Podcasts about vhl

Key Topics: 2025 Draft Breakdown Not a single Canadian goalie drafted in the top 15 of the 2025 NHL Draft. Russia had 7 goalies drafted. Czech Republic had 6. The first Canadian goalie taken was Elliott Lennon in the 4th round, and he was US developed out of prep school. The guys break down what the numbers actually mean and what they don't. The Russian Model Russia identifies top goalies around age 11-12, places them near a developmental pathway (MHL, VHL, KHL), and brings them together for centralized camps several times a year to work on shared issues. The result is ultra-athletic goalies with a built-in pro pathway. North America has no equivalent. Goalie coaches don't collaborate. There is no standardized model. What Scouts Are Actually Buying Technique is teachable at the pro level. Athleticism, skating ability, and tracking ability are not. Scouts are drafting ceiling. That means size (6-foot-1 was reportedly the smallest goalie drafted) and raw athleticism matter more than technical polish at the draft stage. The COVID Factor The 2013 Ontario goalie birth year may be the worst in provincial history. Those kids were 8-9 years old during key development years and lost roughly a season and a half of minor hockey. This draft is the first wave. It will continue for several more years before it resolves. Sports Specialization and Burnout Jamie argues that burnout doesn't come from playing too much hockey. It comes from pressure. A kid playing summer hockey as a centerman with zero stakes is not burning out. A kid in Triple A baseball under the same win-at-all-costs pressure after eight months of Triple A hockey is burning out from the mindset, not the sport. Booge adds nuance from the applied coaching side, landing on athlete-led specialization, supported by off-ice athletic development and fun-based multi-sport activity. Over-Coaching and the "Science" Trend Both coaches push back on the trend of over-analyzing goalie mechanics with biomechanical tools and angle measurements on video. Buj example: a goalie with a blocker foot slightly behind him. The fix was a simple feel-based cue. "Push your blocker foot forward. It'll feel weird. That's fine." Solved in one rep. No iPad required. The concern is analysis paralysis and coaching athletes out of their natural feel. There is also a pointed critique of making "silly" warm-up drills appear scientific for content performance. Goalie Power Skating Jamie has brought in a dedicated power skating coach for his goalie group. The result: outside edge work that exposes how over-coached most older goalies are on inversion and inside edges. The younger goalies pick it up easier. The 15-17 year olds struggle and resist. Outside edge development gets a strong endorsement for long-term skating quality and puck retrieval ability. Pad Stiffness and Glove Angle Parting shot hot take: if you are not a fast, flexible lateral skater, you should not be in a soft pad. Soft pads require the athlete to control rebounds. Stiff pads do it for you. Match equipment to your athletic profile, not brand preference. Glove break angle deserves the same consideration. Upcoming Content Tydan skate blade profile podcast (Jamie visiting with his son to test multiple profiles) Pad Skins West Michigan event in August (free gear customization day for local goalies) San Jose Sharks Stan club membership for Buj  Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

While the podcast team is taking a Radical Sabbatical, Kim is interviewing authors of the books that have had a big impact on her in the past two years. In this episode she's speaking with Tom Rath about his new book What's The Point. Graduation speeches are often filled with lofty advice for how to approach the upcoming transition from school to the real world–a topic that feels especially fraught at this moment of AI Anxiety.  Speakers often urge newly minted graduates to “follow your passion.” But is that the best way to decide what type of work to focus on as a career?  Perhaps a better approach is to figure out what the world needs and how you can best contribute. Tom Rath stresses the importance of surveying the landscape and identifying the big problems the world is facing. Then, identify your skills and develop them so that you can help address the issues that concern you.  One fascinating point Tom makes is that 90% of people in the workforce fall into roughly 50 different occupations. However, most of us are only exposed to a handful of these 50, often only what their parents or parents' friends do for a living. Wouldn't it be better to give young adults exposure to a much wider range of careers before they pursue career goals?  