Podcasts about iiib

JCO Editorial Fellow Dr. Ece Cali Daylan and JCO Associate Editor Dr. Thomas Stinchcombe discuss the ASCO 2025 Simultaneous Publication paper "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small-Cell Lung Cancer." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Ece Cali: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Ece Cali, JCO Editorial Fellow, and I am joined by JCO Associate Editor, Dr. Tom Stinchcombe. In this episode, we will discuss the Journal of Clinical Oncology article and abstract presentation "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer.” NeoADAURA is a randomized global phase III study investigating the efficacy of neoadjuvant osimertinib-containing regimens in patients with resectable EGFR-mutated stage II to IIIB non–small-cell lung cancer. 358 patients were randomized 1:1:1 to receive osimertinib plus chemotherapy, osimertinib monotherapy, or placebo plus chemotherapy in the neoadjuvant setting. The primary endpoint was major pathological response. Osimertinib plus chemotherapy and osimertinib alone demonstrated MPR rates of 26% and 25%, respectively, compared to 2% in the chemotherapy plus placebo arm with a p-value of less than 0.001. Tom, can you please explain to our listeners how you interpret this data? Dr. Thomas Stinchcombe: Great question. Yeah, I think to give a little context, obviously, chemotherapy and immunotherapies preoperatively is becoming the standard of care. However, patients with EGFR-mutant lung cancer generally have not responded to immunotherapy, and many of the trials excluded patients with known EGFR mutation. There have been smaller phase II trials that had looked at EGFR TKIs preoperatively, but none of these were definitive. So I think that this trial is a big trial, and I think some of the strengths are that it has osimertinib alone and chemotherapy with osimertinib arms as compared to the standard of chemotherapy. I think it's going to be really interesting at the meeting to see how this is discussed by the discussant and also what the reaction is to its public presentation. And I think that's largely because there's an alternative paradigm now, surgical resection adjuvant osimertinib, that's available to patients. So I think this will be interesting to see what the reaction is to the induction therapy. For patients with known N2 disease, I've generally given some form of induction therapy prior to surgical resection. So I think that's the subgroup of patients that I'm most likely to employ this approach with based on the results. Dr. Ece Cali: So, in this trial, more than 90% of the patients on the osimertinib-containing regimens underwent curative-intent surgery. So, this speaks to the feasibility of the approach, and the higher MPR rate with osimertinib-containing regimens is encouraging. Event-free survival data is currently immature. You have already touched upon some of the strengths of the trial, but what are the weaknesses and the strengths of this trial? Dr. Thomas Stinchcombe: So, I mean, I think there are some weaknesses. A major pathological response was chosen as an endpoint, and there could be an argument that path CR is more of a prognostic marker. However, the rates of path CR are relatively low, so it would have been very hard to design a trial such as that. And then I think the trial started off as a preoperative trial but effectively became a perioperative trial with preoperative EGFR-TKI, postoperative osimertinib. And so I think it's going to be very hard to determine what the contribution of the components are. And then you've hit on another part that I think is very important when we interpret the data that the maturity on the event-free survival is only 15%, and most people are still on therapy. So the event-free survival, which is an important endpoint, is very immature right now. Dr. Ece Cali: And this trial was designed to compare the neoadjuvant approaches, hence the comparator arm here is neoadjuvant chemotherapy followed by surgery. So, considering the ADAURA trial results with upfront surgery followed by osimertinib as adjuvant, so how do you see this trial's impact on the current clinical practice? Dr. Thomas Stinchcombe: Well, very good question, I think one that we're still struggling with as we kind of look at this data. I think, for me, stage II patients will most likely go to surgery and then get adjuvant osimertinib, and then maybe the N2 patients will get an osimertinib-containing regimen as an induction therapy. I think one of the questions is does it really matter when you get the osimertinib as long as you get it at some point? And I think that's going to be the critical interpretation of some of the data at this point. Dr. Ece Cali: And how do you think this trial shapes the future research for patients with resectable EGFR-mutated lung cancer? Dr. Thomas Stinchcombe: Well, I mean, I think it shows that chemotherapy was really modestly active with an MPR rate of 2%, no pathological responses. And then I think you're going to have to look at an osimertinib plus another targeted therapy component. I think, you know, when I looked at the osimertinib versus the chemo-osimertinib arm, I also was sort of surprised that the MPR rate and the path CR rate were very, very similar. So I think that the question is would a double targeted therapy approach or some other approach matter? And I think it also sets a safety standard. And you touched on this in your comments, that there was not a disparity in terms of the rate of going to surgery or R0/R1 resections. So patients were not having progressive disease events or toxicities that prevented surgery. So I think it does give us good safety data. Dr. Ece Cali: Tom, thank you so much for sharing your insights on the JCO article, "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting, and please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

fWotD Episode 2947: Radar, Gun Laying, Mk. I and Mk. II Welcome to Featured Wiki of the Day, your daily dose of knowledge from Wikipedia's finest articles.The featured article for Friday, 30 May 2025, is Radar, Gun Laying, Mk. I and Mk. II.Radar, Gun Laying, Mark I, or GL Mk. I for short, was a pre-World War II radar system developed by the British Army to provide range information to associated anti-aircraft artillery. There were two upgrades to the same basic system, GL/EF (Elevation Finder) and GL Mk. II, both of which added the ability to accurately determine bearing and elevation. The name refers to the radar's ability to direct the guns onto a target, known as gun laying.The first GL set was an elementary design developed from 1936 onward. Based on the early Chain Home radar's electronics, GL used separate transmitters and receivers located in wooden cabins mounted on gun carriages, each with its own antennas that had to be rotated to point at the target. The transmitted signal was quite wide, in a fan shape about 120 degrees across. This made it useful only for measuring slant range information; target bearing accuracy was approximately 20 degrees, and it could not provide any elevation information. Several were deployed with the British Expeditionary Force and at least one was captured by German forces during the Dunkirk evacuation. The subsequent German evaluation led them to believe that British radar was much less advanced than German radar.Plans to address these shortcomings were underway even as the first Mk. I units were reaching service in 1939, but these Mk. II units would not be available until 1940 at the earliest. An expedient solution was the GL/EF attachment, which provided bearing and elevation measurements accurate to about a degree. With these improvements, the number of rounds needed to destroy an aircraft fell to 4,100, a tenfold improvement over early-war results. About 410 of the Mk. I and slightly modified Mk. I* units had been produced when production moved to the Mk. II, which had enough accuracy to directly guide the guns. Higher accuracy and simpler operation lowered the rounds-per-kill to 2,750 with Mk. II. After the German invasion of the Soviet Union in 1941, about 200 Mk. II units were supplied to the Soviets who used them under the name SON-2. By the end of the production run, 1,679 Mk. IIs had been produced.The introduction of the cavity magnetron in 1940 led to a new design effort using highly directional parabolic antennas to allow accurate ranging and bearing measurements from much smaller antennas. These GL Mk. III radar units were produced in the UK as the Mk. IIIB and a locally designed model from Canada as the Mk. IIIC. Mk. II remained in service in secondary roles as Mk. III's replaced them at the front. Both of these were replaced by the superior SCR-584 starting in 1944.This recording reflects the Wikipedia text as of 00:30 UTC on Friday, 30 May 2025.For the full current version of the article, see Radar, Gun Laying, Mk. I and Mk. II on Wikipedia.This podcast uses content from Wikipedia under the Creative Commons Attribution-ShareAlike License.Visit our archives at wikioftheday.com and subscribe to stay updated on new episodes.Follow us on Mastodon at @wikioftheday@masto.ai.Also check out Curmudgeon's Corner, a current events podcast.Until next time, I'm neural Arthur.

hour one: "blue trane" (live excerpt from kulttuuritalo helsinki, finland nov. 22, 1961) john coltrane w/eric dolphy "love is a wish away" faith nyc "I stood up" faith nyc "ripped headline" midwestern medicine "independent animal" guided by voices "before I cry" matt nelson "sustain and ring 2" roscoe mitchell quartet "flight" aerocobra "red-handed" bomis prendin title unknown (live excerpt from 'tubby's' in kingston, ny on feb 1, 2025) sky furrows "macrodoser" the illness "eagle street" faith nyc hour two: "can I make it up to you?" faith nyc "frank sinatra drive" alan licht "the light on - sound meditation 1" (excerpt) david first "love in a silent way" faith nyc "useless" faith nyc "half smoked cigarette" dead bandit "aniara" (act I canto IIIb) relay station + david dellacroce + hatsune miku & friends + oona pearsons symfauxnic partchchestra "juxtaposition" barry stock "everything is always around you" faith nyc hour three: "overpass" faith nyc "cymbal" martina berther "maris stella - plectere II" stefano pilia "back to the light" peaks "los dientes" muskeg mudsuck "hey joe" (prac prolly at quinn's house, late 1984) treacherous jaywalkers "climbing all the way to zion" faith nyc "soul secrets" (live at 'berlin under a' in manhattan, ny on nov 18, 2022) faith nyc "1_2_toques 03" hubbard-liebig "lemonade love stand" (live at 'c'mon everybody' in brooklyn, ny on oct 4, 2018) faith nyc

Este episodio es un #repost, porque llega el verano y sacaré episodios nuevos después de una pausa para descansar y coger fuerzas. Pero en estas semanas publicaré de nuevo una selección de relatos que representan las muchas formas que hay de parir y de transitar esta experiencia tan intensa. Todas las historias son importantes, y no es fácil elegir unos poquitos. Espero que escuchar estos relatos (por primera o siguiente vez) te acerque al mensaje que estás buscando aquí. Aprovecho para darte las gracias (un millón de veces gracias!) por estar aquí, haber encontrado este programa, escucharlo, compartirlo, apoyarlo. Significa para mí más de lo que puedo expresar con palabras. Estoy profundamente agradecida a cada mujer (y algún hombre!) que ha compartido su historia en Planeta Parto - a ti por escuchar el programa - y los mensajes que recibo por DM o email. Me conmueve profundamente saber que este programa te ayuda a transformar miedo en ganas, dudas en claridad, inseguridad en poder, recuerdo traumático en paz. No dejes de escribirme, te leo y (creo que) contesto todos los mensajes, aunque tarde un poquito. Mi contacto más directo está en Instagram https://instagram.com/planetaparto.podcast/ o por email en isa@planetaparto.es Esta semana te presento (de nuevo) el episodio que grabé con Lucía Gutierrez en verano de 2021. Vas a flipar con el relato de hoy, porque después de un primer parto inducido, con un dolor insoportable, epidural, uso de forceps y una episiotomía brutal que la tuvo casi un mes sin poder sentarse, Lucía quería tener un segundo parto con el menor número de intervenciones posible. Lo que Lucía no se podía esperar es que su parto fue tan rápido que no llegó a tiempo al hospital y dio a luz en el coche, en la autopista, asistida por su marido y con una tranquilidad y entereza impresionantes. El parto de Lucía fue rápido, seguro y fácil. En palabras de Lucía: "Ha sido una experiencia brutal. Venía de un primer parto muy medicalizado y con un desgarro IIIB y éste ha sido un regalo y además con 0 desgarros. Que nadie te diga que no sabemos parir. Sabemos perfectamente." Espero que disfrutes este episodio. Clica PLAY y empezamos!

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.

Original by Leopold Aschenbrenner, this summary is not commissioned or endorsed by him. Short Summary Extrapolating existing trends in compute, spending, algorithmic progress, and energy needs implies AGI (remote jobs being completely automatable) by ~2027. AGI will greatly accelerate AI research itself, leading to vastly superhuman intelligences being created ~1 year after AGI. Superintelligence will confer a decisive strategic advantage militarily by massively accelerating all spheres of science and technology. Electricity use will be a bigger bottleneck on scaling datacentres than investment, but is still doable domestically in the US by using natural gas. AI safety efforts in the US will be mostly irrelevant if other actors steal the model weights of an AGI. US AGI research must employ vastly better cybersecurity, to protect both model weights and algorithmic secrets. Aligning superhuman AI systems is a difficult technical challenge, but probably doable, and we must devote lots of [...] ---Outline:(00:13) Short Summary(02:16) 1. From GPT-4 to AGI: Counting the OOMs(02:24) Past AI progress(05:38) Training data limitations(06:42) Trend extrapolations(07:58) The modal year of AGI is soon(09:30) 2. From AGI to Superintelligence: the Intelligence Explosion(09:37) The basic intelligence explosion case(10:47) Objections and responses(14:07) The power of superintelligence(16:29) III The Challenges(16:32) IIIa. Racing to the Trillion-Dollar Cluster(21:12) IIIb. Lock Down the Labs: Security for AGI(21:20) The power of espionage(22:24) Securing model weights(24:01) Protecting algorithmic insights(24:56) Necessary steps for improved security(26:50) IIIc. Superalignment(29:41) IIId. The Free World Must Prevail(32:41) 4. The Project(35:12) 5. Parting Thoughts(36:17) Responses to Situational AwarenessThe original text contained 1 footnote which was omitted from this narration. --- First published: June 8th, 2024 Source: https://forum.effectivealtruism.org/posts/zmRTWsYZ4ifQKrX26/summary-of-situational-awareness-the-decade-ahead --- Narrated by TYPE III AUDIO. ---Images from the article:Apple Podcasts and Spotify do not show images in the episode description. Try Pocket Casts, or another podcast app.

