGA Study1 were assigned a ​“cancer type” as defined in the American Joint Committee on Cancer (AJCC) manual (8th edition)2 (For this list of Cancer types detected, some of the names were modified/​edited to organize for easy reference). Cancer signals were detected across more than 50 AJCC-cancer types, which supports the potential for the Galleri test to detect a cancer signal over a diverse range of cancers across a wide biologic spectrum.  If you are a Biobalance Health® patient you can ask your Nurse Practitioner to make an appointment to have your blood drawn at our office.  The Galleri Test was created by GRAIL. 

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here.  Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting.   You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time.  Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space?  Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved.  So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade.  So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab.  And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years.  Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target.  So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot?  Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually.  And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit.  So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take.  And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here.  All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months.  Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim?  Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells.  And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators.  But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line.  So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years.  Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads?  Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after.  So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective.  They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist.  Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year.  Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3).  So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context?  Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells.  So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth.  And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore.  That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups.  So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years.  Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study.  So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout.  Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients.  Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk.  And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer.  So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma.  And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into  question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion.  And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery.  So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection.  Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about?  Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases.  And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells.  I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event.  And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late.  So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients.  Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses.  With that, thank you, Jason, for sharing your insights with us today.  Dr. Jason Luke: Thank you.  Dr. Diwakar Davar: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. So, thank you for your attention, and we will sign out.      Disclosures:  Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Vedanta Biosciences  Consulting or Advisory Role (Immediate family member): Shionogi  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences  Research Funding (Inst.): Zucero Therapeutics  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine  Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  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.     

This week's episode introduces us to the topic of melanoma We cover: - Risk factors- Precursor lesions- Histopathology and important histopathological features related to poor prognosis - Melanoma types and their appearance including superficial spreading, nodular, lentigo maligna melanoma, acral lentiginous, and desmoplastic - Workup including excisional biopsy and when to stage patients- Staging with AJCC 8th edition TNM staging classification - When to perform sentinel lymph node biopsy and lymph node dissection Keep an eye out for next week's episode where we talk about management of melanoma!DisclaimerThe information in this podcast is intended as a revision aid for the purposes of the General Surgery Fellowship Exam.This information is not to be considered to include any recommendations or medical advice by the author or publisher or any other person. The listener should conduct and rely upon their own independent analysis of the information in this document.The author provides no guarantees or assurances in relation to any connection between the content of this podcast and the general surgical fellowship exam.  No responsibility or liability is accepted by the author in relation to the performance of any person in the exam.  This podcast is not a substitute for candidates undertaking their own preparations for the exam.To the maximum extent permitted by law, no responsibility or liability is accepted by the author or publisher or any other person as to the adequacy, accuracy, correctness, completeness or reasonableness of this information, including any statements or information provided by third parties and reproduced or referred to in this document. To the maximum extent permitted by law, no responsibility for any errors in or omissions from this document, whether arising out of negligence or otherwise, is accepted.The information contained in this podcast has not been independently verified.© Amanda Nikolic 2022

Episode 15 of Derms and Conditions, has our host James Q. Del Rosso, DO speaking with Anthony Rossi, MD, a Mohs Surgeon at Memorial Sloan Kettering Cancer Center in New York City. First Dr. Rossi discusses the use of the AJCC and Brigham and Women's Hospital squamous cell carcinoma staging system. Next Dr. Del Rosso asks Dr. Rossi for tips on treating keratoacanthomas of the lower extremities with subcutaneous methotrexate. Finally, Dr. Rossi discusses the use of immunotherapy in treating squamous cell carcinoma.  