In fact, we could all benefit from this exposure. It's never too late to change careers. Tom Rath's CareerSight team brings together industry experts committed to helping people discover career possibilities and find purpose. Background on Tom Rath: Tom is an author and researcher who studies how careers impact health and well-being. He has written 12 books that have sold more than 10 million copies and made hundreds of appearances on global bestseller lists. Tom's first book, How Full Is Your Bucket?, was an instant #1 New York Times bestseller. His book StrengthFinder 2.0 was listed as Amazon's top-selling non-fiction book of all time. Tom's other bestsellers include Strengths Based Leadership, Wellbeing, Eat Move Sleep, and Are You Fully Charged? Tom is currently co-founder and CEO of CareerSight. He previously led Gallup's workplaces business and served as a Senior Scientist. Tom was also a Vice-Chair of the VHL cancer research organization. He is a graduate of the University of Michigan and the University of Pennsylvania, where he has also been a guest lecturer. CHAPTERS: (00:00) Introduction to Radical Sabbatical and Tom Rath's Book (01:52) The Problem with Passion (06:56) Purpose vs. Passion: Finding Meaning in Work (11:22) Job, Career, and Calling: Understanding the Differences (13:10) Shifting Focus: From What You Do to Who You Help (21:28) Skepticism About Childhood Dreams and Career Paths (24:29) Reevaluating Life Choices (28:01) Exploring Career Options (30:40) The Importance of Exploration (33:02) Navigating Career Pressures (34:40) The Evolution of Work (39:57) Understanding Comparison Detox (43:10) Finding Meaning in Daily Life Connect with the Radical Candor team: ⁠⁠⁠⁠⁠⁠Website⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠TikTok⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠LinkedIn⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠YouTube⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Bluesky⁠⁠⁠⁠ Learn more about your ad choices. Visit megaphone.fm/adchoices

What if purpose isn't something we find, but something we build? In this episode, bestselling author and researcher Tom Rath breaks down purpose in a way that feels practical, not pressuring. We talk about why “purpose” can feel loaded, how service and relationships create meaning, and simple ways to notice the impact we are already having, especially in hard seasons.Thrive Global Article: Tom Rath on Turning Purpose Into Your Daily SuperpowerExplore his books, tools, and work at TomRath.org and follow Tom on X.About Our Guest:Tom is an author and researcher who studies how careers impact health and wellbeing. He has written 12 books that have sold more than 10 million copies and made hundreds of appearances on global bestseller lists.Tom's first book, How Full Is Your Bucket?, was an instant #1 New York Times bestseller. His book StrengthFinder 2.0 was listed as Amazon's top-selling non-fiction book of all time. Tom's other bestsellers include Strengths Based Leadership, Wellbeing, Eat Move Sleep, and Are You Fully Charged?Tom is currently co-founder and CEO of CareerSight. He previously led Gallup's workplaces business and served as a Senior Scientist. Tom was also a Vice-Chair of the VHL cancer research organization. He is a graduate of the University of Michigan and the University of Pennsylvania, where he has also been a guest lecturer.About Lainie:Lainie Rowell is a bestselling author, award-winning educator, and TEDx speaker. She is dedicated to human flourishing, focusing on community building, emotional intelligence, and honoring what makes each of us unique and dynamic through learner-driven design. She earned her degree in psychology and went on to earn both a post-graduate credential and a master's degree in education. An international keynote speaker, Lainie has presented in 41 states as well as in dozens of countries across 4 continents. As a consultant, Lainie's client list ranges from Fortune 100 companies like Apple and Google to school districts and independent schools. Learn more at ⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/lainierowell⁠⁠⁠⁠⁠⁠⁠⁠⁠.Website - ⁠LainieRowell.com⁠Instagram - ⁠⁠⁠⁠⁠⁠⁠⁠@LainieRowell⁠⁠⁠⁠⁠⁠⁠⁠LinkedIn - @LainieRowellX/Twitter - ⁠⁠⁠⁠⁠⁠⁠⁠@LainieRowell ⁠⁠⁠⁠⁠⁠⁠⁠Evolving with Gratitude, the book is available ⁠⁠⁠⁠⁠here!⁠⁠⁠⁠⁠⁠⁠ And now, Bold Gratitude: The Journal Designed for You and by You is available too!Both Evolving with Gratitude & Bold Gratitude have generous bulk pricing for purchasing 10+ copies delivered to the same location.

Send a textIn this deeply moving episode of unLimited with Elisabeth Carson, Elisabeth sits down with Lina El Zein to share a story of resilience, faith, and unimaginable strength.What started as mysterious symptoms and unexplained panic attacks eventually revealed something far more serious — a rare genetic condition called VHL that affects Lina and her children. For years, she was told her symptoms were psychological. The truth was something entirely different.In this raw and honest conversation, Lina opens up about:• Discovering the diagnosis that changed her life• The moment she learned she passed the condition to her children• Living year to year while holding on to hope• The emotional and spiritual strength it takes to keep showing up every day• Why science, faith, and community give her hope for the futureThis episode is not just about hardship — it's about perspective, courage, and the power of hope even in life's most uncertain moments.Lina's story is a powerful reminder that sometimes our greatest challenges reshape who we become.✨ Watch until the end for a perspective on life that will truly shift the way you see everything.⸻Follow Lina El Zein:Instagram: https://www.instagram.com/linaelzein⸻Listen to more episodes of unLimited with Elisabeth Carson:YouTube: https://youtube.com/@elisabethcarson⸻If you enjoy powerful conversations about healing, resilience, spirituality, and transformation, make sure to subscribe and turn on notifications so you never miss an episode. Support the show

In October 2023, Hoppe Hour And The Talk Yo Ishh!! Podcast collaborated for an hour of debauchery with the very beautiful Only Fans star known as Anna Blake. Listener Discretion Is Advised.