Original by Leopold Aschenbrenner, this summary is not commissioned or endorsed by him. Short Summary Extrapolating existing trends in compute, spending, algorithmic progress, and energy needs implies AGI (remote jobs being completely automatable) by ~2027. AGI will greatly accelerate AI research itself, leading to vastly superhuman intelligences being created ~1 year after AGI. Superintelligence will confer a decisive strategic advantage militarily by massively accelerating all spheres of science and technology. Electricity use will be a bigger bottleneck on scaling datacentres than investment, but is still doable domestically in the US by using natural gas. AI safety efforts in the US will be mostly irrelevant if other actors steal the model weights of an AGI. US AGI research must employ vastly better cybersecurity, to protect both model weights and algorithmic secrets. Aligning superhuman AI systems is a difficult technical challenge, but probably doable, and we must devote lots of [...] ---Outline:(00:12) Short Summary(02:16) 1. From GPT-4 to AGI: Counting the OOMs(02:23) Past AI progress(05:37) Training data limitations(06:41) Trend extrapolations(07:57) The modal year of AGI is soon(09:29) 2. From AGI to Superintelligence: the Intelligence Explosion(09:36) The basic intelligence explosion case(10:46) Objections and responses(14:06) The power of superintelligence(16:28) III The Challenges(16:31) IIIa. Racing to the Trillion-Dollar Cluster(20:58) IIIb. Lock Down the Labs: Security for AGI(21:05) The power of espionage(22:09) Securing model weights(23:46) Protecting algorithmic insights(24:41) Necessary steps for improved security(26:35) IIIc. Superalignment(29:15) IIId. The Free World Must Prevail(32:15) 4. The Project(34:47) 5. Parting Thoughts(35:51) Responses to Situational AwarenessThe original text contained 1 footnote which was omitted from this narration. --- First published: June 8th, 2024 Source: https://forum.effectivealtruism.org/posts/zmRTWsYZ4ifQKrX26/summary-of-situational-awareness-the-decade-ahead --- Narrated by TYPE III AUDIO.

In this episode, Jonathan Appelbaum, MD, FACP, AAHIVS, discusses the newest data supporting LA ART use in people with adherence challenges or viremia, including:The LATITUDE study, an open-label phase III study of LA CAB + RPV in people with a suboptimal response or nonadherence to oral ARTUpdates to the Ward 86 cohort, which showed 81% of patients with viral suppression on LA CAB + RPV at Week 48The CARES study, an open-label, noninferiority phase IIIb study of LA CAB + RPV in people with baseline resistance mutationsPresenter:Jonathan Appelbaum, MD, FACP, AAHIVSLaurie L. Dozier, Jr., MD Education Director and Professor of Internal MedicineChair, Department of Clinical SciencesFlorida State University College of MedicineMedical DirectorCare Point Health and WellnessTallahassee, FloridaLink to the full program:https://bit.ly/49x0W6DLink to the slideset: https://bit.ly/4bzZothTo get access to all of our new podcast episodes, subscribe to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts or Spotify.  

As Colorectal Cancer Awareness Month 2024 comes to a close, Further Together host Michael Holtz, a 12-year survivor of stage IIIB colorectal cancer, talks to Eric Mayer and Jessica Etheridge, CEO and director of marketing and branding, respectively, for Knoxville-based New Day Diagnostics. This March, New Day launched ColoHealth, a screening blood test for people at average risk of developing colorectal cancer. They talk about the importance of prevention and early detection, the rise in colorectal cancer rates among people under age 50, and the changing scientific landscape for early detection tests. Learn more at https://newdaydiagnostics.com/

Acabou o carnaval! Los Hermanos tinham razão. No 1º programa oficial de 2024 Igor Giroto e Luiz Alcamim separam mais discos das suas coleções para debater. Do black metal ao hardcore caótico, a resenha promete. Senta na cadeira e vem com nóis! † COMPRE NOSSO MERCH: ⁠⁠⁠⁠⁠⁠⁠⁠https://bailedocapiroto.com.br⁠⁠⁠⁠⁠⁠⁠⁠ † INSCREVA-SE EM NOSSO CANAL: ⁠⁠⁠⁠⁠⁠⁠⁠https://www.youtube.com/bailedocapiroto⁠⁠⁠⁠⁠⁠⁠⁠ † SIGA-NOS NO INSTAGRAM: ⁠⁠⁠⁠⁠⁠⁠⁠https://instagram.com/bailedocapiroto⁠⁠⁠⁠⁠⁠⁠⁠ † SIGA-NOS NO TWITTER: ⁠⁠⁠⁠⁠⁠⁠⁠https://twitter.com/BaileCapiroto⁠⁠⁠⁠⁠⁠⁠⁠ † NOSSA CHAVE PIX CASO QUEIRA NOS APOIAR: bailedocapiroto@gmail.com --- Send in a voice message: https://podcasters.spotify.com/pod/show/bailedocapiroto/message

Trevor Maxwell was diagnosed with Stage IV colorectal cancer in March 2018. During his treatment journey he was dismayed to learn that support services specifically geared to men are sorely lacking, so he set out to change that. In 2019, he launched Man Up to Cancer, an organization that encourages men facing all forms of cancer to avoid isolation and connect with each other. Men find connection in The Howling Place, a private Facebook group, in 40-plus chapters across North America and around the world, and at an annual retreat called the Gathering of Wolves. MUTC also offers chemo backpacks to men undergoing chemotherapy, and is piloting men-only support groups at five cancer centers in 2024. The organization achieved non-profit status in November 2023 to continue its efforts to reach even more men who are not on social media, and to continue to provide all services at no cost. Further Together host Michael Holtz, a 12-year survivor of stage IIIB rectal cancer, is a member of the MUTC board of directors and recently recommended an ORAU-Directed Research and Development project to study the importance of peer-to-peer support for men facing cancer as part of his white paper, "Meeting the Moment: Aligning ORAU capabilities with the federal government's priorities to end cancer as we know it." Holtz and Maxwell discuss all things MUTC, the importance of peer-to-peer connection for men's mental and physical health, and how research will play a key role in reaching even more men in the future. To learn more about Man Up to Cancer, visit manuptocancer.org.

This message specifically deals with our stewardship of God's words, and the opportunities God gives us to invest them in the souls of men. May God move all of us to be faithful stewards of the time, talent and treasure he has entrusted to us.

20 gennaio 2024 III B Ordinario

All eyes are on Ayodhya today. The Ram Temple is all decked up, waiting for the consecration ceremony by a battery of priests led by an elderly Kashi Acharya. Prime Minister Narendra Modi is the ‘Jajman' or chief guest at the event -- which will be witnessed by millions. And many of them will soon embark on a journey to seek blessings from the deity. The tiny temple city will soon turn into a mega pilgrimage spot. But what does it mean for the future of religious tourism?  After the temple inauguration, the next big event that will be keenly watched is the tabling of the interim budget. General elections are near, and there are expectations that the government may loosen its purse strings for welfare schemes. Even as Finance Minister Nirmala Sitharaman has ruled out any such “spectacular announcements”. In the third edition of our special series on interim budget, Bhaswar Kumar speaks to experts to find out if welfarism will indeed get a further boost? And if yes, will it impact fiscal discipline?  Financial market too is eagerly waiting for the interim budget. It has its wish list ready. But right now, it looks like all the roads are leading to Ayodhya. Hopes of a tourism-led economic boom have also seen stocks of travel and hospitality companies shoot up in recent weeks. So, should you join this rally or wait as valuations may test the optimism?  An IMD forecast says that Ayodhya is likely to be sunny today, during the inauguration of the temple. But rest of the north India is still reeling under fog and cold wave. Hundreds of flights have either been cancelled, or are being delayed at the Delhi airport -- which will soon open its second CAT III- B runway. But what is this landing system? How does it help aircraft land during foggy conditions? Listen to this episode of the podcast for answers.  

In this episode, Brian Slomovitz, MD, MS, FACOG, and Keiichi Fujiwara, MD, PhD, share their thoughts and opinions on seminal data presented at the 2023 IGCS annual meeting for endometrial, ovarian, and cervical cancers, including:Phase III NRG GY018 trial of carboplatin and paclitaxel with or without pembrolizumab followed by pembrolizumab or placebo maintenance for 2 years in patients with measurable stage III/IVA, stage IVB, or recurrent endometrial cancer. Phase III ENGOT-EN6/GOG-3031/RUBY trial of carboplatin and paclitaxel with or without dostarlimab followed by dostarlimab or placebo maintenance for 3 years in patients with primary advanced or recurrent endometrial cancer. Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancer.Randomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of carboplatin and paclitaxel vs durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancer.An international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE).Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy vs placebo plus chemoradiation in patients with high-risk locally advanced cervical cancer.Phase III ICON8B study comparing carboplatin, paclitaxel, and bevacizumab every 3 weeks vs dose-dense weekly paclitaxel plus bevacizumab every 3 weeks in newly diagnosed high-risk epithelial ovarian cancer, either stage III (with residual disease or requiring new adjuvant chemotherapy) or stage IV.Presenters:Brian Slomovitz, MD, MS, FACOGDirectorGynecologic OncologyMount Sinai Medical CenterProfessorObsterics and GynecologyFlorida International UniversityMember, Board of DirectorsGOG FoundationUterine Cancer LeadGOG PartnersMiami, Florida Keiichi Fujiwara, MD, PhDProfessor of Gynecologic OncologySaitama Medical University International Medical CenterHidaka, JapanProfessor of OBGYNInternational University of Health and WelfareNarita, JapanThis educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/424E3Uq

Join our hosts Can Gollmann-Tepeköylü and Miia L Lehtinen for their late-breaking trials highlights presented at the 37th EACTS Annual Meeting in Vienna, including:  (2:40 - 8:53) Subannular Repair for Secondary Mitral Regurgitation with restricted systolic leaflet Motion (type IIIb): 2-year results from REFORM-MR registry by Dr Jonas Pausch   (8.53 - 13:47) Mechanistic insights from the CAST-HF trial: Transcriptomic analysis of human myocardial biopsies reveal biglycan as crucial mediator of angiogenesis by Dr Johannes Holfeld   (13.47 - 20:55) First-in-human experience with a novel custom-made double branch stent graft for aortic arch repair – The NEXUS DUO by Prof Mario Louis Lachat & Dr P Buyl   (20:56 - 25:28) Real World Experience of 510 On-X Aortic Valve Replacement Patients Treated with Low Dose Warfarin by Prof Aungye OO   (25:28 - 32:1) CEASE-AF: Effectiveness and safety of hybrid epicardial and endocardial ablation in patients with persistent and longstanding persistent atrial fibrillation by Dr Piotr Suwalski.

In this episode, Isabelle Ray-Coquard, MD, PhD, and Ana Oaknin, MD, PhD, provide expert insights on new clinical trial data presented at the 2023 ESMO annual congress for endometrial, ovarian, and cervical cancers, including:Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancerRandomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancerFirst results from a phase II biomarker-directed platform study with assigned treatments for patients with measurable persistent or recurrent platinum-resistant epithelial ovarian cancer based on tumor-specific molecular alterations (ENGOT-GYN/GOG-3051/BOUQUET)Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy in patients with high-risk locally advanced cervical cancerAn international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE)Primary results from the global, randomized phase III BEATcc trial of atezolizumab plus platinum-based chemotherapy + bevacizumab as frontline treatment in patients with persistent, recurrent, or metastatic cervical cancerInterim analysis results from the global, randomized, open-label phase III innovaTV 301 study of tisotumab vedotin vs investigator's choice of chemotherapy in second-line or third-line recurrent/metastatic cervical cancerPresenters:Ana Oaknin, MD, PhDHead of Gynaecologic Cancer ProgrammeDepartment of Medical OncologyVall d' Hebron University HospitalVall d'Hebron Institute of OncologyBarcelona, SpainIsabelle Ray-Coquard, MD, PhDPresident of the Gineco GroupCentre Leon BérardLaboratories RESHAPE Université Claude Bernard Lyon EstLyon, FranceThis educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/424E3Uq

La Dra. Flavia Morales, en conjunto con la Dra. Claudia Cano, ambas oncólogas médicas adscritas al Instituto Nacional de Cancerología en la ciudad de México, México, nos hablan sobre los estudios más relevantes en tumores ginecológicos presentados durante ESMO 2023: Cáncer de cérvix INTERLACE: estudio clínico aleatorizado, fase III, en pacientes con carcinoma escamoso, adenocarcinoma o adenocarcinoma escamoso en estadio IB1 positivo para ganglios, IB2, II, IIIB, IVA que recibieron al azar (1:1) quimioterapia más radioterapia (5 ciclos de cisplatino semanal) o quimioterapia de inducción (6 semanas de carboplatino/paclitaxel), seguida de la misma quimioterapia más radioterapia en la semana 7. Se informa que se recomendó una dosis total mínima mandatoria de EQD2 de 78Gy en el Punto A con braquiterapia 3D. KEYNOTE-A18: estudio fase III y doble ciego, que evaluó la eficacia y seguridad de pembrolizumab en combinación con quimioterapia más radioterapia concurrente en pacientes con cáncer cervical localmente avanzado, recién diagnosticadas y no tratadas previamente. Las pacientes fueron asignadas aleatoriamente (1:1) para recibir 5 ciclos de pembrolizumab (200 mg) o placebo cada 3 semanas en combinación con quimioterapia más radioterapia concurrente, seguidos de 15 ciclos de pembrolizumab (400 mg) o placebo cada 6 semanas. InnovaTV 301/ENGOT-cx12/GOG-3057: estudio global, aleatorizado (1:1), abierto, fase III, sobre tisotumab vedotin frente a la quimioterapia a elección del investigador (topotecán, vinorelbina, gemcitabina, irinotecán o pemetrexed) en segunda o tercera línea en pacientes con cáncer cervical recurrente o metastásico, que progresaron durante o después del tratamiento estándar con el doblete de quimioterapia ± bevacizumab ± terapia anti-PD-(L)1. Cáncer de ovario FLAMES: estudio fase III, aleatorizado (2:1), doble ciego y controlado con placebo, el cual tuvo como objetivo investigar la eficacia y seguridad de senaparib en pacientes chinas recién diagnosticadas con cáncer de ovario avanzado como terapia de mantenimiento en primera línea. Las pacientes elegibles tenían que haber completado la quimioterapia de primera línea a base de platino con respuesta completa o respuesta parcial. Cáncer de endometrio RUBY: análisis de la supervivencia libre de progresión y supervivencia global según la clasificación molecular del estudio aleatorizado (1:1) de dostarlimab o placebo, junto con carboplatino/paclitaxel, seguido de dostarlimab en monoterapia o placebo hasta por 3 años, para el tratamiento del cáncer de endometrio primario avanzado o recurrente. AtTEnd: estudio fase III, doble ciego y aleatorizado (2:1), que evalúa en pacientes con cáncer de endometrio con enfermedad avanzada o recurrente sin quimioterapia sistémica previa para la recurrencia, el uso de atezolizumab en combinación con carboplatino/paclitaxel o placebo, seguido de atezolizumab o placebo hasta la progresión de la enfermedad. DUO-E: resultados del estudio fase III de durvalumab más carboplatino/paclitaxel seguido de mantenimiento con durvalumab ± olaparib como tratamiento de primera línea para el cáncer de endometrio avanzado o recurrente recién diagnosticado. Fecha de grabación: 7 de noviembre de 2023.                 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.