Dr. Stephen Liu, associate professor of medicine and director of Thoracic Oncology and Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, highlights key abstracts in lung cancer 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. Stephen Liu. He is an associate professor of medicine and the director of thoracic oncology and developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Liu joins me to highlight advances in lung cancer featured at the 2021 ASCO Annual Meeting. Dr. Liu has served in a consulting or advisory role for Genentech, Pfizer, and AstraZeneca, among other organizations. His full disclosures and those relating to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Liu, it's great to have you on the podcast today. Dr. Stephen Liu: Thanks for having me. ASCO Daily News: Dr. Liu, a lot of people were talking about the IMpower010 study during the annual meeting. That's abstract 8500, an interim analysis that showed really promising results for patients with resected non-small cell lung cancer. Can you tell us about this practice-changing study? Dr. Stephen Liu: Well, IMpower010 was a global randomized phase III trial, and I think this really was one of the highlights of the ASCO Annual Meeting from a lung cancer standpoint. As a reminder, our current standard of care is cisplatin-based chemotherapy for patients with resected stage II to III non-small cell lung cancer and for select patients with stage IB. We know from decades of experienced multiple phase III trials, large meta-analyses, that the risk of recurrence is quite high for resected stage II/III lung cancer. And the use of up to four cycles of cisplatin-based chemotherapy does lead to an improvement in survival, and that's our standard of care. That survival improvement, however, is modest, with an absolute improvement and 5-year survival of about 5%. And so we've been trying to improve outcomes in this setting for quite some time. We know from last year's ASCO that the subset of patients whose tumor harbors an EGFR mutation received some benefit from disease-free survival with the use of adjuvant osimertinib. IMpower010 presented at this year's ASCO by Dr. Heather Wakelee looks at the use of immunotherapy as a complementary adjuvant therapy. And we knew from press release that this study had met its primary endpoint. This was our first chance to look at the data first-hand and really see how it would impact practice. And I think the data were quite impressive. It's a fairly simple design. This study included patients with completely resected stage IB to IIIA non-small cell lung cancer, either histology. Note that this used AJCC version 7, and so the stage IB that were included had a size of at least four centimeters, and that's the subset that seems to derive the most benefit from chemotherapy. Now patients received cisplatin-based chemotherapy one to four cycles first. And those who received at least one cycle of chemotherapy were then randomly assigned 1 to 1 to receive 1 year of atezolizumab, PD-L1 inhibitor, or best supportive care. This was a large study, over 1,000 patients randomly assigned. It began enrollment in 2014. So it did include some EGFR and some ALK when maybe we didn't know quite as much about including those patients in these studies, but the EGFR was about 12%, the ALK was 3%. Some were unknown EGFR and ALK status, but these were likely the squamous histology, as those numbers line up. The PD-L1 testing, importantly, was done by the VENTANA SP263 assay, looking at tumor cell expression only, which is a fairly straightforward assay. And what we saw after a median follow up of almost 3 years was that in the primary high-risk population stage II to IIIA resected non-small cell lung cancer with the PD-L1 expression of at least 1%, the use of adjuvant atezolizumab significantly improved disease-free survival. And the hazard ratio there was 0.66. If we look at the 2-year disease-free survival (DFS) rate, it improved from 61% with best supportive care to 75%, and at 3-year DFS from 48% to 60%. So an improvement in the 3-year DFS rate and a hazard ratio of 0.66. The fourth plot showed that signal was greater in node-positive. As expected, no signal in that ALK subset, though it was small. But this is a pretty substantial improvement in disease-free survival. When we look at these Kaplan-Meier curves, they split immediately, really right at the first scan. And when we look at a study like this, this phase III trial, it reminds us how poor our current standard is; how many patients do suffer relapse and recurrence and death from this potentially curable cancer. Atezolizumab clearly improving outcomes in this subset. We then saw analyses of the resected stage II to III across PD-L1 strata, so positive and negative. And there the hazard ratio, as expected, less impressive, 0.79. If we look at the forest plot there, the hazard ratio for PD-L1 high, using that 50% cutoff we're used to, was substantial at 0.43. So overall, the DFS and PD-L1 positive 0.66 and the PD-L1 high 0.43. So no report on the PD-L1 low, which is what we're waiting for, that one at 49%, presumably not as impressive as 0.66. And we'll wait for those data to come out. But PD-L1 positive, a clear benefit. PD-L1 high, a substantial benefit. That's really where the formal analyses stopped. The stage IB to IIIA overall population was too immature for analysis, and overall survival was not yet formally tested. This will take a few years to breathe out. They did provide an early look at overall survival. And in that stage II to IIIA PD-L1 positive, there was the right trend, with a hazard ratio of 0.77, though not statistically significant. We did see these curves start to come apart at about 12 to 18 months, which is what you would expect if this study ultimately would lead out to be positive. We do want to wait for OS results. But one has to wonder, is a DFS benefit this substantial enough to change practice? And atezolizumab not yet approved in this setting, but the trial did meet its primary endpoint. And to me, for PD-L1 positive, and certainly for PD-L1 high, I do think these data aren't practice- changing. ASCO Daily News: Absolutely. Well, another trial that attracted a lot of attention was the CheckMate-816 trial. That's Abstract 8503. What can you tell us about the surgical outcome data reported in CheckMate-816? Dr. Stephen Liu: So CheckMate- 816 was a randomized phase III trial that looked at neoadjuvant therapy. So this also focused on resectable lung cancer. This is an area where we hope for cure, but for some of the more advanced stages, we don't necessarily expect it. Much room for improvement. We saw the IMpower010 data showing adjuvant immunotherapy improved DFS. Here we're looking at the neoadjuvant space. And at AACR in 2021, Dr. Patrick Forde presented some of the early PCR results. And that showed the pathologic complete response rates with neoadjuvant nivolumab plus chemotherapy for three cycles was superior to chemotherapy alone for three cycles. So the addition of nivolumab to chemotherapy improved the pathological CR rate from 2% to 24%. Really astounding. What Dr. Jonathan Spicer presented at ASCO 2021 were the surgical outcomes from that study. And we see that adding immunotherapy to chemotherapy significantly improves the pathologic CR rate. Does it come at a cost? Does it lead to more surgical complications? This is always a concern with neoadjuvant therapies. We've got someone in our clinic with a resectable lung cancer. If we mismanage that patient, we may lose the window for resection. So we always worry about delayed surgeries, canceled surgeries, more complicated surgeries. There have anecdotally been reports of increased perihilar fibrosis after neoadjuvant immunotherapy. Wouldn't that lead to longer, more complicated surgeries? And what we saw, frankly, was a bit surprising, for me. Surgery consistently easier, better in the experimental arm really across the board. The rates of going to surgery, completing surgery, 83% with nivolumab/chemotherapy, versus 75% with chemotherapy. So more patients going to surgery, fewer canceled surgeries. If we look at the type of surgery, minimally invasive surgery rates 30% with nivolumab/chemotherapy, [and] 22% with chemotherapy alone. Conversion to open thoracotomy was more common in the chemotherapy alone at 16%, the additional nivolumab 11%. And the complete R0 resection was achieved in 83% with nivolumab/chemotherapy, 78% with chemotherapy alone. Adverse events delayed surgery in six patients getting nivolumab and chemotherapy. It's important to watch that. But it was nine patients in getting chemotherapy alone. And if we look at the duration of surgery, and certainly there are many confounders in a statistic like this, but the surgery was shorter with nivolumab, certainly not lengthening the surgery. 184 minutes for nivolumab/chemotherapy, 217 [minutes] with chemotherapy alone. So these data are very reassuring to someone with a potentially resectable cancer. And I think that when I take a step back and look, maybe these results do make sense. Maybe this is what I should have expected. If we give a treatment that is more effective, that is a higher response rate, it works better. Those patients are less likely to have progressive disease, and the surgery should be more straightforward if there's less cancer to resect. So the CheckMate-816 surgical data, we've been waiting for this shoe to drop, and it was very reassuring. Perioperative immunotherapy is going to be an important part in the management of stage II/III non-small cell lung cancer in the years to come. Now going forward, we'll need to compare these adjuvant and neoadjuvant approaches and the relative merits of either strategy, but these results, I thought, were very reassuring. ASCO Daily News: Excellent. Well, moving on to the PACIFIC trial, Abstract 8511, this study reported improvements in 5-year overall survival and progression-free survival for unresectable stage III non-small cell lung cancer. What are your takeaways from this study? Dr. Stephen Liu: Sure. The PACIFIC study is a randomized phase III trial that's really set our standard of care for unresectable stage III locally advanced non-small cell lung cancer. This is a group where our standard of care, historically, has been concurrent chemoradiation, with the goal of cure, though, unfortunately, not necessarily the expectation, with recurrence rates quite high. We saw years ago the addition of 1 year of durvalumab improved progression-free survival, then ultimately improved overall survival compared to placebo. This was a fairly straightforward study. It enrolled unresectable stage III non--small cell lung cancer after chemoradiation, who did not have evidence of progression after completing therapy, to receive 1 year of durvalumab or placebo, a 2 to 1 randomization. The results markedly positive, leading to U.S. Food and Drug Administration (FDA) approval and really our new standard of care. These are long-term survival data, and it was presented by Dr. David Spigel. These are really important. Immunotherapy, the whole appeal of the strategy is the durability, the induction of memory T cells, meaningful long-term survival. Will this increase the rate of cure really is what we're going for. And when we saw the survival benefit with durvalumab, we knew that we were curing more patients. Long-term follow up is important to make sure that we don't have late recurrences, that we really are curing and not just delaying a recurrence for some patients. And in this analysis, with a 5-year follow up, we see durvalumab improve the median survival from 29 months with chemoradiation alone to 48 months with the addition of durvalumab. That's a hazard ratio of 0.72, 28% reduction in the risk of death, pretty substantial. That 5-year survival rate was 43% versus 33%. And importantly, these were very similar to the 4-year data that were presented by Dr. Corinne Faivre-Finn at World Conference in Lung Cancer, really very little drop off between year 4 and 5. And we refer to that as flattening of the tail, where the events are early, and at some point, they kind of stop happening. It's really what we want to see. While survival is what we hone in on, in an abstract like this, we also need to pay attention to progression-free survival (PFS). And the PFS rate at 5 years was 33% with durvalumab, versus 19% with chemoradiation alone. So 33% with no evidence of progression at 5 years. And if you are cured from lung cancer, then you can't have progression. So one in the three patients with no progression at 5 years, I think, is very reassuring, that PFS hazard ratio of 0.55. So prior to ASCO21, durvalumab was our standard of care. Now we just have longer term follow up to really solidify that choice. These are important data for patients and families to set expectations right, but our clear standard. Still, though, room for improvement in that 5-year PFS rate of 33%. We would like to see that higher, and ongoing strategies hopefully will help push that up. ASCO Daily News: Excellent. Some great survival data in the PACIFIC trial. Well, Abstract 9007 sparked a lot of interest as well. This is an expansion study of patritumab/deruxtecan in patients with EGFR-mutant non-small cell lung cancer. That's a difficult drug to pronounce, so I'm sure you'll do a better job. What can you tell us about this? Dr. Stephen Liu: Well, yeah, all these antibody drug conjugates do have tricky names, and so they are kind of fun to say. So patritumab/deruxtecan is a HER3 antibody drug conjugate. I suspect it will be better known as HER3-DXd, a little easier off the tongue. This was a study that looked at this agent in patients with EGFR-mutant non--small cell lung cancer after TKI therapy. And when we turn our attention to targeted agents, we have really transformative drugs with very wide therapeutic windows, little toxicity, very high efficacy, [and are] really game changers in patients with driver positive non--small cell lung cancer. But as we know, these treatments aren't cures. And we do expect resistance to osimertinib. The third generation TKI has been pretty heterogeneous. And once patients progress in osimertinib, the next standard therapy really is chemotherapy. And there's a bit of a drop off, with more toxicity, [and] less efficacy overall. So this remains an unmet need. Many studies are looking at different strategies there. We've seen the addition of MET inhibitors if MET is amplified for certain subtypes, RET, BRAF, for example, the addition of the targeted agents. This study, Abstract 9007 presented by Dr. Pasi Janne, looked at the HER3-DXd antibody drug conjugate. So patritumab/deruxtecan has a monoclonal antibody targeting HER3, a proprietary linker, and then a topoisomerase 1 warhead. And this was a phase I study that looked at 57 patients with EGFR-mutant lung cancer after TKI therapy mostly, but 90% were coming off of osimertinib. And what we saw, I thought, was very encouraging. This is a small, early study. These are very selective patients. But the response rate here almost 40%, disease control rate 72%, and the median progression-free survival with monotherapy of patritumab/deruxtecan was 8.2 months. These numbers may change as the studies get larger, but there's a clear signal of efficacy for patients who'd received chemotherapy before and then moved on to patritumab/deruxtecan. The response rate didn't really drop off, 37%. So even those that were more heavily pretreated, we're seeing a clear signal with response rates that really are higher than chemotherapy. What was, I think, most important, we saw efficacy of patritumab/deruxtecan across multiple different mechanisms of resistance. And so it wasn't one biomarker select. It really was active, very versatile agent. And really, I think that's what we need. While biomarker-driven resistance will be something we always hone in on and try to focus, we do need something that's much more versatile for rapid implementation. And this is having a lot of potential. [It was] very well tolerated. If we look at treatment-emergent adverse events, only one person stopped from a TEAE. Only 4% stopped due to TEAEs, so very well tolerated treatment. Response was also durable. One response listed was after 4 years of therapy, and so the potential for long-term disease control, long-term responses. So clearly an active drug. This is an area where we need a lot of drug development. Well tolerated, only 4% stopping due to adverse events and a nice signal of activity. Our next steps will be to make this a larger study to look in more patients to really hone in on the mechanisms and where this really is working. Can we widen that therapeutic index? And can we look at combinations? Is there a role to continue TKI with this, maybe for better CNS coverage or activity? That's what we'll see in the years to come. ASCO Daily News: Excellent. Well I'd like to ask you about a trial that you were involved in, the ARROW trial, Abstract 9089. Can you tell us about this impactful study? Dr. Stephen Liu: Yeah, sure. The ARROW trial is a study that I've been a co-investigator on for many years. This was presented by Dr. Giuseppe Curigliano. And this looks at a RET inhibitor called pralsetinib, originally when we first got involved called BLU-667. RET fusions are present in about 1% of non- small cell lung cancer. These are important events, because we know from other studies, such as the immunotarget registry led by Julien Mazieres,  that RET-positive lung cancers don't seem to respond as well to immunotherapy. However, in the past, the kinase inhibitors, the targeted agents we had the targeted RET, weren't very good. They had response rates around 30%, 40%, a lot of toxicity. These are drugs like vandetanib, cabozantinib. With the introduction of selective RET inhibitors, we've seen striking efficacy and much better tolerability. And we now have two approved RET inhibitors in this space--selpercatinib and pralsetinib--both receiving FDA accelerated approval based on their respective single arm studies. What we saw at ASCO 2021 from Dr. Curigliano was an update on the RET fusion positive lung cohort of ARROW. Again, this was a phase I/II trial looking at pralsetinib given at a dose of 400 milligrams by mouth once daily. We look at the patients with RET fusion-positive lung cancer. Now we just have longer follow up and more patients. And overall, the cohort exceeded 200 patients, so 216 patients for a pretty rare driver. And the response rate, 69%, very durable. The duration of response, 22 months. So really solidifying the efficacy and confirming the role in patients with RET fusion-positive lung cancer. If we break those data down a little bit, patients who had prior chemotherapy, which was 125 patients, response rate was 62%. The disease control rate, 91%. These responses are quick. The median time to responses is 1.8 months, so really that first scan. And that's what we see with targeted therapy. And we look at these waterfall plots, and I encourage you to take a peek at that. It's exactly what we want to see, the vast majority of patients, almost all patients, with some reduction and some with a quite substantial reduction. Again, the disease control rate after chemo was 91%. So really, the waterfall plot has that look that we seek for effective targeted therapy. The outcomes were even better in the first-line setting. Response rate originally 79% as first-line therapy. But the way the trial was originally written, it only included frontline patients who weren't eligible for chemotherapy for whatever reason. So that's going to be a more selective cohort. That was changed with an amendment. And once that was removed for people that were eligible for whatever frontline therapy you wanted to give, really our real world first line cohort, the response rate was 88%, disease control rate of 96%. So to think of a response rate in almost 90% of patients really gives us that confidence we want when we have a driver that we detect when we start a new agent. We're very confident that we're going to see efficacy in these drugs, very well tolerated, very few patients stopping due to a adverse event. A disease control rate of 96% in that first-line setting gives me the confidence to really use this in the first-line setting. ASCO Daily News: Absolutely. Well, as you know, the Annual Meeting this year focused on equity in cancer care. And there were a number of studies presented in the lung cancer space. I just wanted to get your thoughts on how this issue was addressed at the Annual Meeting in the lung cancer setting. I'm thinking of Abstract 9005 that looked at racial disparities. What are your thoughts on this issue? Dr. Stephen Liu: Yeah, this was an important abstract, I think. And the theme that Dr. Lori Pierce set of equity really was met by several different abstracts and was a recurrent focus for many important and really overdue discussions. Abstract 9005 was presented by Dr. Debora Bruno, and this really looked at disparities in biomarker testing. And we just talked about advances for EGFR-mutant lung cancer for RET fusion-positive non--mall cell lung cancer. We have many, many more, but we can only offer these agents if we know the target is present. And if we don't do proper biomarker testing, our care will not be optimal. If we don't know the molecular genotype of the cancer, we can't treat it properly. We are just guessing, and we're much more likely to deliver an ineffective therapy. We are potentially making subsequent therapies more dangerous. Knowing the right biomarker is critical to the proper management of non-small cell lung cancer. And if we don't have that, the outcomes will not be as good. The testing really is critical for the management of lung cancer. And what we saw from this abstract was there are disparities in how patients with non-small cell lung cancer are being tested, which simply isn't acceptable. This was a retrospective analysis that looked at Flatiron data, recent data, 2017 to 2020, a large data set, almost 15,000 patients with non-small cell lung cancer. Demographics were 66% white, 9% Black. If we look at biomarker testing specifically, patients who were Black were less likely to be tested, less likely to have proper biomarker testing, 73% versus 76%, less likely to have full next generation sequencing with a 10% difference, and less likely to get tested early. We know that testing really influences treatment from the jump right away. And if we don't have that information, our outcomes won't be as good. Our Black patients weren't being tested properly, weren't being tested in a timely manner. And more data showed that clinical trial participation was also decreased among Black patients, 4% involvement for white patients, 2% with Black patients. And these were actually very similar to what we saw in Abstract 9001 that was presented by Dr. Akinboro from the FDA. And that looked at patients who'd received chemoimmunotherapy. This was a pooled analysis looking at different PD-L1 cohorts. And what was noted on the demographics is that in the phase III registrational landmark studies, Black patients only represented about 2% of patients there as well. So strikingly similar numbers and a gross under-representation. It really is inexcusable and something we need to address. And we need to correct, because this is showing that our care is simply not up to par.  