Dr. Pedro Barata and Dr. Rana McKay discuss the integration of innovative advances in molecular imaging and therapeutics to personalize treatment for patients with renal cell and urothelial carcinomas. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata, your guest host of By the Book, a podcast series featuring insightful conversations between authors and editors of the ASCO Educational Book. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. Now, we all know the field of genitourinary cancers (GU) is evolving quite rapidly, and we have new innovations in molecular imaging as well as targeted therapeutics. Today's episode will be exploring novel approaches that are transforming the management of renal cell and urothelial carcinomas and also their potential to offer a more personalized treatment to patients. For that, joining for today's discussion is Dr. Rana McKay, a GU medical oncologist and professor at University of California San Diego. Dr. McKay will discuss her recently published article titled, “Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas.”  Our full disclosures are available in the transcript of this episode.  And with that, Rana McKay, great to have you on the podcast today. Dr. Rana McKay: Oh, thank you so much, Dr. Barata. It's really wonderful to be here with you. So, thanks for hosting. Dr. Pedro Barata: No, thanks for taking the time, and I'm looking forward to this conversation. And by the way, let me start by saying congrats on a great article in the Educational Book. Really super helpful paper. I'm recommending it to a lot of the residents and fellows at my own institution. I would like to first ask you to kind of give our listeners some context of how novel approaches in the molecular imaging as well as targeted therapeutics are actually changing the way we're managing patients with GU, but specifically with renal cell carcinoma and urothelial carcinoma. So, what are the areas you would call out as like being big areas for innovation in this context, and why are they important? Dr. Rana McKay: Very good question. And I think this is really what this article highlights. It highlights where are we going from an imaging diagnostics standpoint? Where are we going from a therapeutic standpoint? And I think if we have to step back, from the standpoint of diagnostics, we've seen PET imaging really transform diagnostics in prostate cancer with the advent of PSMA PET imaging, and now PSMA PET imaging is used as a biomarker for selection for theranostics therapy. And so, we're starting to see that enter into the RCC landscape, enter into the urothelial cancer landscape to a lesser extent. And I think it's going to potentially be transformative as these tools get more refined. I think when we think about therapeutics, what's been transformative most recently in the renal cell carcinoma landscape has been the advent of HIF2α inhibition to improve outcomes for patients. And we have seen the approval of belzutifan most recently that has reshaped the landscape. And now there's other HIF2α inhibitors that are being developed that are going to be further important as they get refined. And lastly, I think when we think about urothelial carcinoma, the greatest transformation to treatment in that context has been the displacement of cisplatin and platinum-based chemotherapy as a frontline standard with the combination of enfortumab vedotin plus pembrolizumab. And we've seen antibody-drug conjugates really reshape treatment and tremendously improve outcomes for patients. So, I think those are the three key areas of interest. Dr. Pedro Barata: So with that, let's focus first on the imaging and then we'll get to the therapeutic area. So, we know there's been a paradigm shift, really, when prostate-specific targets emerged as tracers for PET scanning. And so, we now commonly use prostate-specific membrane antigen, or PSMA-based PET scanning, and really transform how we manage prostate cancer. Now, it appears that we're kind of seeing a similar wave in renal cell carcinoma with the new radiotracer against the target carbonic anhydrase IX. What can you tell us about this? And is this going to be available to us anytime soon? And how do you think that might potentially change the way we're managing patients with RCC today? Dr. Rana McKay: First, I'll step back and say that in the context of PSMA PET imaging, we have actually been able to better understand RCC as well. So, we know that PSMA is expressed in the neovasculature of tumors, and it can actually be used to detect renal cell carcinoma tumors. It has a detection rate of about 84% when used for detection. And so, you know, I don't think it's just restricted to carbonic anhydrase IX, but we will talk about that. So, PSMA expressed in the neovasculature has a detection rate of around 84%, particularly if we're looking at clear cell RCC. CAlX is overexpressed in clear cell RCC, and it's actually used in diagnosing renal cell carcinoma when we think of CAlX IHC for diagnosing clear cell RCC. And now there are CAlX PET tracers. The first foray was with the ZIRCON study that was actually an interestingly designed study because it was designed to detect the likelihood of PET imaging to identify clear cell RCC. So, it was actually used in the early diagnostics setting when somebody presents with a renal mass to discriminate that renal mass from a clear cell versus a non-clear cell, and it was a positive study. But when I think about the potential application for these agents, you know, I think about the entire landscape of renal cell carcinoma. This is a disease that we do treat with metastasis-directed therapy. We have certainly seen patients who've undergone metastasectomy have long, durable remissions from such an approach. And I think if we can detect very early onset oligometastatic disease where a metastasis-directed therapy or SABR could be introduced - obviously tested in a trial to demonstrate its efficacy - I think it could potentially be transformative. Dr. Pedro Barata: Wonderful. It's a great summary, and I should highlight you are involved in some of those ongoing studies testing the performance of this specific PET scanning for RCC against conventional imaging, right? And to remind the listeners, thus far, for the most part, we don't really do FDG-PET for RCC. There are some specific cases we do, but in general, they're not a standard scanning. But maybe that will change in the future. Maybe RCC will have their own PSMA-PET. And to your point, there's also emerging data about the role of PSMA-PET scanning in RCC as well, as you very elegantly summarized. Wonderful. So, let me shift gears a little bit