Doctors Sara and Lisa talk to a GP involved in Primary Care Research Dr Imran Ghafoor and Ewa Grzegorska, a Research Support Facilitator from the National Health and Clinical Research Institute about Research in Primary Care. We talk through Dr Ghafoor's journey into being part of Primary Care Research, what embarking on Research Projects in Primary Care might look like, from the straightforward to the more involved, and some of the practicalities and financial considerations.  You can use these podcasts as part of your CPD - we don't do certificates but they still count :) Useful resources:  If you want to contact the research Team from today Directly: Researchsupport.CRNGM@NIHR.ac.uk or  I.gafoor1@NHS.net National Institute of Health and Care Research: https://www.nihr.ac.uk/ Clinicians wanting to Train up in Research Initial Training Module Good Clinical Practice (through National Institute for Health and Care Research): https://www.nihr.ac.uk/health-and-care-professionals/learning-and-support/good-clinical-practice.htm Implementation of inclisiran in UK primary care for patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents: rationale and design of VICTORION-Spirit, a pragmatic phase IIIb, randomised controlled study: https://www.ijclinicaltrials.com/index.php/ijct/article/view/672 Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial (mentioned and not published yet): https://pubmed.ncbi.nlm.nih.gov/37277072/ National Institute of Health and Care Research List of Possible Studies of Interest: https://bepartofresearch.nihr.ac.uk/results/search-results Some Primary Care professionals may also want to be a participant in research (which in itself is a nice way to see what it's all about). The best way to do this is to go to https://www.researchforthefuture.org/  ___ We really want to make these episodes relevant and helpful: if you have any questions or want any particular areas covered then contact us on Twitter @PCKBpodcast, or leave a comment on our quick anonymous survey here: https://pckb.org/feedback Email us at: primarycarepodcasts@gmail.com ___ This podcast has been made with the support of GP Excellence and Wigan CCG. Given that it is recorded with Greater Manchester clinicians, the information discussed may not be applicable elsewhere and it is important to consult local guidelines before making any treatment decisions.  The information presented is the personal opinion of the healthcare professional interviewed and might not be representative to all clinicians. It is based on their interpretation of current best practice and guidelines when the episode was recorded. Guidelines can change; To the best of our knowledge the information in this episode is up to date as of it's release but it is the listeners responsibility to review the information and make sure it is still up to date when they listen. Dr Lisa Adams, Dr Sara MacDermott and their interviewees are not liable for any advice, investigations, course of treatment, diagnosis or any other information, services or products listeners might pursue as a result of listening to this podcast - it is the clinicians responsibility to appraise the information given and review local and national guidelines before making treatment decisions. Reliance on information provided in this podcast is solely at the listeners risk. The podcast is designed to be used by trained healthcare professionals for education only. We do not recommend these for patients or the general public and they are not to be used as a method of diagnosis, opinion, treatment or medical advice for the general public. Do not delay seeking medical advice based on the information contained in this podcast. If you have questions regarding your health or feel you may have a medical condition then promptly seek the opinion of a trained healthcare professional.

La Dra. Florencia Cuadros, oncóloga clínica del Hospital Eva Perón, y el Dr. Matías Chacón, oncólogo médico adscrito al Instituto Alexander Fleming ambos de Argentina, nos hablan sobre los estudios más relevantes en melanoma presentados durante ESMO 2023: Estadios tempranos SWOG 1801: estudio aleatorizado, fase II de pembrolizumab adyuvante vs. pembrolizumab neoadyuvante en pacientes con melanoma en estadio IIIB clínicamente detectable y estadio IVC que era susceptible de resección quirúrgica. El objetivo primario fue la supervivencia libre de eventos (SLE) en la población por intención de tratar. KEYNOTE-942: estudio abierto, aleatorizado, fase II, evaluó si la terapia adyuvante posoperatoria con mRNA-4157 y pembrolizumab mejoró la supervivencia libre de recurrencia (SLR) en comparación con pembrolizumab solo en pacientes con resección completa del melanoma cutáneo y un alto riesgo de recurrencia en estadio IIIB/C/D y IV. Estadios avanzados SECOMBIT: estudio fase II,  no comparativo, aleatorizado, de tres brazos, para pacientes con melanoma metastásico con mutación BRAF V600 no tratado, que fueron asignados aleatoriamente al grupo A (encorafenib + binimetinib hasta progresión de la enfermedad, seguido de ipilimumab + nivolumab), grupo B (ipilimumab + nivolumab hasta la progresión de la enfermedad, seguido de encorafenib + binimetinib), o grupo C (encorafenib + binimetinib seguido de ipilimumab + nivolumab hasta la progresión de la enfermedad seguida de encorafenib + binimetinib). CheckMate 204: estudio fase II, multicéntrico, abierto, incluyó a pacientes adultos (edad ≥18 años) con melanoma de metástasis cerebrales medible (0.5–3.0 cm de diámetro). Los pacientes asintomáticos (cohorte A) tenían un ECOG de 0 o 1 y no tenían síntomas neurológicos, ni uso inicial de corticosteroides; los pacientes sintomáticos (cohorte B) tenían un estado funcional ECOG de 0 a 2, con síntomas neurológicos estables y podrían estar recibiendo dosis bajas de dexametasona. NIBIT M2: estudio fase III, reclutó a pacientes >18 años con melanoma BRAF mutado y metástasis cerebrales activas, asintomáticas y no tratadas, aleatorizados (1:1:1) a fotemustina o ipilimumab + fotemustina o ipilimumab + nivolumab. TACo-BEAT-MBM: estudio fase II, que evaluó qué tan bien funcionaba bevacizumab y atezolizumab con o sin cobimetinib en el tratamiento en pacientes con melanoma no tratado que se ha diseminado al cerebro. NCT03025256: estudio fase I/Ib, para pacientes >18 años con melanoma metastásico y evidencia de enfermedad leptomeníngea por resonancia magnética y/o citología del LCR, ECOG PS ≤2 , que fueron tratados de forma simultánea con nivolumab intratecal e intravenoso. Se permitió el tratamiento concurrente con inhibidor de BRAF/MEK y dexametasona ≤4 mg/día. IMCgp100-202: estudio abierto, fase III, aleatorizados al azar, en pacientes con melanoma uveal metastásico positivo para HLA-A*02:01 no tratados previamente en una proporción de 2:1 para recibir tebentafusp o la terapia elegida por el investigador con un solo medicamento, pembrolizumab, ipilimumab o dacarbazina, estratificados según el nivel de lactato deshidrogenasa.

HBCU Gameday takes our third look into the story of the Florida Blue Florida Classic. This stop is in Daytona Beach as we take a look at "The Pride." The B-CU Marching Wildcats and band director Dr. Donovan Wells talk about preparations for the classic battle. #ncaa #ncaabands #hbcu #hbcubands #bcu #bcuband #floridaclassic #floridablue #hbcugameday