Trial participation is how we move the field, but many cases, especially in lung cancer, a field that moves so quickly, a clinical trial often represents the best possible option. And Black patients simply aren't enrolling in studies. And I think some of the disparities in clinical trial participation likely reflect some of the disparities in clinical trialists. And I think that if we continue to improve diversity in our workforce, in our oncology subspecialty, that'll be an important step into rectifying this. But this is something we need to look at critically. We need to assess all of our processes and think how we can do better today, and not tomorrow. ASCO Daily News: Absolutely. Thank you so much, Dr. Liu, for highlighting these really critical points and sharing your valuable insight on all of these impactful studies in lung cancer. Thank you so much. Dr. Stephen Liu: My pleasure. Thanks for having me. ASCO Daily News: And thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Stephen Liu Consulting or Advisory Role: Genentech, Pfizer, Lilly, Bristol-Myers Squibb, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Guardant Health, Janssen Oncology, MSD Oncology, Jazz Pharmaceuticals, Blueprint Medicines, Inivata, PharmaMar, Daiichi Sankyo/UCB Japan, BeiGene, Amgen, Turning Point Therapeutics, Elevation Oncology, and Novartis Research Funding (institution): Genentech/Roche, Pfizer, Bayer, Merck, AstraZeneca, Blueprint Medicines, Lilly, Rain Therapeutics, Alkermes, Bristol-Myers Squibb, Turning Point Therapeutics, RAPT, Merus, Elevation Oncology, and Erasca, Inc Travel, Accommodations, Expenses: AstraZeneca, Roche/Genentech, and MSD Oncology   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. John Sweetenham, associate director for clinical affairs at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and editor-in-chief of ASCO Daily News, discusses compelling approaches in cancer care featured at the 2021 ASCO Annual Meeting, including key studies on financial toxicity, drug prices, disparities in clinical trial accrual, and the impact of the COVID-19 pandemic on cancer screening.   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. John Sweetenham, associate director for clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center. Dr. Sweetenham also serves as editor-in-chief of ASCO Daily News. He joins me to discuss compelling approaches in cancer care featured at the ASCO Annual Meeting, including key studies on financial toxicity, trends in oncology drug revenue, disparities in clinical trial accrual, and the impact of the COVID-19 pandemic. Dr. Sweetenham reports no conflicts of interest relating to our discussion today. Full disclosures relating to all episodes of the podcast are available at asco.org/podcasts. Dr. Sweetenham, it's great to have you on the podcast again. Dr. John Sweetenham: Thanks, Geraldine. It's good to be here. ASCO Daily News: There's been a lot of interesting research on the impact of the COVID-19 pandemic on patients with cancer. Sadly, the pandemic caused the postponement or cancellation of countless screening procedures. Abstract 6501 looks at the impact of the pandemic on stage presentation of breast and colorectal cancers. What can you tell us about this study? Dr. John Sweetenham: I think this particular study is very important because it is a confirmatory study of observations that have been made in other environments. But in this case, it's a single institution study from UC San Diego. The implication, the basis of this study, obviously, is that screening programs have really been critical in reducing death rates from certain cancers. And breast and colorectal cancer would probably be the best examples of that. And as we know, during the pandemic, many people postponed or cancelled their screening procedures. And so there have naturally been concerns about what that will do to stage at presentation, and an anticipation that we will see more patients eventually showing up for our services with more advanced stage of disease. So in this study, the workers at UC San Diego looked at their patients who had been treated in the years 2019 and 2020. And the treating clinicians used stage at presentation, which was determined by standard AJCC staging modules pulled out of their electronic medical record. And they did a pretty straightforward comparison of the stage distribution for their patients between 2019 and 2020. And they focused especially on colorectal and breast cancer because those are diseases where screening is known to have a significant impact. The interesting data from this study are that the total number of new patient visits for cancer during 2019 and 2020 were actually remarkably similar. And if you look at the stage distribution across all cancer types and compare 2019 and 2020, there really isn't very much difference. But what's disturbing is that for patients with breast cancer, they observed a lower number of patients with stage I disease, which reduced from 64% in 2019 to 51% in 2020, and a higher number of patients presenting with stage IV disease, which went from 2% to 6%. And very similar trends were seen for the patients with colorectal cancer, where they saw a decline in stage I presentations and an increase in stage IV presentations. So these are, again, confirmatory data which highlight the problem with delayed screening. The investigators mentioned that they're going to continue to follow these numbers closely and are planning to present data from their experience in 2021 as well. I think that what this does is really--it emphasizes the need for us for ongoing efforts to encourage our patients to return to care, to return to their screenings, and frankly, to get vaccinated so that they will have more confidence in coming back and returning to care. ASCO Daily News: Thank you for sharing these data. There are a lot of financial toxicities associated with cancer care. And there's an interesting study, Abstract 6504, that uses data from patients' credit reports to measure the relative risk of adverse financial events in cancer patients after diagnosis compared to individuals without cancer. Can you tell us more about this? Dr. John Sweetenham: Yes. And my first disclaimer would be that I'm certainly not a health economist. But as someone who is a non-expert in this domain, I found this to be a very interesting study which looked at the relative risk of adverse financial events in patients with cancer compared with a control group. And it did this by using data that they pulled from the patient's credit reports, which, from my perspective, is a really interesting way of looking at the financial hardship. And the way they did this was they used the Western Washington SEER cancer registry for their cases who they investigated in this study. And they used the voter registry to identify their control patients or control cases, I should say. And then they used data from one of the credit reporting agencies to look for signals for what they describe as adverse financial events in the patients with cancer compared with the population. And they were able to identify levels of severity of adverse financial effects within this analysis. So to cut to the chase here, what's interesting is they identified more than 300,000 individuals, of whom just over 84,000 were patients with cancer. And the remaining 250,000 or so were control patients. And they looked at the available line of credit for these patients, and then also looked for signs of what they described as severe, or more severe, or most severe adverse financial effects. And the most severe would have been, for example, foreclosures on homes or repossessions of homes and properties. So obviously, pretty significant and very serious adverse financial effects. And if we just look overall at their results, so for example, severe adverse financial effects, there was a highly significant difference which demonstrated that these were significantly more common in the population of patients with cancer, the same being true for both the more severe and the most severe adverse effects. And so, in a way, you could argue not surprising. But I think it put some numbers around the fact that there are long lasting effects financially for our patients with cancer, for a significant proportion of them, as a direct consequence of their diagnosis and compared in quite a robust way against a non-cancer population. And these are real life and very long term consequences, so something that we just have to keep uppermost in our minds as we're planning the financial advice and the financial navigation that we provide to our patients during their cancer journey. ASCO Daily News: Absolutely. Well, let's focus on the price of cancer drugs. Abstract 6505 looks at trends in oncology drug revenue among the world's major pharmaceutical companies. The study's authors cite a 70% increase in the number of clinical trials for cancer drugs over the past decade, and a substantial increase in the price of cancer drugs. In fact, the study found a 96% increase in sales revenue from cancer drugs among the world's top pharmaceutical companies over the past decade. So what are your thoughts about this? And why, in your opinion, is this study important? Dr. John Sweetenham: Thanks, Geraldine. Yes, I think that this study is important on a number of levels. I think when one first looks at the results of this study, it would be easy to conclude that, well, this is just one more piece of data that shows that the cost of cancer drugs is rising and is too high. And that's reflected in the extraordinary financial toxicity that we see in our patients with cancer. And you know, I think that there are elements of that which are probably true. But I do think there are other interesting observations from this. For example, as you mentioned, they demonstrated that sales revenue from cancer drugs has increased by more than 96%. And interestingly, revenues from non-cancer drugs among the same companies have actually decreased during that time. I would also mention, because it may be relevant, that although the analysis primarily included true antineoplastic drugs, they did include a number of supportive care drugs in this analysis as well, which are primarily used in patients with cancer. And so, certainly, I think in addition to the antineoplastic drugs, probably, the supportive care drugs have been part of the driver of this increase in revenue. The other interesting part of this is that during the study period, oncology revenues have grown, whereas revenues for other non-oncology drugs across all of the companies involved have remained stagnant. So what can we draw from this? First of all, as I said, I think the message about the cost of drugs is familiar to all of us and is not a new one. I think it is very interesting that there's been a 70% increase in the number of clinical trials of cancer drugs. And I think what that's telling us is that clearly, there has been enormous activity and substantial opportunity for the development of new cancer drugs. So as we look at these numbers, I think one of the positive spins to put on this is the fact that there are a lot more anti-cancer drugs coming online, a lot more trial activity. And in the long run, I think that has to be good for our patients. And we should be, to some extent, reassured by the fact that there are so many more drugs. I think also, what's interesting, although I certainly wouldn't editorialize over this, is the fact that this apparent explosion in activity and revenue around anti-cancer drugs has apparently been at the relative disadvantage of patients with other diseases, not really a thing for us to comment on that from what I classify as an editorial perspective. But I think the message for us and for our patients from this study is mixed, that, yes, there does seem to be some imbalance in terms of the amount of revenue generated out of these drugs. On the other hand, there are many of these agents now in clinical trials and on the market that weren't there a number of years ago. And overall, I think that that indicates the positive side of this story. ASCO Daily News: Well, I'd like to address a very important and timely topic, access to care. Abstract 100 reports the outcomes of a 5-year initiative of community outreach and engagement to improve enrollment of adult Black patients in clinical trials. How would you assess this initiative? Dr. John Sweetenham: I think this initiative and the results that they've produced really underlines, more than anything else, number one, the complexity that is involved in addressing this issue and the sort of multifaceted approach one has to minority accrual. And secondly, it underlines to me that there's no quick readout. One has to wait a while to see the effects of this kind of intervention. And there have been successful attempts to improve minority accrual to clinical trials. There are many ongoing initiatives. What struck me as being interested about this study from the University of Pennsylvania was the kind of multi-pronged approach they took to this. So they report that in 2014, Black residents comprised 19% of their population, [and] 16% of the cancer cases seen in the Philadelphia area. But only 11% of patients at the Abramson Cancer Center at the University of Pennsylvania were Black. And the number of Black participants who were recruited onto their treatment and interventional studies were relatively low, ranging between 8% and 13%, depending upon the type of study. So they developed a center-wide program with a number of key elements, which included tailored marketing. They had plans within each individual protocol for how they were going to enroll African American patients. They developed partnerships with faith-based organizations and conducted educational events. They provided Lyft and Ride Health to address transportation barriers. They had patient education by nurse navigators and an improved informed consent process. So they really approached this addressing several of the factors that play into the disparity in clinical trials accrual. And what they found is after 4 to 5 years of taking this approach, the percentage of Black patients seen at their center had increased to 16.2 from 11.1. And when they looked at the percentages of African American patients who they accrued onto their trials, it was really quite substantially increased. So if you remember, prior to this intervention, the range was from 8% to 13%. At the conclusion of this study, the rate was from 22% to 33%. So they had seen a 1.7 to 4-fold increase in 5 years. So I think that this persistent multi-pronged approach addressing many of the factors that play into these disparities was really interesting. And it demonstrates that to really make a significant impact on some of these disparities requires a lot of work over a long period of time. And as I said, the readout may not come immediately. It takes a while for the effects to truly be seen. ASCO Daily News: Exactly. Some great approaches there for people to look at in Abstract 100. Well, my final question relates to concerns from health insurers, that clinical trial participation can increase the total cost of care for patients. So in this study, Abstract 6513, investigators looked at the impact of clinical trial participation on total costs paid by Medicare during the oncology care model program in a large community-based practice. Can you tell us more about this study? Dr. John Sweetenham: Yes. This is an interesting study which is based on patients enrolled into the oncology care model. For those who may not be aware of this model, it's an alternative payment model which has been developed by the Centers for Medicare and Medicaid Innovation to address improvements in quality of care, as well as address issues of cost of care for patients with cancer. This study is based out of the community-based practice of 90 oncologists who practice [at] over about 30 sites of care. And what they did in this study was to link trial data and electronic medical record data with data generated from the oncology care model for patients undergoing treatment for various cancers between 2016 and 2018. And important to point out that the OCM includes patients who are Medicare beneficiaries only, so represents patients over age 65. And what they were trying to address in this study was whether the entry of patients onto clinical trials actually results in increased costs, which is, I think, some of the sort of received wisdom that's out there, that clinical trials are expensive. The OCM provides a slightly more controlled environment in which to study that and find out whether costs of care associated with clinical trials actually do overall increase the cost of care, something which clearly will be of great interest to insurers. So in addition to exploring this from the perspective of antineoplastic treatment, the group also had the opportunity to look at some non-trial episodes, and in particular, study the impact of the receipt of active treatments in the last 14 days of life as well as hospice use and hospitalizations. So these are other kind of issues which are important to us now which the OCM provides a window on. So the study was conducted and included just over 8,000 OCM episodes which met criteria for the study. And of those, 459 of the episodes included patients who were on a clinical trial. And interestingly enough, on average, episodes when the patient were on a clinical trial cost almost $6,000 less than matched non-trial episodes. And it was independent of whether it was an early phase or a late phase study. And interestingly, but perhaps not surprisingly, the primary reason for these lower costs was because of the increased drug costs. Because typically, the cost of the drug would have been covered by the trial. Interestingly, there were no differences in the rates of treatment within the last 14 days for the patients who were on the study. And there was no difference in rates of hospitalization or hospice use for the patients who were on the studies either. So the take-home message from the study was that the inclusion of patients in a clinical trial actually, overall, led to a reduction in Medicare costs for Medicare beneficiaries. And so it didn't support the concern that many third party payers have, that entry of their covered patients onto clinical trials actually cost more. Just one possible note of caution is that this was a community oncology-based practice. And it's possible that the breakout of patients on early phase versus late phase clinical trials might have been very different from what we might encounter in a more academic oncology setting. But nevertheless, I found this to be an important study which, to some extent, explodes a misconception that putting patients on studies costs a lot more money. ASCO Daily News: Absolutely. Well, Dr. Sweetenham, thanks for highlighting some really interesting studies on a range of very important issues impacting the cancer care community. Dr. John Sweetenham: Thanks, Geraldine, a pleasure as always. 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. John Sweetenham: 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.