because you did, in your introduction, you did highlight a novel MOA that we have in renal cell carcinoma, approved for use, initially for VHL disease, and after that for sporadic clear cell renal cell carcinoma. We're talking about hypoxia-inducible factor 2-alpha inhibitors, or HIF2α inhibitors, such as belzutifan. But there's also others coming up. So, as a way to kind of summarize that, what can you tell us about this breakthrough in terms of therapeutic class, this MOA that got to our toolbox of options for patients with advanced RCC? Tell us a little bit what is being utilized currently in the management of advanced RCC. And where do you see the future going, as far as, is it moving early on? Is it getting monotherapy versus combinations? Maybe other therapies? What are your thoughts about that? What can you tell us about it? Dr. Rana McKay: Belzutifan is a first-in-class HIF2α inhibitor that really established clinical validation for HIF2α as a therapeutic target. When we think about the activity of this agent, the pivotal LITESPARK-005 trial really led to the approval of belzutifan in patients who were really heavily pretreated. It was patients who had received prior IO therapy, patients who had received prior VEGF-targeted therapy. And in the context of this study, we saw a median PFS of 5.6 months, and there did seem to be a tail on the curve when you looked at the 12-month PFS rate with belzutifan. It was 33.7% compared to 17.6% with everolimus. And then when we look at the response rate, it was higher with belzutifan on the order of 22-23%, and very low with everolimus, as we've previously seen. I think one of the Achilles heels of this regimen is the primary PD rate, which was 34% when used in later line. There are multiple studies that are testing belzutifan in combination across the treatment landscape. So, we have LITESPARK-011, which is looking at the combination of belzutifan plus lenvatinib in the second-line setting. We've got the MK-012 [LITESPARK-012] study, which is looking at belzutifan in various combinations in the frontline setting. So there is a combination with IO plus belzutifan. And so this is also being looked at in that context. And then we also have the LITESPARK-022 study, which is looking at pembrolizumab with belzutifan in the adjuvant setting. So there's a series of studies that will be exploring belzutifan really across the treatment landscape. Many of these studies in combination. Additionally, there are other HIF2α inhibitors that are being developed. We have casdatifan, which is another very potent HIF2α inhibitor. You know, I think pharmacologically, these are different agents. There's a different half-life, different dosing. What is going to be the recommended phase 3 dose for both agents, the EPO suppression levels, the degree of EPO suppression, and sustainability of EPO suppression is very different. So, I think we've seen data from casdatifan from the ARC-20 trial from monotherapy with a respectable response rate, over 30%, primary PD rate hovering just around 10%.  And then we've also seen data of the combination of casdatifan with cabozantinib as well that were recently presented this year. And that agent is also being tested across the spectrum of RCC. It's being looked at in combination with cabozantinib in the PEAK-1 study, and actually just at the KCRS (Kidney Cancer Research Summit), we saw the unveiling of the eVOLVE-RCC trial, which is going to be looking at a volrustomig, which is a PD-1/CTLA-4 inhibitor plus casdatifan compared to nivo-ipi in the frontline setting.  So, we're going to see some competition in this space of the HIF2α inhibitors. I think when we think of mechanism of action in that these are very potent, not a lot of off-target activity, and they target a driver mutation in the disease. And that driver mutation happens very early in the pathogenesis. These are going to be positioned much earlier in the treatment landscape. Dr. Pedro Barata: All these studies, as you're saying, look really promising. And when we talk about them, you mentioned a lot of combinations. And to me, when I think of these agents, it makes a lot of sense to combine because there's not a lot of overlapping toxicities, if you will. But perhaps for some of our listeners, who have not used HIF2α inhibitors in practice yet, and they might be thinking about that, what can you tell us about the safety profile? How do you present it to your patients, and how do you handle things like hypoxia or anemia? How do you walk through the safety profile and tolerability profile of those agents like belzutifan? Dr. Rana McKay: I think these drugs are very different than your traditional TKIs, and they don't cause the classic symptoms that are associated with traditional TKIs that many of us are very familiar with like the rash, hand-foot syndrome, hypertension, diarrhea. And honestly, these are very nuanced symptoms that patients really struggle with the chronicity of being on a chronic daily TKI. The three key side effects that I warn patients about with HIF2α inhibitors are: (1) fatigue; (2) anemia; and (3) hypoxia and dysregulation in the ability to sense oxygen levels. And so, many of these side effects - actually, all of them - are very dose-dependent. They can be very well-managed. So, we can start off with the anemia. I think it's critically important before you even start somebody on belzutifan that you are optimizing their hemoglobin and bone marrow function. Make sure they don't have an underlying iron deficiency anemia. Make sure they don't have B12 or folate deficiency. Check for these parameters. Many patients who have kidney cancer may have some hematuria, other things where there could be some low-level blood loss. So, make sure that those are resolved or you're at least addressing them and supplementing people appropriately. I monitor anemia very closely every 3 to 4 weeks, at least, when people start on these medications. And I do initiate EPO, erythropoietin, should the anemia start to worsen. And I typically use a threshold of around 10g/dL  for implementing utilization of an EPO agent, and that's been done very safely in the context of the early studies and phase 3 studies as well. Now, with regards to the hypoxia, I think it's also important to make sure that you're selecting the appropriate individual for this treatment. People who have underlying COPD, or even those individuals who have just a very high burden of disease in their lung, lymphangitic spread, pleural effusions, maybe they're already on oxygen - that's not an ideal candidate for belzutifan. Something that very easily can be done in the clinic before you think about