Bienvenidos a este podcast donde se abordarán los temas de mayor interés en el ámbito oncológico para Latinoamérica. A lo largo de este proyecto los Dres. Diego Ballén y Mauricio Lema, oncólogos clínicos colombianos, entrevistarán a un invitado especial para abordar con base en evidencia científica y a su experiencia a aquellas interrogantes que llegan a surgir diariamente en la práctica clínica. Durante este episodio el Dr. Andrés Felipe Cardona, oncólogo clínico, Director de Investigación y Educación Científica de la Fundación CTIC en Bogotá, Colombia, discutirá en conjunto con nuestros coordinadores sobre la inmunoterapia neoadyuvante en cáncer de pulmón. Los datos que se abordaron están basados en 5 estudios que inscribieron a pacientes con cáncer de pulmón de células no pequeñas. El primero que se comentó fue el CheckMate 816, un estudio fase III, aleatorizado, de nivolumab + quimioterapia doble con platino frente a la quimioterapia en pacientes con enfermedad temprana que no presentaban mutaciones de EGFR y ALK. El segundo estudio fue el NADIM II, un fase II, que examinó la respuesta patológica completa con nivolumab + quimioterapia (paclitaxel y carboplatino) neoadyuvante o solo quimioterapia en pacientes con enfermedad localmente avanzada y resecable, sin mutaciones de EGFR y ALK; si los pacientes alcanzaban resección completa se les brindaba nivolumab por 6 meses. El siguiente estudio que se discutió fue el AEGEAN, un estudio fase III, aleatorizado, de durvalumab neo/adyuvante + quimioterapia basada en platinos en comparación con la quimioterapia para el tratamiento de pacientes con enfermedad resecable en estadios II y III. El cuarto estudio que explicaron fue el KEYNOTE-671, un fase III, aleatorizado, de quimioterapia doble con platino +/- pembrolizumab como terapia neo/adyuvante para pacientes con enfermedad resecable en estadio II, IIIA y IIIB. El último estudio que se trató fue el NEOTORCH, un fase III, aleatorizado, de toripalimab + quimioterapia doble con platino en comparación con quimioterapia para pacientes en etapas II – III, resecable. Con base en los resultados presentados de cada estudio, los expertos respondieron a las siguientes interrogantes: ¿Actualmente la quimioterapia + inmunoterapia neoadyuvante es un estándar de tratamiento en cáncer de pulmón? ¿Qué implica que un paciente alcance respuesta patológica completa o mayor? ¿Sería importante recibir en el reporte de patología estos resultados de forma regular? ¿Qué opinión hay del grupo EGFR mutado que se agregó en el estudio KEYNOTE-671? En el caso de pacientes resecables, sin mutaciones de EGFR y ALK conocidas y con expresión alta de PD-L1 ¿sería apropiado un tratamiento neoadyuvante con quimioterapia + inmunoterapia o un tratamiento convencional seguido de inmunoterapia adyuvante? ¿Qué es el efecto de muerte inmunogénica de la quimioterapia? ¿qué diferencias existen entre los citotóxicos disponibles? ¿Cómo se valora el flare nodal inmunológico? ¿Vale la pena reestadificar el mediastino después del tratamiento neoadyuvante con quimioterapia + inmunoterapia? Considerando que no hubo una participación Latinoamericana sustancial en ninguno de estos estudios, excepto por el AEGEAN, ¿existe alguna razón para considerar que la respuesta a la quimiterapia + inmunoterapia neoadyuvante en población latina funcione diferente? Fecha de grabación: 4 de septiembre de 2023. El podcast “ACHO: actualidad del cáncer en Colombia” es una iniciativa de ACHO.        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.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research advances in treating non-small cell lung cancer, small cell lung cancer, and mesothelioma.  Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the 2023 Cancer.Net Associate Editor for Lung Cancer. Dr. Melina Marmarelis is an assistant professor at the University of Pennsylvania, the Medical Director of the Penn Medicine Mesothelioma Program, and the co-director of the Molecular Tumor Board at the University of Pennsylvania. She is also the 2023 Cancer.Net Specialty Editor for Mesothelioma. Dr. Kristin Higgins is a radiation oncologist, Professor and Vice Chair in Clinical Research in the Department of Radiation Oncology at Emory University School of Medicine and medical director of radiation oncology of The Emory Clinic at Winship Cancer Institute's Clifton campus location. She is also a 2023 Cancer.Net Advisory Panelist for Lung Cancer. You can view disclosures for Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net Research Round Up podcast. Today, we will be talking about the latest research from the Annual Meeting of the American Society of Clinical Oncology from June 2023, and I'm joined today by 2 experts in the field of lung cancer. Before I introduce them, I'd like to introduce myself. I'm Dr. Charu Aggarwal. I'm an associate professor for lung cancer excellence at the University of Pennsylvania's Abramson Cancer Center. I'd now like to introduce Dr. Melina Marmarelis. Dr. Marmarelis: Hi, so happy to be here. I'm Melina Marmarelis. I'm an assistant professor at the University of Pennsylvania and the medical director of the Penn mesothelioma program. Dr. Aggarwal: And Dr. Kristin Higgins. Dr. Higgins: Hi, everyone. I'm Kristin Higgins. I am a thoracic radiation oncologist at Winship Cancer Institute of Emory University. I'm a professor and vice chair for clinical research for radiation oncology. Dr. Aggarwal: Fantastic. So today, we'll talk about relevant research as it applies to practical implications in the clinic for practitioners, but most importantly, patients with lung cancer. I'd like to start off by discussing 2 key studies, and I would love for perspectives from our faculty here. The first study I want to highlight is the ADAURA trial. This is a trial that has already sort of changed practice in most recent years when the study was presented at the Annual Meeting of the American Society of Clinical Oncology in 2020, but we have new updates on this study as of 2023. So, in brief, this was a study that looked at the value of administering an oral pill called osimertinib that is a tyrosine kinase inhibitor against the EGFR, or the epidermal growth factor receptor, in patients with non-small cell lung cancer. We know that non-small cell lung cancer is quite a heterogeneous disease with some subsets of patients having mutations that may render them increasingly sensitive to the effects of these tyrosine kinase inhibitors. In fact, these pills have been used in the metastatic setting for several years based on an improvement in overall survival. What the ADAURA study tried to do was ask the question if this pill would add an incremental advantage after receiving curative-intent surgical resection in those with early-stage lung cancer. So this study enrolled patients with stage IB to IIIA non-small cell lung cancer after surgical resection and focused only on those patients that had sensitizing EGFR mutations with EGFR exon 19 deletion or L858R mutations. Patients could receive chemotherapy after having the surgery and then were basically randomized into 2 groups, one of whom received osimertinib at a dose of 80 milligrams once daily for a total of 3 years. Patients were followed up for recurrence. We already know from the earlier results that patients who received osimertinib had a better chance of delaying the recurrence of disease. However, what we found at the Annual Meeting this year is that the administration of this osimertinib also improved overall survival, which is really what we all look for in the oncology world. If you're administering a therapy, especially for a long duration, we want to be able to see a survival benefit, and that's what we saw. In fact, in patients who received osimertinib, there was a 49% less likelihood of dying from lung cancer compared to those who did not receive osimertinib. This, I think, is practice-affirming. It may not be practice-changing because some of the practitioners started using osimertinib after its FDA approval in December of 2020, but I think it just confirms our practice as it delivers an overall survival advantage in these patients. One thing that's increasingly important is to identify patients who have this mutation, so now we have efforts underway locally as well as nationally to perform molecular genotyping on all patients with lung cancer so that we can adequately and appropriately treat those with early-stage lung cancer following curative resection or following surgery. Melina and Kristin, what are your thoughts? Dr. Marmarelis: Well, I think these results are really important because it did, as you say, affirm kind of what we're already doing, but I think the most convincing part of this for me is the prevention of spread of disease to the brain. This is not comparing osimertinib after surgery versus osimertinib ever, which I think is a difficult part about interpreting this trial. But I think the fact that it prevented disease from going to the brain is really meaningful to everyone, to patients, to the physicians that are caring for them, so I think that's a really important endpoint. Dr. Higgins: I agree with Melina. I think this is really exciting for our patients. It's exciting to have more treatment options for early-stage lung cancer. I think patients that are diagnosed with early-stage lung cancer are highly motivated to do everything they can to improve their likelihood of being cured. So I tend to have a lot of conversations about side effects and toxicities with patients that have questions and are sort of wondering how it will affect their quality of life, and of course, that is an important piece of it because patients that do have curable lung cancer are probably starting off with a better overall quality of life, but I think generally speaking, our patients have tolerated it well. I'm also kind of excited from a radiation oncology point of view. We treat patients with stereotactic body radiation therapy [SBRT] that are medically inoperable. And we have another trial with a cohort looking at osimertinib for those patients that have EGFR mutations, too, and that's ongoing, again, applying the same concept of trying to really use these SBRTs that work really well in the advanced setting, moving them into earlier stages of disease to help us care for more patients. So overall, I think it's really exciting, and I think it's a huge win for the clinical research community. Dr. Aggarwal: Well, that's wonderful. And I think this certainly advances the field as this is the first targeted therapy approved for patients with early-stage non-small cell lung cancer. I should add that AstraZeneca, the company that makes this drug, has provided institutional research funding to my institution, and I also serve as an advisor to them, but I was not involved personally in the research of this clinical trial. I'd like to move on but stay within the field of early-stage lung cancer and talk about another study called the KEYNOTE-671 study, and this is important because it really applies the idea of using immunotherapy before and after surgical resection in patients with early-stage lung cancer. Just to give a little bit of background to our listeners, we now have 3 approvals for the use of immunotherapy in patients with early-stage lung cancer. Two of those are in the adjuvant setting, meaning that if a patient undergoes surgical resection or surgery for early-stage lung cancer, they can receive either atezolizumab or pembrolizumab following that surgery, and that has been shown to improve outcomes in terms of reducing the chances of recurrence. We also have another approval, which is the third approval in early-stage lung cancer, where 3 cycles of chemotherapy and immunotherapy are administered prior to surgery, also called as the neoadjuvant chemo-immunotherapy approach. This drug that has been approved in combination with chemotherapy is nivolumab, and this approval came from a clinical trial called CheckMate 816 that showed both that patients who received this neoadjuvant chemo-immunotherapy approach had a higher proportion of patients who had complete response or pathologic complete response in their tumors at the time of surgery and also showed that the chances of the disease coming back after surgical resection was much lower amongst those that had received this intervention. The current study, the KEYNOTE-671 study, builds upon this concept and adds both a before-surgery intervention as well as an after-surgery intervention. So what this study did was it enrolled patients with early-stage, stage II to IIIB non-small cell lung cancer, and patients in the intervention arm received 4 cycles of chemotherapy in combination with pembrolizumab, underwent surgery, and then received immunotherapy with pembrolizumab for up to 13 cycles. Patients in the control arm received only chemotherapy prior to surgery and then placebo for up to 13 cycles after. This was a large study with about 786 patients randomized, and what we found was that those patients that received the intervention had a much higher likelihood of remaining disease-free or event-free following surgical resection as well as in the early analysis, an improvement in overall survival with about a 27% reduction in the risk of death. So I do think that this is the first study that shows us that use of both neoadjuvant as well as adjuvant. So sort of this perioperative approach of using immunotherapy before and after surgical resection can actually lead to improved outcomes. This is ultimately what we want for our patients, improvement in overall survival, improvement in cure rates, etc. The study has been silent on the use of radiation therapy, although it has gone into details in terms of the kinds of surgery that was done. Kristin, what are your views about this? Dr. Higgins: I think postoperative radiation after resection for non-small cell lung cancer has sort of started to fall out of favor because of the Lung ART trial that was published in Europe, a randomized phase III trial that showed no differences in disease-free survival or overall survival. And that's not to say that there aren't more study questions on ways to give it safer and ways to incorporate radiation in with the chemo-IO approach, and there are some novel ways to do that, and we're going to see some data presented at the World Lung Cancer Conference looking at some of those novel approaches. But standardly, when patients receive neoadjuvant chemo-immunotherapy followed by surgery, we typically would not offer radiation. There are instances, though, when patients have positive margins, for example, and in that situation, it's sort of a discussion on a case-by-case basis. But ideally, we're hoping that most of these patients that go to surgery are able to get a complete resection, and that's really the key component of the decision-making for deciding if patients are eligible for this approach. Dr. Aggarwal: I agree. Melina, any additional thoughts on this trial? Dr. Marmarelis: I think it's an exciting trial for the reasons that you mentioned. I think it does bring up a number of questions about whether both neoadjuvant and adjuvant immunotherapy are needed. I tend to like the idea of having immunotherapy present when the tumor is present before surgery, so I like kind of having that on board, but I think we still don't know which is more important. Dr. Aggarwal: So it certainly raises many more questions, which hopefully will be answered in the future. KEYNOTE-671 trial was conducted by Merck that produces the drug Keytruda, or pembrolizumab. We have received institutional research funding for other trials. I was not personally involved in this clinical trial. I do serve as an advisor for Merck. I think we'll bring you more research from the ASCO Annual Meeting. And I'll turn it over to Dr. Marmarelis to discuss some more exciting research. Dr. Marmarelis: Thanks, Charu. So perhaps it's not surprising that one of the exciting things I picked from ASCO has to do with mesothelioma. And I just want to put into context a little bit about why this trial was important. This is IND227. It was a cooperative group trial done across Canada, France, and Italy, and this was chemotherapy plus or minus pembrolizumab in patients with pleural mesothelioma that did not undergo surgery. So this was their first treatment, and they were not undergoing surgery. And the reason this trial was important is that in the last few years, we had results from CheckMate 743, which was looking at IPI/NIVO, so a combination of immunotherapies versus chemotherapy. And there was an improvement in survival for those that received double immunotherapy, and that improvement was most pronounced in the non-epithelioid population, which is actually a smaller subset of pleural mesotheliomas. And so as we've seen in the lung when we look at immunotherapy versus chemo, it raises the question of whether combination immunotherapy plus chemotherapy would actually be better for all and, in particular, for all histologies in pleural mesothelioma. So this was looking at that concept. It took the standard chemotherapy, carboplatin-pemetrexed or cisplatin-pemetrexed, and then combined it with one immunotherapy, so slightly less than the combo immunotherapy seen in CheckMate 743, and that was pembrolizumab. And what they saw was that there was a small overall survival improvement in the group that got pembrolizumab. Again, that was most pronounced in patients in the non-epithelioid group, so those with sarcomatoid or biphasic histology. And this is really a prelude to several other trials that are coming out in mesothelioma, namely the DREAM3R trial, which is looking at chemotherapy plus or minus durvalumab. That control arm also includes IPI/NIVO, so that will be really important to be able to compare those, and then also the BEAT-meso trial, which is looking at chemotherapy-immunotherapy but also with an anti-VEGF agent, bevacizumab. So I think this was an important trial. It's a little bit of proof of concept, but there's still a lot that we're looking forward to. It's not quite practice-changing in the clinic, although I think it's certainly an option that people are using, but I'm looking for more data going forward. Dr. Aggarwal: It's incredible to see how far we've come in mesothelioma within the last decade. We are introducing immunotherapy. We're introducing novel agents in the first-line setting. Dr. Marmarelis: The other trial that I was interested in was KEYNOTE-789, which is looking also at patients with EGFR mutations and those that had the original osimertinib as their first-line treatment or another tyrosine kinase inhibitor and then had disease progression on that TKI. And this is an area of huge need. We have patients that do really well on targeted therapies, and then they have disease progression, and we're looking for additional targeted options, but we're also looking for effective chemotherapy options. And one of the questions that has risen from this is whether there's a role for immunotherapy. We know that immunotherapy alone in patients with EGFR mutations is not very effective when you look at a broad population, but in combination with chemotherapy, it's possible that it can add some benefit. So this trial looked at those that had EGFR mutations, had disease progression after a targeted therapy, and then it randomized them to chemotherapy plus or minus pembrolizumab, so chemotherapy plus or minus immunotherapy, and interestingly, it had no difference in the progression-free survival or the overall survival. So the 2 arms were really similar in terms of outcomes. There was also no difference in the overall response rates of the amount that the drug actually shrinks the tumor. So it really doesn't look like immunotherapy is adding much to chemotherapy for these patients. I think we still need to look a little bit closer because there are probably some patients with EGFR mutations that could benefit from immunotherapy, but we're really not very good at identifying those. One of the questions that comes up in this space is whether to add anti-VEGF treatment in addition to chemotherapy and immunotherapy. So there are some upcoming trials looking at that. Dr. Aggarwal: I think this was a trial that was actually very important and again, practice-affirming that this idea of continuing chemotherapy without adding immunotherapy, patients are not losing much. In fact, they're not gaining anything by adding immunotherapy as shown in this clinical trial. I think continuing immunotherapy, so continuing osimertinib, may be important in this setting also because we know that osimertinib can cross the blood-brain barrier. It can provide that CNS [central nervous system] protection. Dr. Marmarelis: Yeah, I think that's a great point that the comparison here is not chemotherapy plus osimertinib. It's chemotherapy alone. So I agree that the control arm is not quite what some of us do. I agree. I do the same as you do. I also just want to mention that the KEYNOTE trial and the previous trial about mesothelioma used pembrolizumab, which is made by Merck. We have received institutional funding, and I've served as an advisor as well as received honorarium from Merck.   Dr. Aggarwal: Melina, those were 2 very important studies and certainly, I think, answer some very relevant questions in clinic in the management of patients with EGFR-mutant lung cancer, for example. And then I think we look forward to more practice-changing data in mesothelioma. Kristin, I would love to hear research from ASCO from you. What caught your interest? Dr. Higgins: So I have a special interest in small cell lung cancer. And I think there was one important small cell lung cancer trial that I wanted to review with everyone. It was SWOG S1929. And SWOG is the Southwest Oncology Group, and it's a cooperative group that conducts clinical trials in cancer funded by the National Cancer Institute. And this is a randomized phase II trial of atezolizumab and chemotherapy followed by randomization to continuing the maintenance of atezolizumab with a PARP inhibitor. Now, we know from prior data that PARP inhibition is attractive for small cell lung cancer because PARP is expressed frequently in small cell lung cancer, and there is a biomarker called Schlafen-11 that preclinical data and prior data has shown can predict response to PARP inhibition. And this trial was sort of a proof-of-concept trial, a small, randomized phase II trial testing whether or not that Schlafen-11 biomarker could be used to direct therapy. Now, in this trial, there were 309 patients that were registered. They then had to have their tumor samples sent for central testing for the Schlafen-11 expression. One thing that I think is important to bring up is that in small cell lung cancer, there's this belief that it's really hard to get tissue samples from small cell lung cancer and it's a difficult thing logistically because it's just a lot harder to access these tumors. But interestingly, in this trial, 80% of patients had tumors that were evaluable for the biomarker, and the median time to the test result was only 7 days. So patients were able to get their tumor tested, get it sent out, get results in a rapid manner, and then be randomized based on these results. The primary endpoint for this trial was progression-free survival, and the primary endpoint was met. Progression-free survival was 4.2 months versus 2.8 months. Now, I think many people will say the magnitude of benefit here is not very much, but it's small cell lung cancer, and we don't have a lot of positive trials in this space, and we also don't have many trials that have used a biomarker to direct therapy. So I think for those reasons, it's really exciting to see these results. It was also conducted within a cooperative group with multiple different sites across the United States, and the fact of the matter is that we can do trials like this in small cell lung cancer patients, and I think it will sort of serve as a precedent for future trial design. Now, the overall survival for the trial is still premature. It didn't look that much different with the PARP inhibitor, but that doesn't mean that, again, things could change with more follow-up. And I really like the approach of this trial design, and I'm excited to see biomarker-driven trials in small cell lung cancer. Charu and Melina, what do you guys think about this study? And what do you think about our small cell lung cancer patients and our ability to conduct future trials like this? Dr. Aggarwal: I think this is certainly an advance. As you pointed out, Kristin, it shows us that we can conduct trials in the space. I think it offers a lens into the potential of personalized therapy in small cell lung cancer, which has eluded us for a very long time. The standard of small cell lung cancer has not changed significantly for a very long time, so I think this is very exciting and can't wait to see more things come in the future. Dr. Marmarelis: Yeah, I agree. I think we've always been asking for additional biomarkers, especially in such a difficult disease like small cell. And so this is really exciting to see potential biomarkers and that it was feasible to actually pose that question and study it. So that part's really exciting. Dr. Higgins: Great. And I should also say I was not involved in the study, and I'm not associated with any of the pharmaceutical companies that were involved in the study for S1929. And the final study that we wanted to talk about was the phase III LUNAR study, and this is sort of a different type of trial in the setting of advanced non-small cell lung cancer. It was studying tumor treatment fields with standard of care in metastatic non-small cell lung cancer after progression with platinum-based therapies. And first, I just want to step back and explain what tumor treating fields are. Tumor treating fields are applied to a patient with a transducer that's placed on the skin, and what it does is it applies an electrical field, and that disrupts mitosis when the cancer cells are trying to divide. And the mechanism of cell death is a little bit unclear. There are sort of many mechanisms that are postulated, one of which is immunogenic cell death, but we don't really know, I think, what's happening. But there have been studies that show improved results with tumor treating fields and other diseases. For example, particularly in glioblastoma multiforme, tumor treating fields are used in combination with surgery, radiation, and temozolomide (Temodar). So it's something that's being used in other disease sites, and this is some of the early data that we've seen in metastatic non-small cell lung cancer. And so in this trial, 276 patients were randomized to tumor treating fields plus standard of care or standard of care alone. Now, I should mention that this trial began enrolling patients in 2016, and so the standard of care was very different. After platinum-based therapies, the standard was considered docetaxel. Of course, platinum-based therapy alone for frontline treatment of advanced non-small cell lung cancer is also not the standard of care anymore. And so I think with that in the background, it does make interpretation of these results somewhat difficult, and that's probably the major caveat to this study. But nonetheless, patients were randomized, 276 patients. The primary endpoint of the study was overall survival. They were looking at progression-free survival and overall response rates as secondary endpoints as well as overall survival in patients that received immunotherapy versus just chemotherapy alone. And the trial was positive. Overall survival was improved. The median overall survival was 13.2 months for patients that received tumor treating fields with standard of care versus 9.9 months for standard of care alone. If you look at 3-year survival, it was 18% versus 7%. I think this is a new type of therapy for our patients with non-small cell lung cancer. It is somewhat of a difficult thing to wear the transducer, and you have to wear it for many, many hours. So that is one thing that I think can be difficult for patients that are using this treatment, but nonetheless, it is something new for advanced non-small cell lung cancer. I do know that the technology of tumor treating fields is being studied in other settings for non-small cell lung cancer, for stage III non-small cell lung cancer, for example, and also in the frontline setting. I think this trial kind of speaks to the fact that the landscape of advanced non-small cell lung cancer is changing so rapidly, and when we're studying something novel, we have to make sure that we make these trials feasible for enrollment so that we can get them completed rapidly, and we can get a readout and it doesn't become obsolete based on this shift in the standard of care. So I think it just really kind of drives home that we need to make sure that we're taking that into account with trial design. It's not standard of care changing right now, but it'll be interesting to see how the data evolves over time. Melina, I'm interested to hear your point of view because I know that these can be used in mesothelioma, maybe not that frequently. What is your experience with tumor treating fields, if any? Dr. Marmarelis: Tumor treating fields are approved as a device in pleural mesothelioma in the first-line setting in combination with chemotherapy. They have been used off-label in other settings, but that's the device approval. The trial that looked at tumor treating fields in mesothelioma was a single-arm trial, so there was no control arm, and it was really actually just looking at the safety of the device. So I have not used it personally in mesothelioma, although I know of patients and I know of real-world studies looking at its use, and I think it's potentially an interesting modality of treatment, especially in combination with immunotherapy, given that it really doesn't have a lot of additive toxicity. But I think the question is really, which patients are benefiting from it, and which patients are able to actually wear the vest in the case of mesothelioma? Dr. Higgins: Yeah. Any thoughts, Charu? Dr. Aggarwal: I agree, and I think this is going to be largely driven by patient experience. I think this is going to be quite onerous to wear this, carry the suitcase, so I would be very interested in patient reported outcomes as well as patient experiences and stories, which will really drive our use here. Dr. Higgins: Yeah, that's a great point. I should say that this trial was sponsored by Novocure. My institution does have other Novocure studies underway, and we receive research funding, but I was not involved in the study, and I did not personally receive any research funding. Dr. Aggarwal: Thank you, Kristin. This has been a wonderful review of practice-changing and some promising research that came out of the ASCO Annual Meeting. I hope our listeners enjoyed it, and we'll be sure to update you with the next annual research conference. Thank you, everyone. ASCO: Thank you, Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Dr. Michael Atkins and Dr. Vernon Sondak highlight the latest updates to the systemic therapy for melanoma recommendations in this newest guideline. The discussion covers neoadjuvant and adjuvant therapy for resected cutaneous melanoma, options for unresectable and/or metastatic cutaneous melanoma, and therapies for noncutaneous melanoma. They review the importance of this guideline and the most pressing outstanding questions to help inform better treatment strategies for patients with melanoma. Read the full guideline update, "Systemic Therapy for Melanoma: ASCO Guideline Update" at www.asco.org/melanoma-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/melanoma-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO. 23.01136 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Michael Atkins from Georgetown Lombardi Comprehensive Cancer Center, and Dr. Vernon Sondak from H. Lee Moffitt Cancer Center and Research Institute, authors on “Systemic Therapy for Melanoma: ASCO Guideline Update.”   Thank you for being here today, Dr. Atkins and Dr. Sondak. Dr. Vernon Sondak: Happy to be here. Dr. Michael Atkins: Yeah, it's a pleasure. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Sondak and Dr. Atkins, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content here, Dr. Sondak, what prompted this full update to the Systemic Therapy for Melanoma Guideline, which was initially published in 2018? Dr. Vernon Sondak: Well, the last 10 years or so have seen enormous advances in the management of metastatic melanoma and localized melanoma with systemic therapy, and the last few years haven't slowed up at all. So since 2018, we've seen new approvals, we've seen key pivotal trials that have shown some amazing results that we'll talk about, and all of these things together weighed into the decision to update the systemic therapy guidelines. Brittany Harvey: Great. Thank you for that background on what prompted the update. So then, this guideline provides updated recommendations across four clinical questions. I'd like to review the key updated recommendations for our listeners. So first, Dr. Sondak, what has changed in the updated recommendations regarding neoadjuvant therapy for adults with resectable cutaneous melanoma? Dr. Vernon Sondak: Neoadjuvant therapy is one of the most rapidly evolving and exciting parts of the management of melanoma with systemic therapy. The updated guidelines now include neoadjuvant pembrolizumab as a new recommendation for patients with resectable stage IIIB to IV cutaneous melanoma. This is based on the SWOG S1801 clinical trial, which was a very simple and yet incredibly influential clinical trial. It took patients with resectable metastatic melanoma, either metastatic to the lymph nodes or beyond, as long as it could be removed surgically, and randomized all of the patients to either get surgery, followed by a year of adjuvant pembrolizumab, which is very standard, or the same exact surgery and the same total amount of pembrolizumab, but with three of the doses given before surgery. So that simplicity, that ability to just compare the effect of neoadjuvant or preoperative pembrolizumab to entirely postoperative adjuvant pembrolizumab, made this trial a really pure assessment of the value of neoadjuvant pembrolizumab.  Impressively, this study showed a significant improvement in event-free survival for patients who got those three doses of pembrolizumab upfront. What's event-free survival? That includes relapse-free survival, but also the kinds of events that you can see happening with neoadjuvant therapy, such as progression of the disease prior to surgery that makes the patient unresectable. And the bottom line is that there was really the same number of issues with neoadjuvant pembrolizumab as with surgery, followed by adjuvant therapy, but there were many fewer recurrences among the patients who got neoadjuvant pembrolizumab. So that's why this was put into the guidelines. Brittany Harvey: Excellent. I appreciate you reviewing the evidence behind those recommendations and what's new for neoadjuvant therapy. So then, Dr. Atkins, moving into adjuvant therapy, for patients with resected cutaneous melanoma, what is new in the recommendations regarding adjuvant systemic therapy options? Dr. Michael Atkins: Sure. In the prior version, adjuvant therapy was recommended for patients with stage IIIB, IIIC, and for some patients with stage IV resected to NED. And those were based on studies with adjuvant pembrolizumab, adjuvant ipilimumab, and adjuvant nivolumab compared to ipilimumab. But what's happened since then is some really important adjuvant studies have been carried out in patients with stage IIB, IIC, and IIIA disease who are at slightly lower risk of recurrence, but still have substantial risk of recurrence, and make up a large percentage of the patients who eventually develop stage IV disease. And in these studies, one with pembrolizumab compared to placebo, there was about a 40% to 50% reduction in relapse-free survival observed, leading to the FDA approval of pembrolizumab in that setting. And then recently we saw the results of a similar study involving nivolumab that showed maybe even a slightly better reduction in the risk of relapse in that same patient population. Ultimately, this will lead to FDA approval as well. And we felt it was important to put in the guidelines the results of these studies so that people can have informed discussions with their patients about whether they want to receive this therapy going forward. It's important to point out that we don't have good data yet on overall survival. We just have data on relapse-free survival. So we don't, for sure, know that treating patients early, rather than waiting until a subset of them relapse and treating those late leads to an improved overall survival. That's an important discussion to have with patients to provide them with this option. In addition, we saw the results of the IMMUNED trial, which looked at nivo-ipi or nivo monotherapy versus placebo or observation in patients with stage IV disease that had been completely resected. And we saw dramatic improvement for the nivo-ipi combination compared to nivo or observation in those patients with stage IV NED. And we felt that, therefore, this was also an important patient population where we should offer guidance Brittany Harvey: Absolutely. That shared patient-clinician decision-making is paramount. And then you've both reviewed the options for resected cutaneous melanoma. But Dr. Atkins, what is new regarding systemic therapy options for patients with unresectable and/or metastatic cutaneous melanoma? Dr. Michael Atkins: Yes. For patients with unresectable metastatic cutaneous melanoma, there was a new drug combination that was approved combining nivolumab with relatlimab, which is an anti-lag-3 antibody that showed benefit compared to nivolumab monotherapy across almost all subgroups. In particular, the benefit was similar regardless of BRAF mutation status, regardless of elevated LDH, and regardless of patient stage. That led to FDA approval, and this is now an available treatment option, which is associated with less toxicity and similar efficacy to the standard of care nivo-ipi. In addition, although nivolumab-ipilimumab had been approved and was in our last recommendation for patients with BRAF-mutated melanoma, we didn't really know whether they should receive BRAF/MEK inhibitors, which were also approved, versus nivolumab-ipilimumab as their initial therapy. And so in the past few years, we saw the results of the DREAMseq trial, which randomized patients with BRAF-mutant melanoma to either nivolumab-ipilimumab, followed by BRAF-MEK inhibitor progression, versus the converse sequence. And we saw that at two years, the starting with a nivolumab-ipilimumab had a 20% improvement in two-year overall survival. This prompted the NCCN to change their guidelines to list nivolumab-ipilimumab or other immunotherapies as a preferred frontline therapy. And we thought that this data was important enough and somewhat validated by a randomized phase II trial, the SECOMBIT, which had a lot smaller numbers to encourage us to change the guidelines. Other minor things that we did were to take T-VEC and no longer recommend that as an option for patients with BRAF-wild type disease who had progressed on anti-PD-1 therapy and that ipilimumab and ipilimumab-containing regimens were no longer recommended for patients with BRAF-mutated disease after progression on other immunotherapy. We felt that those patients probably are best served to get BRAF/MEK inhibitors. Brittany Harvey: It's good to have clarity on some of those sequencing options for patients and also on which treatments are working better for patients in these subpopulations. So then, Dr. Sondak, the last set of recommendations. What has changed regarding options available for patients with noncutaneous melanoma?  Dr. Vernon Sondak: There's no question that our patients with noncutaneous melanomas, such as uveal melanoma or mucosal melanoma, have many fewer options and haven't benefited as much from the revolution in treatment that we've seen with our cutaneous melanoma patients, but there have been definite improvements and progress. The full update incorporates new recommendations for uveal melanoma that were published in 2022 as a rapid recommendation update, specifically a new drug called tebentafusp, which is restricted to HLA-A*02:01-positive patients. It's HLA-type restricted, but it is active in patients with metastatic uveal melanoma. And so the new guideline is that previously untreated patients with metastatic uveal melanoma who are HLA-A*02:01-positive should be offered tebentafusp as a treatment option. So that means all our patients with metastatic uveal melanoma should get HLA typed, so they know if they're a person who is eligible for this treatment and it should be considered early on in the treatment paradigm. Brittany Harvey: Well, thank you both for reviewing the updates to these evidence-based recommendations. There's a lot that's new in this field.  So then, Dr. Atkins, what is the importance of this guideline? And in your view, how will it impact clinicians, and also how will these guideline recommendations affect patients? Dr. Michael Atkins: Sure. Well, we have new treatments such as relatlimab and tebentafusp that are available and should be offered to appropriate patients, and new data on how to optimally apply previously approved treatments such as nivolumab-ipilimumab in patients with BRAF-mutated or resected stage IV melanoma, pembrolizumab use in the neoadjuvant setting, and nivo and pembro in earlier stage disease. And with this new information out there and included in the guidelines, hopefully, this will allow practitioners to give the best possible treatments to their patients, and patients to receive treatments which will improve their outcomes. Brittany Harvey: Absolutely. It's great to have new data to better inform treatment options for patients with melanoma.   So then, finally, Dr. Sondak, what are some of the most pressing outstanding questions regarding systemic therapy for patients with melanoma that may need to be addressed in a future guideline update? Dr. Vernon Sondak: Every advance brings up new questions. In neoadjuvant therapy, we have single-agent pembrolizumab with strong data from the randomized trial I spoke about. We anticipate more data about combination immunotherapy, specifically low-dose ipilimumab and nivolumab in the setting of neoadjuvant therapy. There are some trials going on with that. The best neoadjuvant treatment, the best sequence, how long should we treat, and even should we change the surgery based on the results of neoadjuvant therapy, not just the surgery, but the postoperative adjuvant therapy? Those are all questions that are key in the neoadjuvant side.  In the adjuvant therapy side, we have much more clarity now about BRAF versus immunotherapy in unresectable disease, but we still don't know always what's the best adjuvant therapy for our BRAF-mutated patients. That's an area we hope will eventually get more clarity, but I think it's going to take a while for that.   And finally, we'll learn more about the optimum sequencing of patients with metastatic disease, but especially for the patients who've already failed adjuvant or neoadjuvant therapy. So much of the data that Dr. Atkins and I talked about in metastatic disease, whether cutaneous or noncutaneous, involved previously untreated patients. But so many of our metastatic disease patients today have come to us already with some form of treatment in the adjuvant or neoadjuvant setting. We still have a lot of work to do to define the best treatment strategies for those patients.  Brittany Harvey: Definitely. Well, we'll look forward to learning more as new data comes out and as some of that research comes to fruition. So I want to thank you so much for your work to update this guideline and thank you for your time today, Dr. Sondak and Dr. Atkins. Dr. Vernon Sondak: Thank you. Dr. Michael Atkins: You're very welcome. Thanks a lot. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/melanoma-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