Marieke van der Noordaa, PhD kandidaat in het Antoni van Leeuwenhoek te Amsterdam, onderzocht de aanvullende prognostische waarde van de residual cancer burden (RCB) en Neo-Bioscore op de conventionele AJCC-stadiëring. In deze podcast bespreekt zij met prof. dr. ir. Koos van der Hoeven de resultaten van een studie waarin patiënten die neoadjuvante chemotherapie hebben gekregen zijn onder te verdelen in subgroepen met ieder een andere prognose.

本日の「ながら競馬ニュース」です。忙しいあなたの代わりに競馬に関するニュースをピックアップして音声でお届けします。#アブドゥラ殿下の死去後も事業継続 #アドマイヤザーゲしまいを生かす競馬で若駒Ｓ #アリストテレスが始動どれだけ絞れるかAJCC

HOPA Now is the official podcast of the Hematology/Oncology/Pharmacy Association, an organization dedicated to supporting pharmacy practitioners and promoting the advancement of Hematology/Oncology/Pharmacy to optimize the care of individuals impacted by cancer.   These educational podcasts are part of our BCOP Preparatory and Recertification Course, which is designed to prepare oncology pharmacists preparing to sit for the BCOP Certification Exam, as well as meet the BPS requirement to complete a BCOP Preparatory/Recertification Review Course.   In this episode of HOPA Now, Dr. Neelam Patel details the epidemiology, pathophysiology, and staging of breast cancer, one of the most commonly diagnosed cancers in American women. She offers data, diagnosis percentages, and survival rates for breast cancer patients; shares common risk factors, presentation, and common histologies of breast cancer; and details prognostic factors and recent changes to adjuvant treatment guidelines.   In this episode you will learn:   Breast Cancer Fundamentals Data, diagnosis percentages, and survival rates surrounding breast cancer Common germline mutations in breast cancer patients Risk factors regarding breast cancer, including gender, family history, and estrogen exposure Common presentation of breast cancer masses and common histologies of breast cancer Tumor size, nodal status, and presence of metastatic disease and other prognostic factors including ER/PR and HER2 status and grade of tumors Recent changes to adjuvant treatment guidelines   Mentioned in This Episode: HOPA   Quotes:   “Breast cancer masses usually present as a painless lump that is self-detected or found on screening mammograms.” — Dr. Neelam Patel   “In recent years the AJCC updated their guidelines to include other prognostic factors such as ER/PR and HER2 status and grade of the tumor.” — Dr. Neelam Patel   “One thing to remember is this is a prognostic stage and is more to help the clinician and patient understand what their prognosis is, and does not necessarily dictate treatment.” — Dr. Neelam Patel  

The American Joint Committee on Cancer along with the International Union for Cancer Care have long supported the use of a standard language to define patients with cancer. The 7th and 8th editions of the AJCC-UICC staging systems have now been adopted and function to improve eye cancer research and clinical care. The major ophthalmic journals now require its use for research publications as to allow them to be compared and or combined in multivariate analysis. The largest ophthalmic societies now expect both tumor and patient staging in presentation. Clearly, the use of AJCC-UICC tumor staging has brought ophthalmic oncology into the mainstream of world-wide cancer care.