initiating somebody on this treatment, and has certainly been integrated into some of the trials, is just a 6-minute walk test. You know, have the patient walk around the clinic with one of the MAs, one of the nurses, put the O2 sat on [measuring oxygen saturation], make sure they're doing okay. But these side effects, like I said, are very dose-dependent. Typically, if a patient requires, if the symptoms are severe, the therapy can be discontinued and dose reduced. The standing dose is 120 mg daily, and there's two dose reductions to 80 mg and 40 mg should somebody warrant that dose modification. Dr. Pedro Barata: This is relatively new, right? Like, it was not that we're used to checking oxygen levels, right? In general, we're treating these patients, so I certainly think there's a learning curve there, and some of the points that you highlight are truly critical. And I do share many of those as well in our practice. Since I have you, I want to make sure we touch base on antibody-drug conjugates as well. It's also been a hot area, a lot of developments there. When I think of urothelial carcinoma and renal cell carcinoma, I see it a little bit different. I think perhaps in urothelial carcinoma, antibody-drug conjugates, or ADCs, are somewhat established already. You already mentioned enfortumab vedotin. I might ask you to expand a little bit on that. And then in renal cell carcinoma, we have some ADCs as well that you include in your chapter, and that I would like you to tell us what's coming from that perspective. So, tell us a little bit about how do you see ADCs in general for GU tumors, particularly UC and RCC? Tell us a little bit about the complexity or perhaps the challenges you still see. At the same time, tell us about the successes. Dr. Rana McKay: Stepping back, let's just talk about like the principles and design of ADCs. So, most ADCs have three components. There's a monoclonal antibody that typically targets a cell surface antigen, which is conjugated by a linker, which is the second component, to a payload drug. And typically, that payload drug has been chemotherapy, whether it be topoisomerase or whether it be MMAE or other chemotherapeutic. We can start in the RCC space. There's been multiple antibody-drug conjugates that have been tested. There's antibody-drug conjugates to CD70, which is expressed on clear cell RCC. There's been antibody-drug conjugates to ENPP3, which is also expressed on RCC. There's antibody-drug conjugates to CDH6. And they have different payloads, like I said, whether it be topoisomerase I or other microtubule inhibitors. Now, when we think about kidney cancer, we don't treat this disease with chemotherapy. This disease is treated with immunotherapy. It is treated with treatments that target the VEGF pathway and historically has not been sensitive to chemo. So, I think even though the targets have been very exciting, we've seen very underwhelming data regarding activity, and in some context, seen increased toxicity with the ADCs. So, I think we need to tread lightly in the context of the integration and the testing of ADCs in RCC. We just came back from the KCRS meeting, and there was some very intriguing data about a c-Kit ADC that's being developed for chromophobe RCC, which is, you know, a huge unmet need, these variant tumors that really lack appropriate therapeutics. But I just caution us to tread lightly around how can we optimize the payload to make sure that the tumor that we're treating is actually sensitive to the agent that's targeting the cell kill. So, that's a little bit on the ADCs in RCC. I still think we have a long way to go and still in early testing. Now, ADCs for UC are now the standard of care. I think the prototypical agent, enfortumab vedotin, is a nectin-4-directed ADC that's conjugated to an MMAE payload and was the first ADC approved for advanced urothelial, received accelerated approval following the EV-201 trial, which was basically a multicenter, single-arm study that was investigating EV in cisplatin-ineligible patients with advanced urothelial carcinoma, and then ultimately confirmed in the EV-301 study as well. And so, that study ended up demonstrating the support superiority of EV from an overall survival standpoint, even PFS standpoint. Building on that backbone is the EV-302 study, which tested EV in combination with pembrolizumab versus platinum-based chemotherapy in the frontline setting. And that was a pivotal, landmark study that, like I said, has displaced platinum therapy as a frontline treatment for people with advanced urothelial carcinoma. And when we think about that study and the median overall survival and just how far we've come in urothelial cancer, the median OS with EV-pembro from that trial was 31 and a half months. I mean, that's just incredible. The control arm survival was 16 and a half months. The hazard ratio for OS, 0.47. I mean this is why when this data was presented, it was literally a standing ovation that lasted for several minutes because we just haven't seen data that have looked that good. And there are other antibody-drug conjugates that are being tested. We've all been involved in the saga with sacituzumab govitecan, which is a trophoblast cell surface antigen 2 (Trop-2) targeted ADC with a topoisomerase I payload. It was the second ADC to receive approval, but then that approval was subsequently withdrawn when the confirmatory phase 3 was negative, the TROPiCS-04 trial. So, approval was granted based off of the TROPHY-U-01, single-arm, phase 2 study, demonstrating a response rate of around 28% and a PFS of, you know, about 5 and a half months. But then failure to show any benefit from an OS standpoint. And I think there's a lot of controversy in the field around whether this agent still has a role in advanced urothelial carcinoma. And I think particularly for individuals who do not have molecular targets, like they're not HER2-amplified or have HER2-positivity or FGFR or other things like that. Dr. Pedro Barata: Fantastic summary, Rana. You were talking about the EV, and it came to mind that it might not be over, right, for the number of ADCs we use in clinical practice in the near future. I mean, we've seen very promising data for ADC against the HER2, right, and over-expression. It also can create some challenges, right, in the clinics because we're asking to test for HER2 expression. It's almost like, it's not exactly the same to do it in breast cancer, but it looks one more time that we're a little bit behind the breast cancer field in a lot of angles. And also has vedotin as a payload. Of course, I'm referring to disitamab vedotin, and there's very elegant data