El Dr. Jorge A. Alatorre, oncólogo médico adscrito al Centro Médico ABC en la Ciudad de México, México, charlará en este segundo episodio de “Cáncer de pulmón en contexto” sobre el estudio NADIM II y el uso de la neoadyuvancia en pacientes con etapa III. Como invitado se encuentra el Dr. Mariano Provencio, oncólogo médico, Jefe del Servicio de Oncología Médica en el Hospital Puerta de Hierro, Madrid, España. El estudio NADIM II es un fase II, abierto, aleatorizado, de dos brazos, que evaluó el uso neoadyuvante de la quimioterapia (QT) + inmunoterapia vs. la QT sola en pacientes con cáncer de pulmón de células no pequeñas (CPCNP) localmente avanzado (etapa IIIA y IIIB) y potencialmente resecable. Recibieron 3 ciclos de nivolumab (360 mg) + QT y después de 3 ciclos, los pacientes se operaron y recibieron 6 ciclos de tratamiento adyuvante con nivolumab. Este estudio se centró en la búsqueda de la respuesta patológica completa y respuesta patológica mayor en este grupo de pacientes.  Los expertos, con base en evidencia científica y en su experiencia, contestan a las siguientes interrogantes: 1. ¿Por qué se enfocaron en los pacientes en etapas III en este estudio de NADIM II? 2. ¿Qué características deben tener los pacientes para un mayor beneficio con este esquema? 3. ¿Por qué hicieron evaluación del mediastino al inicio y al término del tratamiento con QT + inmuno? 4. El esquema de tratamiento utilizado en el estudio ¿beneficia a algún grupo en específico de pacientes? 5. ¿Cuál considera que es el futuro de los tratamientos neoadyuvantes y adyuvantes en esta neoplasia? Fecha de grabación: 6 de mayo de 2023. 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.