An interview with Dr. Jessica Geiger from Cleveland Clinic on “Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline.” This guideline provides evidence-based recommendations addressing diagnosis, surgery, radiation therapy, and systemic therapy for patients with squamous cell carcinoma of unknown primary in the head and neck. Read the full guideline at www.asco.org/head-neck-cancer-guidelines.   Transcript [MUSIC PLAYING] 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] Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jessica Geiger from Cleveland Clinic, author on Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck ASCO guideline. Thank you for being here, Dr. Geiger. Thanks, Brittany, for the invitation and the opportunity. First, can you tell our listeners what is squamous cell carcinoma of unknown primary in the head and neck and what this guideline generally covers? Sure. So cancer of unknown primary or carcinoma of unknown primary in the head and neck is metastatic squamous cell carcinoma found in cervical lymph nodes. And importantly, there's a lack of a primary mucosal tumor that's identified. So these patients comprise about 5% of all head and neck cancers. And it poses a challenge for all members of the treatment team, both from a diagnostic perspective but as well as treatment management; what is the best way to proceed for treatment with these patients? Now this guideline provides an up-to-date and evidence-based management for recommendations. And these recommendations are based on published literature. But where the data is lacking in the literature, expert panel consensus was utilized to provide recommendations. I'd like to discuss some of the key recommendations of this guideline. First, with regard to diagnosis of squamous cell carcinoma of unknown primary in the head and neck, what are the challenges, and what are the recommendations from the guideline? The diagnostic challenges come about when a patient presents with a neck mass. They often have imaging, a clinical exam. But again, about 3 to 5 percent of patients, we will be unable to locate where this tumor started. Squamous cells don't show up in the lymph nodes by themselves. They came from somewhere else. And part of the reason that this makes a diagnostic challenge if we're not able to readily see where the primary tumor is, oftentimes, it's very small in size. And so it's not picked up by imaging or by a physical exam. Also, these are sometimes difficult anatomic locations to evaluate. So all of this can pose a challenge to coming up with the right diagnosis. Now some of the recommendations for diagnosing these patients, obviously, we need to have a complete history and physical exam. And this physical exam should include a fiberoptic laryngoscopy, so a good lab endoscopy exam looking at all of the mucosal tissues, trying to find abnormalities, trying to see where exactly this cancer started. Now in order to make the diagnosis of squamous cell carcinoma, obviously, a biopsy needs to be done, and that is in the neck, where these suspicious nodes are. Either a fine needle aspiration or a core needle biopsy is recommended within these guidelines. The guidelines also indicate when to do additional pathologic testing. So this is for high-risk HPV, especially in neck nodes that are in level two or three. If high risk HPV testing is negative, then we give recommendations regarding Epstein-Barr virus testing, so looking to find is this nasopharynx primary cancer and then, of course, imaging guidelines. So the image modality of choice is a contrast enhanced CT of the neck, not just to elucidate and better evaluate the nodal burden of disease, which the patient presents with, but also to investigate for evidence of a mucosal primary. Now if that fails to produce a primary then we give recommendations regarding PET scans. And then what are the recommendations for surgery for a squamous cell carcinoma of unknown primary in the head and neck? There are many recommendations that we go into to address the surgical approach to a cancer with unknown primary. Now the previous question asked about diagnosis included in the surgical recommendations in our guidelines for diagnostic surgical interventions. So we can sort of branch point or divide recommendations for surgery, whether it's a diagnostic or a therapeutic procedure. And then in the therapeutic procedures, we can look more in detail at what surgery is recommended for a primary or the mucosal, and then how to how do we address the neck? So first, as part of diagnosis with surgery, all patients need a complete operative evaluation of the upper aerodigestive path. And this includes directed biopsies. So the surgeon goes in the operating room, gets a good look around. Any suspicion for any possible cancer is biopsied, as opposed to blind biopsies or random biopsies, which are not recommended. Now the recommendations for surgery also include when to do tonsillectomies and what tonsillectomies to do. So are these palatine tonsillectomies or lingual tonsillectomies? Do we perform them or recommend them on the ipsilateral side, or what is the role for a contralateral or even bilateral tonsillectomy? And I won't go into the specifics because they're all-- all the different scenarios are laid out within the guidelines, but the recommendations are based on the patient's nodal burden. So do they have bilateral lymph nodes; do they have lymph nodes just on one side; how big they are, that all plays a role into the recommendations regarding surgical intervention. Now if mucosal primary tumor is identified, there are clear recommendations and guidelines that every effort to clear the disease with negative margin is of paramount importance. So we're talking about a definitive oncologic surgery in this case. And the reason we want to stress that negative margins are the goal is because we're trying to avoid trimodal therapy. So we're trying to get to a good surgical resection. A positive margin left behind is likely going to lead to recommendations for postoperative radiation with the addition of radiosensitizing chemotherapy, which is what we do not want. We want to try to avoid toxicities with trimodal therapy. That brings me to then surgical management of the neck and the guidelines set forth in this document. So recommendations for neck surgical management are broken into whether the patient has what we consider small volume disease versus large volume disease. So for small volume disease, small lymph nodes on one side of the neck, we recommend a multidisciplinary discussion whether or not the patient should be best served with a definitive surgery involving a neck dissection or if they should have definitive radiotherapy. Again, our goal is to avoid trimodal therapy. So if there's obvious gross extranodal extension seen on imaging, then they would be best served with a primary radiation approach, as opposed to surgical. Similarly, any large volume disease, obviously, gross extranodal or extracapsular extension, definitive chemo radiotherapy is favored. Now a comment on management of the neck, if you're suspecting an oropharynx primary, which is the majority of cancer of unknown primaries of the head and neck, we give specific recommendations regarding what levels to routinely surgically dissect, levels IIa, III, and IV in that instance. In your discussion of the surgical recommendations, you began to touch on the radiation recommendations. Could you elaborate on those recommendations from ASCO on radiation therapy for this patient population? Of course. And again, when you refer back to the guideline and the recommendations, there are even more specific recommendations regarding when and how to use primary radiotherapy or adjuvant radiotherapy in this setting. So I'm not going to go into great detail for every single recommendation that is provided, but a nice overview is, basically, if a patient is receiving radiotherapy as the primary definitive management of cancer of unknown primary, obviously, we recommend treatment should be given to gross nodal disease but also to neck regions and mucosal anatomic regions, which are considered at risk for containing microscopic disease. So it's not just good enough to radiate what we see on imaging but also to consider the areas around it, the nodal echelons and other mucosal areas where there could be cancer. So for example, an HPV-related disease where it's likely oropharynx unilateral disease, there are specific locations to include. And this is also the same for HPV-negative disease. Now if we're worried about a possible nasopharynx cancer in the setting of E-Barr or EBV-positive disease, the mucosal radiotherapy can be limited to just the nasopharynx, but you want to radiate bilateral necks, level II through IV, and include the retropharyngeal lymph nodes. There are specific recommendations where unilateral versus bilateral neck irradiation is recommended. And again, I just encourage the listeners to refer back to the guideline itself for these specific instances. Also included within the radiotherapy guidelines and recommendations are specific doses. What doses do you use? Where do you use these doses? And these doses are extrapolated from known and well established evidence for traditional head and neck squamous cell carcinoma in which we know where the primary is, also, when to give post neck dissection kind of in the adjuvant setting, again, all extrapolated from known head and neck squamous cell carcinoma but very specific and laid out within the guidelines. And what does the expert panel recommend for systemic therapy for squamous cell carcinoma of unknown primary in the head and neck? Similarly, when we devised the recommendations for radiotherapy for this disease, the use of systemic therapy, when to use it, when to add it to radiation is also extrapolated from the head and neck guidelines and evidence for known head and neck cancer. So we recommend adding chemotherapy to definitive radiotherapy in advanced nodal disease, and we've defined what advanced nodal disease is based on the AJCC 8th Edition. So in HPV-negative disease, this is N2 or N3, in HPV-positive disease, multiple ipsilateral lymph nodes. If a lymph node is greater than three centimeters, we recommend adding chemotherapy to radiation in the definitive setting. Now, specifically, the chemotherapy that we recommend is cisplatin. Again, this is based on well-established studies and evidence in head and neck cancer. So patients who are medically fit and able to receive cisplatin, that is the treatment of choice. There are also recommendations regarding resected cancer of unknown primary. So with evidence of extranodal capsular extension, we recommend the addition of, again, cisplatin chemotherapy to postoperative radiotherapy, again, extrapolated from well-established head and neck studies. And then, again, if you are concerned that this is an Epstein-Barr-related nasopharynx cancer, stages II through IVA, again, AJCC 8th Edition, we recommend the addition of chemotherapy to radiation in those settings as well. Great. This guideline covers a lot of ground and many recommendations. Can you speak to why this guideline is important and how you envision it will impact practice? So this guideline is important because a fair amount of patients will be presenting with cancer of unknown primary. We stress through this guideline that this is very evidence-based recommendations and guidelines with a focus on a multidisciplinary approach to how to treat these patients. And finally, how will these guideline recommendations affect patients? Well, hopefully, this guideline will provide reassurance to patients that no matter where they are receiving treatment, they are receiving quality standard of care management, again, largely driven by evidence. And it doesn't matter whether they're treated by locally practicing experts and specialists or at a large institution, they're being treated by the standard of care that is accepted across the board. Well, thank you for your time today, Dr. Geiger, and for working on these comprehensive guidelines. You're very welcome. Thanks, Brittany. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/head-neck-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available and iTunes or the Google Play Store. If you have enjoyed what you've heard today, please write and review the podcast and be sure to subscribe so you never miss an episode.  

本編 日経新春杯と住み分けがイマイチ出来てるのか謎の重賞AJCCです！ 少頭数ですが、頑張って当てちゃいますよ～。 明日はオフ会もあるので景気付けにしたいです！！ コーナー紹介 ※新コーナー始まりました！！！！ 「グルー...