described by you in your review chapter as well. And it's going to be very interesting to see how we sequence the different ADCs, to your point as well. So, before we wrap it up, I just want to give you the opportunity to tell us if there's any area that we have not touched, any take-home points you'd like to bring up for our listeners before we call it a day. Dr. Rana McKay: Thank you so much. I have to say, you know, I was so excited at ASCO this year looking at the GU program. It was fantastic to see the progress being made, novel therapeutics that really there's a tremendous excitement about, not just in RCC and in UC, but also in prostate cancer, thinking about the integration of therapies, not just for people with refractory disease that, even though our goal is to improve survival, our likelihood of cure is low, but also thinking about how do we integrate these therapies early in the treatment landscape to enhance cure rates for patients, which is just really spectacular. We're seeing many of these agents move into the perioperative setting or in combination with radiation for localized disease. And then the special symposium on biomarkers, I mean, we've really come a long, long way. And I think that we're going to continue to evolve over the next several years. I'm super excited about where the field is going in the treatment of genitourinary malignancies. Dr. Pedro Barata: Oh, absolutely true. And I would say within the Annual Meeting, we have outstanding Educational Sessions. And just a reminder to the listeners that actually that's where the different teams or topics for the Educational Book chapters come from, from actually the educational sessions from ASCO. And your fantastic chapter is an example of that, right, focusing on advanced GU tumors. So, thank you so much, Rana, for taking the time, sharing your insights with us today on the podcast. It was a fantastic conversation as always. Dr. Rana McKay: My pleasure. Thanks so much for having me, Dr. Barata. Dr. Pedro Barata: Of course.  And thank you to our listeners for your time today. You will find the link to the article discussed today in the transcript of this episode. I also encourage you to check out the 2025 ASCO Educational Book. You'll find an incredible wealth of information there. It's free, available online, and you'll find, hopefully, super, super important information on the key science and issues that are shaping modern oncology, as we've heard from Dr. McKay and many other outstanding authors. So, thank you, everyone, and I hope to see you soon. 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. Follow today's speakers:        Dr. Pedro Barata @PBarataMD Dr. Rana McKay @DrRanaMcKay Follow ASCO on social media:        @ASCO on X (formerly Twitter)        ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck  Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion, Calithera, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Esiai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol Myers Squibb, Merck, Astrazeneca, Myovant Research Funding (Inst.): Bayer, Tempus, AstraZeneca, Exelixis, Bristol Myers Squibb, Oncternal Therapeutics, Artera    

Après 870 matchs dans la LNH et une coupe Stanley remportée avec le Lightning en 2021, David Savard a tiré sa révérence du hockey professionnel le 30 avril dernier, à la suite de l'élimination des Canadiens en séries éliminatoires. Le vétéran défenseur aborde sa crainte d'être échangé lors de la dernière période des transactions, sa déception de ne pas avoir remporté la coupe à Montréal, son souhait de rester dans l'organisation du CH et son respect pour Martin St-Louis. Écoutez le nouveau retraité faire le point sur sa carrière et aborder l'avenir des Canadiens avec Mario Langlois. Sebastian Aho est-il l'un des joueurs élites les plus sous-estimés de la LNH? Martin McGuire analyse le jeu de l’attaquant des Hurricanes, qui n’a pas froid aux yeux face à Tom Wilson des Capitals. Autrement, le descripteur des Canadiens au Réseau Cogeco aborde l’utilité d'Evander Kane chez les Oilers . Selon lui, il change l'identité de l'équipe! Louis Robitaille quitte son poste d'entraîneur chez les Eagles du Cap-Breton de la LHJMQ pour relever un nouveau défi en Russie avec l'organisation de Omskie Krylia, le club-école de la VHL de l’Avangard d’Omsk, dirigée par Guy Boucher, dans la KHL. Pourquoi quitter la LHJMQ pour la VHL? Écoutez Louis Robitaille répondre à la question au micro de Mario Langlois. Le Rocket de Laval affrontera les Americans de Rochester mercredi au prochain tour des séries éliminatoires dans la Ligue américaine de hockey. Écoutez Stéphane Leroux faire le point sur les aspects à surveiller du côté du Rocket. Le spécialiste du hockey junior à RDS analyse également la finale de la LHJMQ entre les Wildcats et l'Océanic. Cette dernière se transporte à Rimouski pour les matchs 3 et 4. Leroux avoue être impressionné par le niveau de jeu relevé. Selon ses dires, 13 des 28 joueurs de la LHJMQ actuellement repêchés par une équipe de la LNH jouent pour Rimouski et pour Moncton. Voir https://www.cogecomedia.com/vie-privee pour notre politique de vie privée

This Week's Show: Canadiens Display Playoff Grit, Heart, Resilience Against Capitals Segment 1 | Week in Review, Habs News, League News⦁ Injury issues for Patrik Laine, Sam Montembeault and Logan Thompson.⦁ Canadiens prospect sets VHL playoff record.⦁ Laval Rocket and Trois-Rivières Lions await next playoff opponent.Segment 2 | How the Canadiens Are Earning Respect This Playoff Series Things are not how you might think. Here are the real reasons that the Montreal Canadiens are earning the respect of the Washington Capitals in their first round playoff series.Segment 3 | Have Your SayCanadiens upcoming events.Canadiens Connection question of the week: Which player has shown the most heart and character during this series in your eyes?Listener's texts and emails.Get the Canadiens Connection!Use our single link here to subscribe to the Canadiens Connection your favorite podcast app.Be sure to follow @habsconnection on Twitter, Facebook, InstagramA new episode of the Canadiens Connection podcast is available weekly on Saturday afternoon. Missed an episode? You can download every episode of the Canadiens Connection HERE.Canadiens Connection on Rocket Sports RadioThank you for listening to the Canadiens Connection. This engaging podcast connects Habs fans with their beloved team from a plugged-in source they know and trust.Canadiens Connection is hosted by Rick Stephens (@RocketSports) with Amy Johnson (@FlyersRule). This talented team of credentialed journalists come together to share their valued insight.