On episode #29 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the weeks of 5/11 – 5/23/23. Hosts: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of Puscast! Links for this episode Harmonie phase IIIb study trial results of nirsevimab against RSV lower respiratory tract infection hospitalization for infants (ESPID) Mogamulizumab for treatment of HTLV-1 associated Myelopathy/Tropical Spastic Paraparesis (IDSA) Revised protocol for secondary prevention of congenital cytomegalovirus infection with valaciclovir (IDSA) Increase in false positive fourth generation HIV tests in patients with COVID-19 (CID) Implementation of an antibiotic stewardship initiative in a large urgent care network (JAMA) Clindamycin + vancomycin versus linezolid for treatment of necrotizing soft tissue infection (OFID) Assessing empiric antimicrobial therapy with the dundee classification for skin and soft tissue infections (OFID) Combination of amoxicillin 3000mg and probenecid vs 1500mg amoxicillin monotherapy for treating syphilis in patients with HIV (CID) The sympathetic nervous system is necessary for development of CD4+ T cell memory following Staphylococcus aureus infection (JID) Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with infections caused by Acinetobacter baumannii-calcoaceticu complex (The Lancet) First reported US cases of tinea caused by Trichophyton indotineae (CDC) How to use direct microscopy for diagnosing fungal infections (CMI) Limited Cutaneous Leishmaniasis as Ulcerated Verrucous Plaque on leg (EID) Can Ivermectin kill Sarcoptes scabiei during the molting process? (PLOS) The Infectious Diseases Specialist, at risk of extinction (JID) Ticks harbor and excrete chronic wasting disease prions (NIH) Music is by Ronald Jenkees

 Continuing the conversation series, “The Edges in the Middle,” presented in collaboration with UC Berkeley's Othering and Belonging Institute, For The Wild is delighted to share Báyò Akómoláfé in conversation with Indy Johar of Dark Matter Labs. Speaking on the theme “A New Theory of the Self,” Báyò and Indy dive into the milieu of life forms entangled together on earth. The conversation asks listeners to reconsider the objective nature of self and the word around us that has been so deeply ingrained within the architecture of society. Rejecting these notions of completion and singularity, Báyò and Indy engage in a conversation that calls attention to the aliveness of the world, to the agency and intelligence of our entangled minds, and to life as an ongoing process. How might we move beyond constraining ideas of order, power, and control in order to recognize and take part in relational ecological emergence?“The Edges in the Middle” is a series of conversations between Báyò Akómoláfé and thought companions like john a. powell, V, Naomi Klein, and more. These limited episodes have been adapted from Báyò's work as the Global Senior Fellow at UC Berkeley's Othering & Belonging Institute. In this role, Báyò has been holding a series of public conversations on issues of justice and belonging for the Institute's Democracy & Belonging Forum, which connects and resources civic leaders in Europe and the US who are committed to bridging across difference to strengthen democracy and advance belonging in both regions and around the world. Báyò's conversations encourage us to rethink justice, hope, and belonging by sitting amidst the noise, not trying to cover it up with pleasant rhythms. To learn more about the Democracy & Belonging Forum, visit democracyandbelongingforum.org.   Music by Sitka Sun, generously provided by The Long Road Society Record Label. Visit our website at forthewild.world for the full episode description, references, and action points.Support the show

Twitter Gościa: https://twitter.com/ad_zimny/ Specjalnie dla Słuchaczy podcastu VotumFM mamy dla Was kod promocyjny dzięki któremu otrzymujecie 10% zniżki na wszystkie pozycje w księgarni Capitalbook. Kod: votum10 Możesz uzyskać dostęp do Strefy Premium⁠ https://votum.fm/PREMIUM/⁠, a tym samym do: ✅ przedpremierowych wywiadów, ✅ rozmów po zakończonej transmisji bez oczekiwania na premierę ✅ ekskluzywnych wywiadów zrealizowanych w 2023 roku ✅ telefonu do studia w trakcie audycji na żywo. Decydując się na subskrypcję PREMIUM wspierasz jednocześnie niezależny, prawicowy podcast VotumFM w rozwoju. Dzięki Tobie będziemy mogli produkować i transmitować jeszcze więcej audycji.

In this continuation of the third Captain's Sparchives, Fode and Alan provide classic sports radio commentary for the Rise of Phoenix 2023 tournament! Find the video footage using the link below and watch right along with us, or turn on just the audio for an old-school experience like the great boxing radio of yesteryear while you get other life done. Thank you as always for listening, subscribing, and sharing SMAFcast! WATCH THE FIGHTS HERE: Rise of Phoenix: Kessel Run SupercutFind the whole tournament here:Rise of Phoenix 2023 PlaylistPhoenix Saber Academy on SMAF website:PHXSA Official SMAF PagePhoenix Society of Historical Swordsmanship (thank you for hosting!):PSHS Official SiteWant an awesome kobodu-style display for your sabers or other martial arts memorabilia? Visit:Living Force Customs on IG(direct message or email livingforcecustoms@gmail.com for custom orders and inquiries)

W korespondencji również omówienie niekorzystnych dla rządzącej Partii Konserwatywnej wyników cząstkowych wyborów lokalnych.

Osmanlı döneminin son genel seçimi Aralık 1919'da, ülkenin bir kısmı fiilen işgal edildiği için ancak 15 vilayet, 35 mülhak liva ve 16 müstakil livada yapılabildi. Seçim yapılamayan önemli merkezler Mondros Mütarekesi'nden sonra işgal edilen Musul, Beyrut, Suriye ve Halep gibi vilayetler, Kars, Ardahan, Batum sancaklarıydı. İşgal Güçleri İzmir, Adana, Urfa ve Antep'de seçimlere önce izin vermiş sonra yasaklamıştı. İşgal Güçlerinin karargâhının olduğu İstanbul'da ise seçimler serbestçe yapılmıştı.

This message is brought to you by the Senior Pastor of the global, multicampus ministry, Petra Christian Centre, Pastor Ayo Ajani. --- Send in a voice message: https://podcasters.spotify.com/pod/show/official-ayo-ajani/message

This message is brought to you by the Senior Pastor of the global, multicampus ministry, Petra Christian Centre, Pastor Ayo Ajani. --- Send in a voice message: https://podcasters.spotify.com/pod/show/official-ayo-ajani/message

Olá, seja muito bem-vindo ao StandardsCast EP #200 A330/A350. Neste episódio conversamos com Arthur Lechmann (Coordenador de Flight Standards A330/A350) sobre o sistema SLS embarcado em nossos A350 e a certificação CAT III para esta frota, abordamos a remoção da política de aceleração a 400ft e trouxemos algumas atualizações no FCOM A330/A350. Em caso de dúvidas, críticas ou sugestões, envie um e-mail para standardscast@voeazul.com.br. Este Podcast foi produzido pela Diretoria de Operações da Azul Linhas Aéreas. Em caso de divergência entre qualquer assunto técnico abordado e os documentos oficiais, os documentos prevalecerão. Todos os direitos reservados.

Interferometric imaging of the type IIIb and U radio bursts observed with LOFAR on 22 August 2017 by Bartosz Dabrowski et al. on Thursday 24 November The Sun is the source of different types of radio bursts that are associated with solar flares, for example. Among the most frequently observed phenomena are type III solar bursts. Their radio images at low frequencies (below 100 MHz) are relatively poorly studied due to the limitations of legacy radio telescopes. We study the general characteristics of types IIIb and U with stria structure solar radio bursts in the frequency range of 20 - 80 MHz, in particular the source size and evolution in different altitudes, as well as the velocity and energy of electron beams responsible for their generation. In this work types IIIb and U with stria structure radio bursts are analyzed using data from the LOFAR telescope including dynamic spectra and imaging observations, as well as data taken in the X-ray range (GOES and RHESSI satellites) and in the extreme ultraviolet (SDO satellite). In this study we determined the source size limited by the actual shape of the contour at particular frequencies of type IIIb and U solar bursts in a relatively wide frequency band from 20 to 80 MHz. Two of the bursts seem to appear at roughly the same place in the studied active region and their source sizes are similar. It is different in the case of another burst, which seems to be related to another part of the magnetic field structure in this active region. The velocities of the electron beams responsible for the generation of the three bursts studied here were also found to be different. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2211.12756v1

Interferometric imaging of the type IIIb and U radio bursts observed with LOFAR on 22 August 2017 by Bartosz Dabrowski et al. on Wednesday 23 November The Sun is the source of different types of radio bursts that are associated with solar flares, for example. Among the most frequently observed phenomena are type III solar bursts. Their radio images at low frequencies (below 100 MHz) are relatively poorly studied due to the limitations of legacy radio telescopes. We study the general characteristics of types IIIb and U with stria structure solar radio bursts in the frequency range of 20 - 80 MHz, in particular the source size and evolution in different altitudes, as well as the velocity and energy of electron beams responsible for their generation. In this work types IIIb and U with stria structure radio bursts are analyzed using data from the LOFAR telescope including dynamic spectra and imaging observations, as well as data taken in the X-ray range (GOES and RHESSI satellites) and in the extreme ultraviolet (SDO satellite). In this study we determined the source size limited by the actual shape of the contour at particular frequencies of type IIIb and U solar bursts in a relatively wide frequency band from 20 to 80 MHz. Two of the bursts seem to appear at roughly the same place in the studied active region and their source sizes are similar. It is different in the case of another burst, which seems to be related to another part of the magnetic field structure in this active region. The velocities of the electron beams responsible for the generation of the three bursts studied here were also found to be different. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2211.12756v1