In this podcast, Katie Houselog, a certified oncology nurse practitioner with Minnesota Oncology, presented at Ridgeview Medical Center's Live Friday CME Series on October 11, 2019.  At this event, updates to metastatic breast cancer was provided. Enjoy the podcast! OBJECTIVES:    Upon completion of this podcast, participants should be able to: Define metastatic breast cancer, AJCC staging, and prognostic indicators. Identify the subtypes of metastatic breast cancer. Discuss evidence-based national guidelines (NCCN). Describe the side effects of breast cancer treatment. Summarize how symptoms are monitored and managed. Identify and recommend available breast cancer resources. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org.   CLICK ON THE FOLLOWING LINK FOR YOUR CME CREDIT: CME Evaluation: "2019 Metastatic Breast Cancer Update" (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.   FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: SUMMARY 1: Metastatic breast cancer.  Three words that most people don't really ever want to hear. But what is happening now with the care of our patients who are surviving with this diagnosis. Metastatic breast cancer affects about 155,000 Americans. Up to 10% are diagnosed with stage 4, meaning it has spread well outside the breast, to various organs and lymph nodes. Unfortunately even in women who attend their regular mammograms, it may not be detected. 20-30% who initially had earlier stage disease will recur. Young women can be diagnosed, as well as men. Breast cancer type is important to distinguish, and its important to note that the diagnosis of metastatic disease is not necessarily a death sentence. The NCCN (National Comprehensive Cancer Network) provides guidelines for the care of the various types of breast cancer.  Speaking of the types of breast cancer, this can be confusing. There is ER, or estrogen receptor positive and HER2 (or human epidermal growth factor) + or -.  In addition, there is also PR or progesterone receptor + or -.  The majority however have estrogen receptor + and HER2 - breast cancer.  The more + receptors present, the more treatment options there are.  Triple negative disease tends to have the worst prognosis (Estrogen, HER2, and Progesterone receptor negative_. There is some promise on the horizon for treatment of this, but the situation still is not great. The 5-year prognosis is just under 30% for metastatic disease sufferers. The same breast cancer drugs are used regardless of where the tumor has metastasized to.  Locations of disease progression varies, and can include the liver, lungs, bones and brain, to name a few. SUMMARY 2: Treatment options have significantly improved over the years. Hormonal therapy, and the CDK46 inhibitor, which was approved a few years ago, as an example. Targeted immunotherapy is also being used, especially in triple negative cancer.  Radiation therapy is used for metastatic breast cancer to help prevent local recurrence or for bone involvement and pain.  Supportive care, such as palliation and hospice is also important. There are a lot of chemotherapeutics, and these can be confusing to the primary care provider and other front line clinicians. Hormonal therapy is give for estrogen receptor + cancer; early stage breast cancer as well.  Selective estrogen receptor modulators such as tamoxifen, are used in pre- and post-menopause.  Other oral drugs that block estrogen receptors include aromatase inhibitors such as letrozole. LH/RH antagonists, such as Lupron and Zolodex, shut-down the pituitary-gonadal axis. Oophorectomy is also sometimes performed. Estrogen down regulators, such as Fluvestrant, are also used. The CDK46 inhibitors however now stretch out the time to progression of the disease to 27-months from what used to be about a year. Fortunately no significant side effects are seen with this, but neutropenia can happen, although rarely neutropenic fever. Therefore, treatment is continued despite neutropenia with this particular class of drug.  If compliance is an issue, the injectable Fluvestrant is preferred over a CDK46 inhibitor. In women with significant metastases, some up front cytotoxic chemotherapy will sometimes also need to be started in estrogen + patients, followed by hormone therapy.  In general, though chemo and endocrinologic therapy is not combined.  This is per the ASCO (American Society of Clinical Oncology) guidelines. SUMMARY 3: Patient "LT" was diagnosed with early breast CA, stage one. T1C, NO  MO. She was hormone receptor + times 2 and HER2 -.  She was treated with chemotherapy, then tamoxifen and zoledronic acid to prevent osteoporosis. Six years later, she presented with dyspnea.  She had significant liver mets. Her CA2729 was markedly elevated.  By rights, she should not have recurred.  A re-biopsy confirmed the same initial cancer.  A CDK46 inhibitor with hormone therapy was given. To prevent fracture in the setting of bone mets, zoledronic acid or denosumab are given.  Rarely, osteonecrosis of the jaw can happen with this type of drug. HER2 + disease represents about 1/3 of patients.  The backbone of therapy for this is Herceptin or trasztuzamab.  Herceptin and pertuzamab, along with chemotherapy will be given for a newly diagnosed HER2 + case, then a short while later, the chemo will be dropped.  For brain metastases, lapatinib with xeloda can be given as well.  Cardiac function can be affected by Herceptin and these patients must be followed by cardiology.  In the setting of estrogen and HER2 + disease, often a combination of hormonal and HER2 directed therapy used.  Sometimes chemotherapy is given first.  Although not usual at the same time as the other two.  Herceptin and hormonal therapy can be used simultaneously, though. Immunotherapy, specifically atezolizumab with a chemotherapeutic agent is indicated for metastatic breast cancer, which appears to extend lifespan to 25 months, versus 17 months of chemotherapy alone.  This is specifically for triple negative breast cancer.  They do need to be PDL 1 +, however, in order to be treated with this.  This is tested for through tumor pathology. Another case, a 19 yo female was diagnosed with metastatic breast CA.  She was estrogen + and HER2 -.  She went through treatment initially with chemotherapy, then recurred a few years later, and on this recurrence a repeat biopsy result was different.  She is not triple -.  She was started on chemo and atezolizumab.  Her follow-up PET scan showed a + response within about 6 mos. Immunotherapy is used in a lot of different cancers now: renal, bladder, melanoma, and others.  These drugs are check-point inhibitors, which essentially engage out T cells to destroy the cancer cells.  In general, some of the more common chemotherapy side effects are not seen with immunotherapy.  However, immune side effects can be seen, such as hepatitis, colitis, and thyroiditis.  These side effects are treated with a prolonged steroid course.  Pembrolizumab can be used in MMR deficient cells, or mismatch repair deficient cancer cells and microsatellite instability high disease (in other words, cells that are prone to mutate).  It shows some real promise in women who have previously been treated with other therapies for their cancer and those have been exhausted. SUMMARY 4: BRAC (or B-R-C-A mutations), can be seen in breast, ovarian and fallopian tube cancers. The platin therapies show good results in this group.  Genetic testing and counseling is important for women with breast cancer.  As in the case discussed, a woman with significant metastatic disease involving the liver, there was a pseudocirrhosis type clinical picture and the patient demonstrated marked improvement in her liver function and ascites and overall quality of life. PARP inhibitors are given to help prevent repair of the DNA destruction that happens due to chemotherapy drugs. Essentially, preventing reformation of cancerous cells.  These drugs in addition to standard therapy demonstrate improved survival as well. Next generation sequencing is important as well as it looks at the molecular biology, essentially what attributes a particular type of breast cancer has, and allows us to more adequately target with the various treatment modalities that are available or on the horizon.  One downside, however, is that we may be able to pick up mutations that we don't yet have a treatment for. Monitoring for breast cancer is not purely by the book.  There are subjective reasons for monitoring as well, and becomes individualized depending on symptoms, type of disease, cancer marker lab trends as well as response to treatment.  Imaging intervals and type of imaging is also somewhat dependent on the patient for these reasons as well. Breast cancer patients are living longer, and we need to continue to help them an empower them to live as high a quality of life as possible.  Various conferences and organizations exist that help our patients continue to cope with and survive their cancer.  But, there is also help out there for significant others, friends, and family members who are supporting their loved ones through this difficult time in their life. CONCLUSION:A special thanks to Katie  for joining us and for all the work she does to help patients suffering with breast cancer.  It's important work, and research is ongoing to hopefully one day put an end to this disease.  But until then, Katie and others like her continue to take excellent care of these patients by providing them with meaningful treatment as well as hope for a cancer free future!