Send us a textParis O'Brien shares his remarkable journey from quitting hockey at age 15 to becoming the Chinese national hockey goaltender and Olympian. His story demonstrates how stepping away from sport temporarily can sometimes be the catalyst for future success when combined with passion, hard work, and being ready when opportunity arises.• Growing up playing minor hockey in Coquitlam before deciding to take a year off at age 15-16• Returning to hockey with Delta Hockey Academy before being spotted by Mike Keenan at a tryout • Playing professionally in Finland at 17, then in Russia's VHL and KHL before the Olympics• The critical importance of mental training for goaltenders—"90% mental, 10% physical"• Working with mindset coach Pete Fry and now mentoring younger goalies himself• Using technology like Visual Edge and Sensorina to train cognitive aspects of goaltending• Comprehensive recovery protocols including cold tubs, heat therapy, and compression boots• Playing at the Olympics against Team Canada after briefly practicing with them• Custom gear setup including a helmet painted by his girlfriend artist• Balancing hockey with other interests to maintain mental health and perspectiveIf you enjoyed this episode, follow the Athletes Podcast on social media and let us know who you'd like to see featured next in the YouTube comments. Check out our Website | Twitter | LinkedIn | Instagram | Tiktok | Spotify | Apple | Google | Youtube l Save 20% on Perfect Sports Supplements

Link for CME Credit: https://uthscsa.edu/medicine/education/cme/pediatrics-now-podcast In this episode of Pediatrics Now, host Holly Wayment discusses Von Hippel-Lindau (VHL) Syndrome with leading experts Dr. Gail Tomlinson and Dr. Patricia Dahia from the University of Texas Health Science Center 's Department of Pediatrics and University Health.  This genetic disorder is characterized by the development of various tumors and cysts in different parts of the body, linked to mutations in the VHL gene. The conversation delves into the history and genetic mechanisms of VHL Syndrome, highlighting its rarity and complex nature. Dr. Tomlinson and Dr. Dahia provide insights into the symptoms, diagnosis, and the groundbreaking development of a new FDA-approved drug that offers hope for managing the disease's manifestations. Pediatric Practitioner Listeners will gain an understanding of how genetic research has transformed treatment options, moving towards precision medicine, and offering newfound hope for individuals with this challenging condition, and other conditions. Join us to explore the impact of precise genetic interventions and the ongoing research shaping the future of VHL Syndrome treatment. Additional sources for this episode include The New York Times and Wikipedia.

Hereditary Kidney Cancer Syndromes CME Available: https://auau.auanet.org/node/41772 ACKNOWLEDGEMENTS: Support provided by an independent educational grant from:  Merck & Co., Inc.  LEARNING OBJECTIVES: At the conclusion of this activity, participants should be able to: 1. Select patients who should undergo genetic testing to identify hereditary kidney cancer syndromes based on appropriate criteria, including family history and clinical presentation. 2. Implement strategies to address ethical concerns related to genetic testing, such as patient consent, confidentiality, and the potential impact on family members. 3. Discuss VHL syndrome, including its genetic basis, inheritance pattern, and associated tumors. 4. Properly diagnose and manage VHL syndrome in clinical practice based on knowledge of novel therapeutic strategies. 5. Utilize a multidisciplinary approach consisting of urologists, oncologists, geneticists and nephrologists when managing hereditary kidney cancer syndromes.