Marco Pautassopresidente Progetto Cantoregi"Biblioteche in Festa"A Racconigi e Savigliano arriva la prima edizione di “Biblioteche in Festa”Il 24 e 25 settembre prossimi un caleidoscopico intreccio di eventi culturali promosso da Le Terre dei Savoia e da Progetto Cantoregi. Tra gli ospiti anche Davide Longo, Lella Costa e Giusi MarchettaLa lettura come straordinaria leva per la crescita individuale e come imprescindibile motore dello sviluppo di una società. Le biblioteche, allora, come luoghi della conoscenza e del sapere da valorizzare e da proteggere per il loro ruolo comunitario. Questa, in breve, la filosofia della prima edizione di Biblioteche in Festa, il nuovo format culturale ideato e promosso dall'Associazione Le Terre dei Savoia e da Progetto Cantoregi in collaborazione con la Direzione regionale Musei Piemonte, il Castello di Racconigi e i Comuni di Racconigi e Savigliano, con il patrocinio dell'Associazione Italiana Biblioteche, del Dipartimento di Filosofia e Scienze dell'Educazione dell'Università di Torino, del Centro Studi Piemontesi e con il sostegno delle Fondazioni Cassa di Risparmio di Torino, Cuneo, Savigliano e Fossano. Sabato 24 e domenica 25 settembre prossimi saranno quindi tanti gli eventi organizzati tra Racconigi e Savigliano, per una due giorni che intende da un lato promuovere la lettura e le sue declinazioni (sabato) e dall'altro favorire il confronto e la riflessione tra gli operatori del settore (domenica). Ad inaugurare la kermesse sabato 24 settembre alle ore 10.30 nella Sala Conferenze del Castello Reale di Racconigi, sarà la presentazione del progetto Letture al Castello promosso dall'Associazione Le Terre di Savoia in collaborazione con +Cultura Accessibile Onlus con il sostegno della Fondazione Cassa di Risparmio di Cuneo. Un appassionante percorso di avvicinamento al mondo delle fiabe che ha coinvolto i ragazzi di III A e della III B della scuola primaria Luigi Ornato di Caramagna Piemonte, abili a creare e a registrare due fiabe originali sulla falsariga dei modelli di Esopo e di Lorenzo Pignotti.A seguire, sempre nel Castello di Racconigi con partenze alle ore 11.00, 11.30 e 12.00, Iter in Hortis, ideato dal Progetto Cantoregi: un percorso di letture ad alta voce (con le attrici e gli attori Annalisa Aragno, Irene Avataneo, Alessio Giusti, Manlio Pagliero), dedicato alla passione per i libri, che si svilupperà tra la Biblioteca di Carlo Alberto e il parco del Castello di Racconigi con annessa performance musicale di Simona Colonna (euro 2 a persona). Nel pomeriggio spazio alle presentazioni letterarie con Marco Pautasso in dialogo con Giulia Ajmone Marsan (Aniceta & Edoardo. Le famiglie Frisetti e Agnelli agli esordi dell'imprenditoria torinese, Centro Studi Piemontesi, ore 15.30), Alberto Chiara e Luciano Regolo (Maria José, regina indomita sul golpe ordito nel settembre 1938 al Castello di Racconigi contro Mussolini, Ares Edizioni, ore 17.00) e Davide Longo in dialogo con Livio Partiti (La vita paga il sabato, Einaudi Editore, ore 18.00). Alle ore 21.00 presso il teatro Milanollo di Savigliano, invece, appuntamento con Lella Costa e il reading Stanca di guerra, tratto dall'omonimo spettacolo del 1996 scritto da Lella Costa, Alessandro Baricco, Sergio Ferrentino, Massimo Cirri, Piergiorgio Paterlini e Bruno Agostani per la regia di Gabriele Vacis (ingresso euro 10; ridotto over 65 e under 18 euro 8).Nella giornata di domenica sarà la sede di Savigliano del Dipartimento di Filosofia e Scienze dell'Educazione dell'Università di Torino a fare da cornice ad alcuni momenti di approfondimento dedicati al settore librario. Comincerà Chiara Faggiolani (autrice de Le biblioteche nel sistema del benessere) alle 11.30 in dialogo con Maurizio Vivarelli e Cecilia Cognigni, prima del brunch presso il Caffè Intervallo di Savigliano a cura di Voci Erranti Onlus (ore 13.00). Nel pomeriggio alle ore 14.30 l'incontro Le biblioteche della provincia di Cuneo si raccontano tra prospettive, progetti e speranze, quindi il convegno “Le biblioteche come motore della promozione della lettura” (ore 16.00) con, tra gli altri, Paola Baioni, Enzo Borio, Cecilia Cognigni, Monica Monasterolo, Valeria Nigro, Maurizio Vivarelli, Lucetta Paschetta. A chiudere la giornata, infine, la lectio magistralis Lettori si cresce di Giusi Marchetta alle ore 17.30. Una prima edizione che intende divulgare il piacere della conoscenza e della consapevolezza, favorendo incontri eterogenei tra lettori e scrittori, appassionati e professionisti. Una manifestazione che parla all'intero territorio, con la volontà di costruire una rete di eccellenze letterarie diffuse che possano diventare motore di sviluppo comunitario ed elemento di attrattività turistica. La presenza all'evento prevede il rilascio di un attestato di partecipazione per gli usi consentiti dalla legge. Sarà inoltre rilasciato ai bibliotecari l'attestato di partecipazione da parte dell'Associazione Italiana Biblioteche – Sezione Piemonte.IL POSTO DELLE PAROLEascoltare fa pensarehttps://ilpostodelleparole.it/

Estratto dall'incontro tra il prof. Barbero e i ragazzi della classe III B del Liceo Classico "D. Borrelli" di Santa Severina. Il tema dell'incontro è il romanzo "Le ateniesi" (A. Barbero - 2015, Mondadori): https://amzn.to/3Rb6J8pFonte: https://www.youtube.com/watch?v=QewysLXEpRY --- // Disclaimer // Tutti gli audio disponibili sono utilizzati negli episodi dopo previo consenso e accordo con i distributori originali di altre piattaforme e/o comunque distribuiti liberamente e originariamente con licenze CC BY 4.0 e affini, viene sempre riportata la fonte. I titoli potrebbero differire in caso di titoli troppo lunghi. Per qualsiasi dubbio o problema contattateci PER FAVORE prima alla nostra mail: flamsteed46[@]gmail[dot]com

This week's Fact & Fiction in The Conjuring Universe is the conclusion to the Perron family hauntings and sightings that occurred in their secluded Rhode Island farmhouse. We've got plenty of creepy encounters and one big seance left to finish up this story! Our sources for this episode are House of Darkness, House of Light by Andrea Perron, Open Minds with Regina Meredith on Gaia, and Correcting the Conjuring House History by Kenny Biddle. Also, check Mike out as a guest on this weeks EPISODE 17 of Staging A Podcast! Follow and drop us a line on the most evil Instagram and Facebook. WE WANT TO HEAR YOUR GHOST STORIES! Send us an email at lastthreerowsofhorror@gmail.com Thank you for listening and supporting LAST THREE ROWS OF HORROR!

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.     

In this episode Hina & Sandeep are joined by Lukas Brockmann, analyst on Action. Listen how a value discounter in Benelux, with improving geographical diversification supports earnings resilience.