This JCO Podcast provides observations and commentary on the JCO article, "Treatment of Childhood Nasopharyngeal Carcinoma with Induction Chemotherapy and Concomitant Chemoradiotherapy: Results of the Children’s Oncology Group ARAR0331 Study" by Rodriguez-Galindo et al. My name is Suzanne Wolden, and I am the Director of Pediatric Radiation Oncology at Memorial Sloan Kettering in New York City, USA.  My oncologic specialty is Pediatric Radiation Oncology. This important manuscript summarizes the results of Children’s Oncology Group protocol ARAR0331 for childhood nasopharyngeal carcinoma.  The study enrolled 111 patients, of whom 75% were male and 47% were African American, with a median age of 15.  Eligible patients had AJCC stage IIb-IVC disease and received three cycles of induction chemotherapy with 5-fluorouracil and cisplatin followed by concurrent cisplatin and radiotherapy.  Three patients had progressive disease during induction chemotherapy, eight were removed from the study due to physician or parent preference, and another three were not evaluable.  This left 97 patients evaluable for response and concurrent chemoradiotherapy.  Responses and radiotherapy treatment plans were not centrally reviewed but were left to the judgement of the treating institution.  All patients received 45 Gy to comprehensive head and neck fields encompassing the nasopharynx and bilateral level I-V lymph nodes.  A boost to the nasopharynx and residual gross nodal disease was prescribed based on response.  The full dose of 70.2 Gy indicated for stable disease was given to 18.6% of patients while 77.3% received the protocol specified dose for complete or partial response of 61.2 Gy or lower.  Another 4.1% of patients received intermediate non-protocol doses of 63.9-66.6 Gy.  The trial was amended to reduce the cycles of concurrent cisplatin during radiotherapy to two from three after unacceptable rates of renal and gastrointestinal toxicities were reported.    This trial was limited to patients age 18 years and younger and consisted primarily of American patients.  It is notable that the demographics of nasopharynx cancer in these young patients differ significantly from adults with this diagnosis.  Most patients are teens since nasopharynx cancer is vanishingly rare in younger children.  The majority were male, and nearly half were African-American.  Nasopharynx cancer is quite rare in teens of Asian descent, in stark contrast to the adult population.  In international series, it has been noted that teens in countries around the Mediterranean also have a relatively high incidence of this rare cancer.  The study illustrates that pediatric patients are much more likely than adults to have advanced disease and WHO type III, Epstein Barr virus-associated histology. Despite a lack of central review, the response rate appears to be quite high to induction therapy as one might expect with WHO type III carcinoma.  It is surprising that any patients had progressive disease, and I suspect that the rate of partial and complete response may have been even higher than what is inferred from the radiation boost doses given.  Nonetheless, the strategy of induction therapy was highly successful in allowing a large majority of patients to receive reduced doses of radiation.  It is important to note that all patients received 45 Gy to initial comprehensive fields rather than the 50 Gy typically used for adults and that smaller, more forgiving fractions of 1.8 Gy were used in comparison to the standard 2 Gy for adult head and neck cancer.  While some patients received a standard adult boost dose of 70.2 Gy, 81.4% received a lower boost dose.  In most cases, this was the protocol specified 61.2 Gy, a 13% dose reduction.  Even with these significantly lower doses, local control was exceptionally high, with only 5.5% of patients experiencing local failure with or without a distant relapse. The successful reduction in radiotherapy doses in this study is incredibly important and by far the most newsworthy aspect of this paper.  Even full or nearly grown teens experience dramatically more severe late effects of radiotherapy compared to older adults.  The severity of soft tissue fibrosis 10 or more years after full doses of radiation to the head and neck is so great that many patients require feeding tubes and tracheostomies.  The rate of second malignancy is also much higher in young patients.  The rate of distant relapse of 10.5% was low, considering that patients with metastatic disease at diagnosis were enrolled.  It is possible that with more advanced staging scans such as FDG-PET, metastatic lesions can be more easily detected and defined.  In that case, they can be targeted with radiotherapy to decrease the risk of relapse.  This approach has been shown to be effective in achieving cure in adults.  It is unlikely that an increase in chemotherapy beyond what was used in this protocol would be tolerated or worth the added toxicity.  Indeed, it is unclear whether the 3rd cycle of concurrent cisplatin was beneficial since there was only a trend for improved EFS and the cumulative toxicity is significant.  One must be mindful that increases in systemic therapy have been shown to decrease tolerance for head and neck radiotherapy.  This can be counterproductive to outcome if there are delays, breaks or failure to complete the course of radiation. This trial was so successful in its ability to decrease radiation exposure in young patients, that we should be inspired to go further.  My thoughts regarding the next trial would be to use PET scans for staging and response assessment and to push the radiotherapy doses lower.  This approach is currently being investigated for adult HPV associated head and neck cancer with doses as low as 30 Gy.  Perhaps in pediatric (or even EBV positive adult) nasopharynx cancer, 30-36 Gy would be enough for the comprehensive initial fields with boost doses in the range of 50-60 Gy for those who respond favorably to induction chemotherapy.  Dose reductions of this magnitude would make major differences in the acute and especially the late toxicities.  In addition, modern radiation technologies such as proton therapy allow improved avoidance of normal tissue exposure for these young, curable patients. In summary, this article provides evidence that response-based radiation dose reduction is possible for pediatric nasopharynx cancer.  Even with numerous limitations, the outstanding results of this trial inspire us to continue moving forward in the direction of reducing radiation exposure for these young patients.  Long-term follow up is also urged to quantify the expected benefits of these therapeutic changes. This concludes this JCO Podcast.  Thank you for listening.

Dr. Greene and Dr. Pawlik will discuss the 8th edition of the TNM staging system for pancreas and hepatobiliary cancers, which affirms that the anatomic extent of disease remains the strongest predictor of outcome in hepatobiliary cancers. Dr. Pawlik is ASO Deputy Editor and Editorial Board Section Editor, Hepatobiliary Tumors. He is co-author with Yun Shin Chun and Jean-Nicolas Vauthey of the ASO TNM staging editorial, "8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers." Dr. Pawlik’s primary clinical interests include alimentary tract surgery, with a special interest in hepatic, pancreatic, and biliary diseases. He is a member of the Johns Hopkins’ Miller-Coulson Academy of Clinical Excellence, in recognition of consummate clinical excellence in his field. Dr. Pawlik is Chair of The Ohio State University Wexner Medical Center’s Department of Surgery, as well as The Urban Meyer III and Shelley Meyer Chair for Cancer Research.

Dr. Greene and Dr. Edge will discuss the TNM staging system and its relevance to breast cancer management. Dr. Edge was Editor-in-Chief of the 7th Edition of the AJCC Cancer Staging Manual published in 2009 and co-author with Armando E. Giuliano and Gabriel N. Hortobagyi of the ASO editorial, “Eighth Edition of the AJCC Cancer Staging Manual: Breast Cancer” Dr. Edge is the Vice President for Healthcare Outcomes Policy and Professor of Oncology at the Roswell Park Cancer Institute. Dr. Edge also serves as Immediate Past Chair of the Commission on Cancer, on the Cancer Support Community Policy Institute of the National Advisory Board.

TRANSCRIPT An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines 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. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion."  Thank you for being here today, Dr. Adelstein. Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion. First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers. And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease. And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years. What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients. There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy. The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment. First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification? Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before. Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used. But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available. Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent. And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation. All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary. And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this. So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer. The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent. So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed. So what are the provisional clinical opinions that were made by the expert panel? They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7. Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension. And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial. Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards. And finally, how will this guidance affect patients? So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered. I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good. Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein. And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr. Greene and Dr. Gershenwald discuss the 8th edition of the TNM staging system for melanoma, and its use for communication between physicians and their patients as well as its impact on decision-making and prognostic assessment. Dr. Gershenwald is co-author with Richard A. Scolyer of the ASO TNM staging editorial, “Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond.” Dr. Gershenwald is a surgical oncologist-investigator in melanoma, with a research focus on integrating clinical, pathological, molecular and immune factors to improve melanoma staging and to develop clinical tools to improve clinical decision-making for patients with melanoma. Dr. Gershenwald is the Dr. John M. Skibber Professor of Surgery, Department of Surgical Oncology, and Medical Director, Melanoma and Skin Center, The University of Texas MD Anderson Cancer Center, Houston, and Chair, American Joint Committee on Cancer (AJCC) Melanoma Expert Panel.

Dr. Greene and Dr. Byrd discuss the 8th edition of the TNM staging system, which through its advances supports the concept of a team approach to cancer staging by clinical oncologists including cancer registrars, pathologists, and radiologists. Dr. Byrd is co-author with Dr. Greene of the ASO TNM staging editorial, “The Eighth Edition of TNM: Implications for the Surgical Oncologist.” Dr. Byrd is the Chair of the American Joint Committee on Cancer (AJCC) and his clinical expertise includes surgical oncology, endocrine neoplasms (thyroid, parathyroid, adrenal), breast cancer, melanoma, and Merkel cell carcinoma. Dr. Byrd is Professor of Surgery and the Section Chief of Surgical Oncology at the University of Washington.