Guest host Dr. Nathan Pennell, of the Cleveland Clinic Taussig Cancer Institute, and Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, discuss the ATLANTIS trial and other novel therapies in advanced SCLC, NSCLC, and malignant pleural mesothelioma featured at the 2022 ASCO Annual Meeting Poster Sessions.  Transcript   Dr. Nathan Pennell: Hello, I'm Dr. Nathan Pennell, your guest host for the ASCO Daily News Podcast, today. I'm the co-director of the Cleveland Clinic Lung Cancer Program and vice-chair of Clinical Research for the Taussig Cancer Institute.  My guest today is my friend Dr. Vamsidhar Velcheti, an associate professor and medical director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone Health.  We'll be discussing key posters on lung cancer that will be featured at the 2022 ASCO Annual Meeting. Although the oral sessions tend to get the most press, we want to make sure you don't miss out on some high-impact abstracts that are presented in the poster session.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.orgpodcasts.  Vamsi, it's great to speak with you today.  Dr. Vamsidhar Velcheti: Thank you, Nate. It's a pleasure to discuss these 5 outstanding abstracts.  Dr. Nathan Pennell: Why don't we start with Abstract 9021, “Genomic correlates of acquired resistance to PD-(L)1 blockade in patients with advanced non—small cell lung cancer (NSCLC).” Vamsi, what were your key takeaways from this study?  Dr. Vamsidhar Velcheti: This is an important study in my opinion. This was a very large study of 1,700 patients from Dana Farber and the investigators looked at 45 specimens and matched pre- and post- immunotherapy treated patients. And they looked at the data mechanisms of resistance that were identified in 25 out of the 45 patients, that is 55% of the patients.  5 patients had acquired STK11 mutations. One patient had a KEAP1 alteration. There were several patients who had like KEAP1 SMARCA4 mutations. And interestingly, there were also some patients who developed KRAS-G12C mutation as well on the post-treatment specimens.  So, this is an interesting abstract. We typically don't do biopsies on patients progressing on immunotherapy. At this point, we don't have a standard clinical indication to do so. However, identifying these new novel mechanisms of genomic mechanisms of resistance is actually very important, because a lot of new therapy medications are being developed to target, for example, KEAP1, and could be approached to target microglobulin mutations. So, it's very important to kind of understand the mechanisms of resistance.  Dr. Nathan Pennell: Yeah, I completely agree. I mean, most of the benefits in second line in the refractory setting with targeted treatments came about through studies like this where there was broad sequencing of resistance and trying to understand and I think we're still kind of in the infancy of understanding resistance to immunotherapy, but it's a good start.  Abstract 9019 was another interesting study in non—small cell lung cancer. That was “A phase II study of AK112 (PD-1/VEGF bispecific) in combination with chemotherapy in patients with advanced non—small cell lung cancer.” Can you tell us a little bit about that study?  Dr. Vamsidhar Velcheti: Yeah, this is a multicenter phase-2 trial. This is an interesting agent. It's a PD-1/VEGF bispecific antibody developed by Akeso Bio. This is a single-arm study, and they did the study in 3 different cohorts.  One of the cohorts was patients with advanced non—small cell lung cancer who had wild-type EGFR/ALK, and they were treatment-naive. There was another cohort of patients where they enrolled patients with EGFR mutation who developed resistance to EGFR tyrosine kinase inhibitors (TKIs) and essentially progressed on osimertinib. And there was another cohort where patients were enrolled who were PD-1 refractory, they had prior PD-1or PD-1 chemo combination, and they had progressions. So, they enrolled a total of 133 patients, it was a decent-sized study, but a very early efficacy finding study.  In the cohort-1 which is the cohort that is enrolled with untreated patients with advanced non—small cell lung cancer. They had like 20 partial responses out of 26 patients that were evaluable and enrolled in the cohort, and there were 6 patients who had stable disease.  So, overall, the response rate was 76.9% and 100% disease control rate. So, this is a very small cohort and small data set. So, we have to interpret this with caution. But suddenly, a very interesting signal here for this VEGF/PD-1 bispecific antibody.  Dr. Nathan Pennell: The 40% response rate in the immunotherapy (IO) and chemo refractory patients, I thought was fairly interesting, although, as you said, very small numbers in these cohorts will have to be reproduced in larger trials.  Dr. Vamsidhar Velcheti: Right. I think there was a lot of excitement early on the IMpower150, right? With the combination of bevacizumab with chemo-theralizumab.  There seems to be some signal in terms of the addition of a VEGF inhibitor to immunotherapy. And we've seen that consistently in renal cells and other tumor types. So, I think this is a really intriguing signal. I think this definitely warrants further exploration.  So, the other interesting thing was cohort-2 where they enrolled patients who had progressed on EGFR TKIs. So, in that cohort, they had like 19 evaluable patients and 13 patients had a partial response and 5 had stable disease. So, a very respectable response rate of 68.4% and 94.7 disease control rate. So, again, very small numbers, but a nice signal here for the efficacy of the drug.  There was another cohort, which is the cohort-3 where they enrolled patients who progressed on PD-1 therapy, and they enrolled a total of 20 patients with 8 patients having a partial response, following progression on PD-1 therapy.  Dr. Nathan Pennell: Yeah, I look forward to seeing further follow-up on this. It definitely sounds interesting. Moving on to Abstract 8541. This was “Durvalumab (durva) after chemoradiotherapy (CRT) in unresectable, stage III, EGFR mutation-positive (EGFRm) NSCLC: A post hoc subgroup analysis from PACIFIC,' which of course was the study that led to the broad use of durvalumab, the anti-PD-L1 antibody after chemoradiotherapy for unresectable stage III non-small cell, but this was the post hoc subgroup analysis of the EGFR mutation-positive group. And this is a subgroup we've really been curious about whether there was a role for consolidation, immunotherapy, or not. And so, what are your thoughts on the study?  Dr. Vamsidhar Velcheti: I agree with you, Nate, that this is actually some data that I was really, really looking forward to. Before we actually talk about the abstract. What do you do for those patients? If you have an EGFR mutation patient who has stage IIIB, what do you do right now?  Dr. Nathan Pennell: It's a great question. I have a discussion with them about the potential pluses and minuses of doing consolidation durvalumab. But I actually don't always use durvalumab in this setting, because of concerns about if you're using durvalumab and they recur, perhaps there is a problem with toxicity with using osimertinib. Honestly, I go back and forth about what the right thing is to do in this subgroup.  Dr. Vamsidhar Velcheti: No, I think that's the right context. I think that's a good setup to kind of discuss the data from the trial. I'm really excited about this. And I'm glad that we have this data to look at.  So, as you pointed out, the Pacific trial, its U.S. Food and Drug Administration (FDA) approval for durvalumab in the consolidation setting for patients with stage III after chemoradiation. This has now been the standard of care for like a few years now. The problem with the study is that patients with EGFR/ALK were allowed to enroll in the study.  Typically, for most IO trials, we generally tend to see patients with EGFR/ALK being excluded. So, this trial was an exception. In this study, they actually presented a post-hoc exploratory analysis of efficacy and safety of patients who did consolidation with durvalumab, but there was a total of 35 patients of the 713 patients that were randomized in the trial. And out of the 35 patients with EGFR mutation, 24 received durvalumab and 11 received a placebo.  So, of course, you're going to interpret this data with a little bit of caution. This is a full stock analysis, not pre-planned in small numbers. In this dataset, essentially, the median progression-free survival (PFS) was not different among patients treated with durvalumab or placebo, and the median survival was also not statistically significant. Overall, there was not much benefit from adding durvalumab in this setting in patients who have EGFR mutation-positive stage III lung cancer.  Dr. Nathan Pennell: I think that tends to track along with what we who have been treating patients with EGFR mutations for years, and knowing the disappointing response rates, certainly in the advanced stage with immunotherapy, I think we were concerned that in this consolidation phase that it would also potentially be a relatively marginal benefit. I agree with you that 35 patients are too small to make any definitive conclusions, but it certainly isn't supportive of a large benefit.  Dr. Vamsidhar Velcheti: But I think I'm excited about the LAUREL study that's ongoing, hopefully, that'll give us a little bit more definitive answers as to what we should be doing for patients with EGFR mutation-positive disease. Suddenly this is a piece of information that's helpful for treating physicians to make some decisions on clinical management for these patients.  Dr. Nathan Pennell: I agree. Now moving beyond the non—small cell. Let's talk about “Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM).” That's Abstract 8561. What were your takeaways here?  Dr. Vamsidhar Velcheti: Yeah, it's always good to see some new therapeutic options for patients with mesothelioma. This is somewhat of an orphan disease and we haven't seen a lot of advances. Granted, we have some new therapeutic options with immunotherapy now, like, there is now a standard of care in the frontline setting.  So, this particular approach with ONCOS-102 is an oncolytic adenovirus expressing GM-CSF. And this is intended to stimulate the local and systemic immune response and remodulate the tumor microenvironment.  This was a small phase 1 study where they had a CFT run-in of 6 patients and a total of 25 patients were randomly assigned to receive ONCOS-102 intratumorally with ultrasound guidance or CT guidance and they injected this oncolytic virus into the tumor directly.  They were also getting treatment with platinum pemetrexed which is the standard of care in the frontline setting. The control here was 6 cycles of platinum pemetrexed. So, they enrolled both the treatment-naive patients in the frontline setting and they also enrolled patients who will progress on a platinum doublet.  I should note that none of these patients were treated with immunotherapy. I think that's something that we'll kind of get back to and we'll discuss. Overall, from a safety standpoint, there were some expected toxicities like pyrexia and nausea which is seen in the experimental group. It's just kind of to be expected with an oncolytic virus. Overall, the 30-month survival rates were 34.3% and 18.2% in the control arm, and the median overall survival (OS) was 19.3 months and 18.3 in the controller.  So, for patients who were treated with the frontline chemotherapy, the survival rate was better with 30 months survival, it was 33.3 [months]. And in the experimental group, it was 0%.  So, overall, they also looked at tumor-infiltrating lymphocytes, they had CD4 around CD8 and granzyme B expressing CDA T-cells, and they had favorable PK from increased immune cell infiltration. So, this is very promising data but of course in a small study, and also in a population that hasn't had immunotherapy patients who are getting platinum doublet. In terms of safety, I think it looks promising. We need to see larger studies, especially with immunotherapy combinations.  Dr. Nathan Pennell: Yeah, I was impressed with the increased tumor infiltration of CD4 and CDA-positive T-cells, and the survival in the first line looked fairly impressive, although again, a very small subgroup of patients. But as you said, a standard of care these days is definitely going to involve immunotherapy. And so, I look forward to seeing combination trials in the future with this drug.  Shifting from mesothelioma over to small cell lung cancer, Abstract 8570 is “Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.” Do you think that this would influence how we approach patients with brain metastases in the small cell?  Dr. Vamsidhar Velcheti: There are some in the community who kind of advocate for SRS in small cells if they have limited CNS disease. Certainly, I'm not one of them, but I think this is an interesting study in that light like we have never had any proper randomized trial. And we probably won't have randomized trials in that setting. So, at the end of the day, I think we all kind of customize our treatment approaches based on our patients and how much disease burden they have.  But having said that, the authors here have done a pretty large systemic analysis, and they looked at 3,700+ trials, they looked at random effects meta-analysis pooled hazard ratios for overall survival in patients who received SRS in the whole brain with or without SRS boost.  What they found was that overall survival following SRS was not inferior to whole brain RT. What do we really make out of this data? I think, given the heterogeneity, we have to see how the analysis was done and the kind of studies that went into the analysis. But however, I think the bigger question is, is there a population that we need to maybe—perhaps like, if somebody has an isolated brain met, you could potentially consider SRS with a whole brain RT for better local control.  So, the authors actually look at pooled data to look at local control versus intracranial distant control. So, this is a really interesting approach that asks the question, if patients had SRS and whole brain radiation, would it actually offer adequate intracranial distant control meaning like, do they develop new lesions?  So, it does look fairly decent. But again, it all depends on what kind of studies went into the analysis. And I don't think we should read too much into it. But at the same time, it kind of raises the question: is there a population of patients with small cell where it may be potentially appropriate to give SRS?  So, that's what I do in my day-to-day clinical practice. Sometimes there are situations where you kind of do the thing that we don't usually always do like in the small cell, we always think about whole brain radiation as something that we always have to offer, but I want to hear your perspectives too.  Dr. Nathan Pennell: No, I was always taught that you never did anything with whole brain radiation in the small cell even with a solitary metastasis. For a study like this, it's certainly interesting. You wonder how much selection bias there was towards people with fewer brain metastases and perhaps being in better health or better response to systemic disease that were referred for SRS, compared to whole brain radiation.  Part of the issue is the morbidity associated with whole brain radiation is significantly more than with SRS. And now that we are starting to, for the first time, see some patients with small cell [lung cancer] that are living substantially longer with immunotherapy, it might be worth exploring which patients might benefit from having that lower morbidity from whole brain radiation. But I agree with you that I'm not sure that we know who those patients are.  Dr. Vamsidhar Velcheti: Yeah, I think this is a difficult question to answer through a meta-analysis in my opinion. But having said that, your thought in terms of proving systemic therapies, then we kind of revisit the paradigm of offering SRS to some patients may be, especially with new BiTE T-cell engager studies that are ongoing, and hopefully, if you see some positive results, that might change what we do, but it's an important clinical question.  Dr. Nathan Pennell: And finally, in Abstract 8524, we have an interesting analysis of patients with relapsed small cell lung cancer, who received single-agent Lurbinectedin in the phase-3 Atlantis trial. What do you think about this poster, and why should this be on our radar?  Dr. Vamsidhar Velcheti: Yeah, I think this has been an interesting approval, of course, lurbinectedin FDA approved, as you know, like in June of 2020, based on data from a trial that uses 3.2 milligrams per meter square dosing every 21 days in second line setting post-chemotherapy.  What happened after that was there was a trial with the combination with doxorubicin in the second line setting comparative arm in that phase 3 trial topotecan or CAV.  In that trial, it was a negative trial, the primary endpoint was not met. The primary endpoint was overall survival, and it was a negative trial. And there were subgroup analyses done in the trial. The study that is presented now is actually a post-hoc analysis looking at patients who received treatment with this combination with doxorubicin that is like a lurbinectedin with doxorubicin, who had like a total of 10 cycles of the combination, and they switched to lurbinectedin monotherapy.  So, there were a total of 50 patients in that trial. They looked at the responses and the durability of responses in that population. It's a highly select population that made it to 10 cycles and they had stable disease or better and they switched to lurbinectedin monotherapy.  So, the highlight of the abstract is the median overall survival was 20.7 months. Of course, for small cell, that's really impressive. But I think we've got to be really careful in interpreting this data. This is like a small subgroup of highly selected patients who actually benefited from the trial. My question for you, Nate, is do you use lurbinectedin in the second line setting frequently or are you still treating them with topotecan?  Dr. Nathan Pannell: We still often use topotecan. I think lurbinectedin certainly seems to be an active drug, and it has some favorable schedule of administration pretty well tolerated from a tolerability standpoint, but from an efficacy standpoint, I still haven't really seen much that makes it stand out as significantly better than older options like topotecan or irinotecan.  That being said, it is intriguing that there is a subgroup of people who seem to have prolonged disease control with this. The problem, of course, is if you already select the people who make it 10 cycles without progression, then you're already picking the group of people who are doing extremely well. So, it's not surprising that they would continue to do extremely well.  Nonetheless, it's a sizable subgroup of people that seem to benefit and it would really be nice if there was, for example, a biomarker that might tell us which patients would truly benefit from this drug compared to our other options.  Dr. Vamsidhar Velcheti: Yeah, exactly. True. Right, I mean, like all of us have patients who have done exceedingly well on topotecan and I had a patient on paclitaxel for years. So, it's really important to kind of keep that in mind when we look at these sub-proof post hoc analyses.  Dr. Nathan Pennell: Well, thanks Vamsi for sharing these important advances in lung cancer that will be featured at the 2022 ASCO Annual Meeting.  Dr. Vamsidhar Velcheti: Thank you, Nate.  Dr. Nathan Pennell: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.    Disclosures:  Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Vamsidhar Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine , AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen  Research Funding (Institution): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  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.   

I'm so excited for you to hear from the beautiful, Catrina Crutcher.  She was diagnosed on June, 15, 2021 with triple negative breast cancer stage IIIB. She also have the BRCA1 gene mutation. Her treatment plan has consisted of sixteen rounds of chemotherapy, bilateral mastectomy with tissue expanders and fourteen lymph nodes removed.  As of January 31, 2022, she's had a 100% complete pathological response. Connect with Catrina here -> https://www.instagram.com/catrina_fighterwithfaith/ MY favorite Luxury, organic, completely clean skincare line: http://www.kpsessentials.com/discount/Jen10  - USE Jen10 at checkout to recieve 10% off. Get my new book here: https://www.amazon.com/dp/1685156126/ref=cm_sw_em_r_mt_dp_ZYMQ0QJ4YHRRYRY0V2DS Connect with me on Instagram: https://www.instagram.com/jendelvaux/ Email me → coachjennyd@gmail.com GROUPS TO JOIN: * STRONGER TOGETHER - Cancer group for women you can request to join: https://www.facebook.com/groups/womeninpink MY FAVORITES: To help with sleep → Sleepi Gummies: https://glnk.io/z2pl/jendelvaux15 * Pique Tea: Favorite Tea-> https://www.piquetea.com/?rfsn=5818415.d1d969a&utm_source=affiliate * ORGANIFI CODE TO GET DISCOUNT:  https://www.organifishop.com -> Use JEND at check out to save 15% off. * Mid-Day Sqaures!! 15% off here -> https://www.middaysquares.com/?sca_ref=858254.CbxPK42ccG - USE CODE JEN15 at checkout. * MENOPAUSE MIRACLE: https://pinklotus.com/elements/?r=401  

Dr Guerra organic chemistry notes and concepts --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

L'arôme inclassable que Barbara instille à tous ses pas, à tout ce qu'elle touche...

Disclaimer: The passage of Scripture read out loud in the beginning of each podcast episode will be in Hebrew followed by the direct translation in English from the Complete Jewish Study Bible. Come listen to DIFFERENT. - This Episode will continue from IIIb, concluding the differences between The REAL Spoken Word of ADONAI as opposed to the Rabbinical version, The Talmud and its parables, myths and legends. Also, a challenge is presented to the leaders of The Body of Messiah, which leads to the next upcoming episode dealing with Israel and her direct relationship with The Kehilah (Congregation) of ADONAI! www.hebrew4christians.com (NOT hebrew4christians.net) www.oneforisrael.org www.epidemicsound.com www.audacityteam.org --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/gadi-hyer4/support

Disclaimer: The passage of Scripture read out loud in the beginning of each podcast episode will be in Hebrew followed by the direct translation in English from the Complete Jewish Study Bible. Come listen to DIFFERENT. - In actuality Episode IV should be Episode IIIb, a continuation to my previous podcast. Here I touch on the very foundation of the Messianic faith by analyzing the heart of what Messiah Yeshua disputed and debated with the Rabbis of Israel - the critical difference between the Written Torah, The Word of God and the Oral Torah of the Pharasees and Scribes, which would become later the Mishnah & G'Marah, also known as the Talmud. Becoming familiar with this pillar of Rabbinical Judaism is crucial to learning and expanding on your faith in the Jewish Messiah! Enjoy! Please go visit www.hebrew4christians.net for more information! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/gadi-hyer4/support

Disclaimer: The passage of Scripture read out loud in the beginning of each podcast episode will be in Hebrew followed by the direct translation in English from the Complete Jewish Study Bible. Come listen to DIFFERENT. - In this three part podcast, I will present to you a brief history of Israel, various breakdowns of Hebrew words, the definition of the concept of 'church', why it is in desperate need of reuniting under one common banner and what in the world does salt have to do with any of this? If you want to find out, you'll have to wait for episode IIIb! (or is it episode 4?) --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/gadi-hyer4/support

Carolyn Cole-Rodenburg – The Truman Charities Podcast: A Community of Caring with Jamie Truman Episode 20 Carolyn Cole-Rodenburg Carolyn Cole-Rodenburg, a 18-year breast cancer survivor, is the Founder & President of The IIIB's Foundation, a highly recognized and respected breast cancer charity. She is an exemplary model of someone who has personal knowledge of the physical and emotional effects of breast cancer. Carolyn is determined to fully live her life dedicated to comforting and educating other survivors, their family and friends. She is a dynamic professional who easily communicates with all intellectual levels and shares her knowledge and compassion openly in an attempt to better educate others about important issues faced by women following a breast cancer diagnosis. Carolyn's passion is to help women! 1 month following her wedding of April 12, 2002, at the age of 43, she was diagnosed with breast cancer and underwent a double mastectomy. She survived the life-threatening disease as a result of her 1st mammogram she had due to the encouragement of friends. Her diagnosis and survival ignited a passion in her to devote her life to educate women about early detection and to provide resources and comforting items needed during the breast cancer process. She found that there were many people raising money for large corporations to help find the cure, but she felt the lack of support, emotional healing and comfort for those women who may not have time to wait for a cure. Listen to this uplifting Truman Charities episode with Carolyn Cole-Rodenburg about her charity and her determination to comfort and educate cancer survivors.  Here is what to expect on this week's show: Her IIIB's Charity donations of baskets to patients and how they comfort women with specific items inside on their journey and fight.  The importance of Breast Cancer Awareness Month. (October) How Carolyn dedicated her life to promoting recovery after breast cancer surgery and how she has been successful with her product creativity and personal insight, providing dignity and hope for women on their journey to recovery.   Connect with Carolyn: Guest Contact Info: Website: https://www.keepthecandleglowing.org/ Facebook- https://www.facebook.com/TheIIIBsFoundation/ Instagram- @theiiibs Learn more about your ad choices. Visit megaphone.fm/adchoices