An interview with Dr. David Adelstein of the Cleveland Clinic on the ASCO PCO which provides statements on the role of treatment deintensification in the management of p16+ oropharyngeal cancer. Read the full PCO at www.asco.org/head-neck-cancer-guidelines 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. David Adelstein from the Cleveland Clinic Taussig Cancer Institute. Lead author on "Role of Treatment Deintensification in the Management of p16 Positive Oropharyngeal Cancer: ASCO Provisional Clinical Opinion."  Thank you for being here today, Dr. Adelstein. Thank you, Shannon. Before we get started, I'd like to first note the contributions of my panel co-chair, Drew Ridge, and those of all of the other panel members. And I'd like to extend a special thank you to ASCO for their support in allowing us to put this together and specifically Nofisat Ismaila who did a tremendous amount of work in allowing us to complete this provisional clinical opinion. First, can you give us an overview of the clinical issue for this PCO? Sure. So this really came out of the implications of human papillomavirus mediated oropharynx cancer. I think as most of the listeners know, over the last several decades we've recognized the fact that oropharynx cancer has a second ideology, that not all of it is caused by tobacco use, but that the human papillomavirus is now the major ideologic factor in North American and northern Europe. The importance of this is that the human papillomavirus-induced oropharynx cancer is a different disease. It has a number of different characteristics from the kinds of head and neck cancer we've seen in the past. It's a disease that tends to occur in younger patients, patients who are otherwise generally more healthy. It is unassociated with smoking, although it can occur in smokers. But it's much more frequent in nonsmokers. And I think most importantly, it's a disease that has a dramatically better prognosis than the tobacco related disease. Now over the last several decades, our ability to treat advanced head and neck cancer has improved significantly, because we've begun to incorporate non-operative treatments-- chemotherapy and radiation-- and have been more aggressive in our utilization of chemotherapy and radiation with significantly greater success than we had in the past. The problem with this kind of treatment is that it is quite rigorous. And there's a good deal of acute and, more importantly, late toxicity that patients experience from these kinds of approaches. Now as we became more familiar with the importance of HPV associated oropharynx cancer, we realized that there are subgroups of these patients who have cure rates that are in excess of 90%. And the question arose whether the kinds of rigorous chemotherapy and radiation therapy treatments that we were utilizing were really necessary. Was it necessary to cause this much acute and late toxicity in patients who in vast majority of cases were going to be cured of the disease. And it's important, because these are younger patients. And the late toxicities are going to have a major impact on their quality of life for a number of years. What came about was the notion of treatment deintensification, the idea that perhaps it would be possible to deintensify the kinds of treatments we were giving in select patients. It's a very compelling hypothesis for medical oncologists and radiation oncologists. But there are a number of problems as we try to test this hypothesis. The first problem is how do we identify the good risk patients? There are patients with HPV-positive disease who do not do so well-- the heavy smokers and patients with very advanced tumors. And we need to be careful if we're going to be talking about giving less treatment that we don't give less treatment to the patients who have a worse prognosis. We pick the best prognosis patients. There have been a number of what we call risk stratification schemes that have been developed looking at trying to identify the very good prognosis patients-- those patients who are HPV positive who don't smoke and who have relatively limited disease extent. There's not universal agreement on how best to define these patients. All we know is that they do exist, that you can look at patients with these characteristics and see very good outcomes. One of the issues that has come up is how do we utilize the American Joint Committee staging system-- AJCC the 8th edition. One of the things that AJCC 8 did which is new is that it defined a separate staging system for patients with HPV-positive oropharynx cancer, a system which is entirely different than the staging system that we've used for head and neck cancers for many years. This was based on the recognition that the prognosis of patients with HPV-positive disease is so good so that many patients who we would previously have considered to have stage 4 disease are now classified as having stage 1 tumors, because their prognosis is so good. And that can be confusing, because the typical thought process for an oncologist is that a patient with stage 1 disease should be treated with single modality therapy. The reason that the HPV-positive patients have such a good prognosis, however, is that many of them have been treated with combined modality therapies. And to make the assumption that because now they're classified as stage 1 is incorrect. It is they shouldn't be treated with less intensive treatments and can be confusing. AJCC 8th edition is a prognostic robust staging system, but it really doesn't help us in defining treatment. First problem is how best to define patients who are appropriate for deintensification. Second problem is, what do you do to deintensify? What constitutes meaningful deintensification? Well, over the last 10 or 20 years there have been some significant advances in our standard treatments for all head and neck cancers that weren't developed the idea of deintensification. We now have tremendous experience using transoral surgical techniques, which are generally minimally morbid, much less morbid than the former open techniques that previously were used, which allows consideration of surgery for many of these patients where we wouldn't have considered it before. Similarly, intensity modulated radiation therapy has been widely adopted, and d clearly an approach using radiation, which is far less difficult, far less toxic than the former 2D or 3D radiation planning techniques that used to be used. But if we talk about intensification, what kinds of things can we do to deintensify our treatments? Well, one thought is to reduce the radiation dose. Then the question is, how much reduction is reasonable? And how much reduction is going to actually impact on this toxicity? And are our toxicity measuring tools adequate to even detect the difference in reduction of a radiation dose? Many of our toxicity tools are very crude. Perhaps we should be using some of the patient-reported outcome quality of life instruments that are available. Other thoughts are, perhaps one can reduce the size of the radiation therapy field. Can we reduce the dose of the chemotherapy? Can we eliminate chemotherapy? Can we even use less intensive chemotherapy? Generally, the other treatments for this disease have employed high doses of cisplatin, which is a toxic agent. And then there the question has been asked as to whether we can reincorporate minimally morbid transoral surgical techniques in an effort to better pathologically stage patients and define more appropriate adjuvant treatment. Perhaps not all patients need adjuvant radiation or chemotherapy and radiation. All of these approaches are interesting. They're exciting. They're being tested. But all of the experiences is preliminary. And that really brings us to the third and the biggest problem in any deintensification approach. And that's the need to be certain that if we deintensify our therapy, we're not going to compromise outcomes. It would not be acceptable to give less treatment or less intensive treatment if our survival were compromised. And we have to be certain that we don't do this. So what has evolved over the past decade is a whole number of treatment approaches that have some very enthusiastic early results. But these are generally single arm phase 2 reports where there is no comparison to conventional treatment. And they become difficult to interpret, because the results in general are very good. I think what really raised a red flag for us and that really caused us to take notice was the results of the RTOG 1016 trial that we reported last year. And at the same time, the European de-escalate trial, both of which had a similar design. These were studies that were designed in an effort to see if treatment deintensification would be possible by randomly comparing the standard treatment radiation and cisplatin with what was felt to be a less intensive approach-- radiation and concurrent cetuximab. And cetuximab is an accepted agent in the United States for treating head and neck cancer. The assumption here is that the survival would be equivalent when these two arms were compared, but that the toxicity would be improved by giving the less intensive systemic agent-- the cetuximab. The surprise when the study was analyzed was that that assumption was incorrect, that the radiation and cetuximab arm-- the deintensified arm-- actually proved inferior in terms of survival. And this was in both trials-- both the RTOG trial and the trial from Europe. And that was a big note of caution, because it was somewhat unexpected. I think we learned from that kind of a study, from a good randomized-- a large randomized trial-- that even though the outcomes may appear to be good, we need to be very careful about deintensifying our treatment until we're sure that the survival is equivalent. So although it's tempting for the clinician to see these very exciting reports about administering less treatment with the idea of producing less toxicity, the guideline advisory committee for ASCO really thought it was important that we get the message out that this kind of approach is not a treatment standard. This remains an investigational approach, and that the treatment standards for this disease really haven't changed. So what are the provisional clinical opinions that were made by the expert panel? They made several statements. The first was to acknowledge that the idea of treatment deintensification is a very compelling hypothesis, and it does require careful and appropriate testing. The second was that even though we are now better at identifying good prognosis patients, and we've seen some very promising early results, and even though we're now reclassifying patients with previously advanced stage HPV-positive disease as stage 1 or stage 2 tumors, the treatment recommendations for this disease have not changed. And they're based on the results achieved using AJCC 6 and 7. Standard of non-operated management to patients who are eligible to receive cisplatin remains high concurrent radiation and high dose cisplatin given every three weeks. If patients undergoing a surgical resection, then adjuvant chemotherapy and radiation with radiation and high dose cisplatin every three weeks is recommended in those patients with high risk factors of positive surgical margins or external tumor extension. And most importantly, deintensification, though it's a compelling hypothesis, is something that should only be undertaken on a clinical trial. Why is this guidance so important? And how will it affect practice? Well, I think the important thing about this guideline is that it shouldn't affect practice. The practice shouldn't change. The standards of care are not altered. And that for the clinician, this remains something that is exciting, something that should encourage enrollment on a clinical trial, but that we haven't changed treatment standards. And finally, how will this guidance affect patients? So from a patient's point of view, I think there is continued reason for optimism. A patient with the diagnosis of an HPV-positive oropharynx cancer is a patient with a very good prognosis. Patients are increasingly sophisticated. They read about the potential for treatment deintensification, and recognize that this is not something which is an accepted standard. But it should encourage their participation in clinical trials if [INAUDIBLE] is offered. I think ultimately it's a remarkable thing when oncologists can consider the possibility of reducing treatment intensity because the treatment results have been so good. Great. Thank you for your overview of this PCO. And thank you for your time today, Dr. Adelstein. And thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full PCO, go to www.asco.org/head-neck-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr. Jayanthi Vijayakumar, oncologist with the Minnesota Oncology & Ridgeview cancer and Infusion Center, discusses renal cancer, including differentiating renal cancer from other forms of cancer, and evidence-based national guidelines used in the treatment of renal cancer. Objectives: Upon completion of this CME event, program participants will be able to: Differentiate kidney cancer from other cancer types. Understand and describe AJCC staging in clinical practice. Identify appropriate prognostic indicators. Identify evidence-based national guidelines (NCC) used in treatment of kidney cancer. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit:  CME Evaluation: Metastatic Renal Cell Cancer Management - CME Enduring Activity (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.”   FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event.

On today's show we focus on melanoma and welcome Dr. Mark Faries onto the podcast. We discuss his role in the MSLT-I and MSLT-II trials as well as how their results have influenced the most recent editions of the NCCN and AJCC clinical practice guidelines. Before jumping into our interview with Dr. Faries, we take some time to introduce the basic staging principles for melanoma and the highlights of the MSLT-I and MSLT-II trials. 0-12:00 - Brad and Alston give overview of melanoma workup and 8th edition AJCC staging. Brief intro to MSLTI and MSLTII. 12:00- Interview with Dr. Faries 

This enduring CME will expire on 10/3/2020. The presentation is originating from Northeast Georgia Medical Center Gainesville, in the Auxiliary Conference Room. Target Audience: All physicians and allied health professionals. Activity Objectives: Upon completion of this activity participants should be able to: 1.  Verbalize the role of the managing physician in cancer staging. 2. Integrate information based on patient history & physical examination findings accurately supplemented by imaging intraoperative findings and pathologic data to stage cancer cases. 3. Recognize the challenges TNM staging system in clinical practice. Disclosures: - There is no commercial support for this activity - The CME planning team members have disclosed that there are no relevant personal or financial relationships Accreditation and Designation: The Northeast Georgia Medical Center & Health System, Inc. is accredited by the Medical Association of Georgia to provide continuing medical education for physicians. The Northeast Georgia Medical Center & Health System, Inc. designates this live activity for a maximum of 1 AMA PRA Category 1 Credit(s) TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

On this episode of SO Files, Alston, Brad and Linda take a closer look at the recently published TAILORx Clinical Trial Published in NEJM by Sparano and colleagues. The study expands the existing clinical application of the Oncotype DX score. If that score sounds familiar its because it has been making its way into clinical practice over the past few years (see our last episode on the new AJCC guidelines!). We explain the origin of the score, how it has been incorporated into clinical practice thus far, and how this trial addresses a large gap in the existing literature.

On this episode of SO Files, Brad and Linda cover the updated staging guidelines for breast cancer that have been in practice (theoretically) since Jan 1, 2018. The possibilities for stage groups now cover a full six pages in the AJCC manual and you can hear Brad and Linda read through each one right here.... just kidding. We will however cover the major changes, the reasoning behind them, and talk about how they are fitting into practice with podcast favorite Dr. Cyr. Show Breakdown: 0-14 minutes: Background information with Brad, Linda and Alston 14 minutes- end: Brad and Linda interview Dr. Cyr

America’s Job Center of California (AJCC) is your easy one-stop access to the state’s employment-related services. In this episode you'll discover how to get the most out of your AJCC and tips for a successful job search. 

From the SDPA 14th Annual Fall Dermatology Conference 2016, held November 3 – 6 in Las Vegas, Nevada. Topic: Melanoma/Cutaneous Oncology Update Faculty: David Hymans, MD Learning Objectives: 1.) Understand the AJCC staging of malignant melanoma and the implications of such staging for management of melanoma. Limitations of current clinical [...]

Interview with Julie Ann Sosa, MD MA, author of Rethinking the Current American Joint Committee on Cancer TNM Staging System for Medullary Thyroid Cancer

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, covers what surgery for pancreatic cancer entails, what the recovery process is like, and the importance of surgeon experience in outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, discusses the factors that determine whether a person's pancreatic cancer is resectable and the importance of this factor in predicting clinical outcomes.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, reviews the general concept of cancer staging, the basic workup and staging of pancreatic cancer, and the implications of this process on treatment recommendations.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, reviews the general concept of cancer staging, the basic workup and staging of pancreatic cancer, and the implications of this process on treatment recommendations.

Dr. Matthew Katz, surgeon at MD Anderson Cancer Center, reviews the general concept of cancer staging, the basic workup and staging of pancreatic cancer, and the implications of this process on treatment recommendations.