Drs. Mehdi Mollapour, Jennifer Heritz, and Sarah Backe from SUNY Upstate Medical University (Syracuse, NY) discuss a review they co-authored that was published by Oncotarget in Volume 15, entitled, “Molecular chaperones: Guardians of tumor suppressor stability and function.” DOI - https://doi.org/10.18632/oncotarget.28653 Correspondence to - Mehdi Mollapour - mollapom@upstate.edu Video interview - https://www.youtube.com/watch?v=vEHmyemWgNo Video transcript - https://www.oncotarget.net/2024/10/24/behind-the-study-molecular-chaperones-tumor-suppressor-stability/ Abstract The term ‘tumor suppressor' describes a widely diverse set of genes that are generally involved in the suppression of metastasis, but lead to tumorigenesis upon loss-of-function mutations. Despite the protein products of tumor suppressors exhibiting drastically different structures and functions, many share a common regulatory mechanism—they are molecular chaperone ‘clients'. Clients of molecular chaperones depend on an intracellular network of chaperones and co-chaperones to maintain stability. Mutations of tumor suppressors that disrupt proper chaperoning prevent the cell from maintaining sufficient protein levels for physiological function. This review discusses the role of the molecular chaperones Hsp70 and Hsp90 in maintaining the stability and functional integrity of tumor suppressors. The contribution of cochaperones prefoldin, HOP, Aha1, p23, FNIP1/2 and Tsc1 as well as the chaperonin TRiC to tumor suppressor stability is also discussed. Genes implicated in renal cell carcinoma development—VHL, TSC1/2, and FLCN—will be used as examples to explore this concept, as well as how pathogenic mutations of tumor suppressors cause disease by disrupting protein chaperoning, maturation, and function. Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28653 Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/ Keywords - cancer, molecular chaperone, tumor suppressor, renal cell carcinoma, Birt-Hogg-Dubé (BHD) syndrome, TSC syndrome About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Hereditary Kidney Cancer Syndromes CME Available: https://auau.auanet.org/node/41772 ACKNOWLEDGEMENTS: Support provided by an independent educational grant from:  Merck & Co., Inc.  LEARNING OBJECTIVES: At the conclusion of this activity, participants should be able to: 1. Select patients who should undergo genetic testing to identify hereditary kidney cancer syndromes based on appropriate criteria, including family history and clinical presentation. 2. Implement strategies to address ethical concerns related to genetic testing, such as patient consent, confidentiality, and the potential impact on family members. 3. Discuss VHL syndrome, including its genetic basis, inheritance pattern, and associated tumors. 4. Properly diagnose and manage VHL syndrome in clinical practice based on knowledge of novel therapeutic strategies. 5. Utilize a multidisciplinary approach consisting of urologists, oncologists, geneticists and nephrologists when managing hereditary kidney cancer syndromes.

Dr. Neeraj Agarwal and Dr. Rana McKay discuss promising studies in GU cancers featured at the 2024 ASCO Annual Meeting that highlighted improved outcomes in urothelial carcinoma, improved survival in renal cell carcinoma, and the role of ctDNA as a potential biomarker for predicting outcomes.   TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News.  I am delighted to welcome Dr. Rana McKay, a GU medical oncologist and associate professor at the University of California San Diego. Today, we'll be discussing some key GU abstracts featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Rana, we're thrilled to have you on the podcast today to share your insights on key advances in GU oncology from ASCO24. Dr. Rana McKay: Thank you so much, Neeraj; it's a pleasure to be here. Dr. Neeraj Agarwal: So, Rana, let's start with some bladder cancer abstracts. Could you tell us about Abstract 4503, titled “Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer”? Dr. Rana McKay: Of course, I would be delighted to. First, I would like to remind our listeners that enfortumab vedotin (EV) was approved as a monotherapy for the treatment of locally advanced or metastatic urothelial cancer based on the results of EV-201 and EV-301 trials. In these pivotal studies, EV was initiated at a dose of 1.25 mg/kg, and dose modifications, such as reductions and interruptions, were used to manage adverse events. In the abstract presented at ASCO 2024, Dr. Daniel Petrylak and colleagues conducted a post-hoc exploratory analysis to evaluate the association between EV plasma exposure and outcomes. They used multiple pharmacokinetic samples collected during the first two cycles and pre-dose samples from 3 EV monotherapy studies, namely EV-101, EV-201, and EV-301, that were conducted in patients with previously treated locally advanced or metastatic urothelial carcinoma. Dose reductions to 1 mg/kg were required in 42.1% and 35.1% of patients in the EV-201 and EV-301 trials, respectively, and reductions to 0.75 mg/kg were required in 13.6% and 11.1% in the EV-201 and EV-301 trials, respectively. Higher EV exposure during the first two cycles was associated with a higher objective response rate. The ORR was 21.4% for the dose of 0.75 mg/kg, while it was 18.5% for the dose of 1.0 mg/kg. Interestingly, increasing the dosage to 1.25 mg/kg improved the ORR, which ranged from 40 to 51.1% across various studies. In the EV-301 trial, when comparing the efficacy of EV to chemotherapy, EV improved PFS and OS across all dose quartiles, and there was no evidence that recommended dose modifications impacted long-term efficacy outcomes. Dr. Neeraj Agarwal: Thank you, Rana, for this great summary. I would like to add that the meticulously conducted pharmacokinetic studies demonstrated that serum levels of EV correlated with responses. Importantly, patients who had to decrease the dose did not experience compromised outcomes as EV improved PFS and OS outcomes vs chemotherapy in across all exposure quartiles in the EV-301 trial where EV was compared with chemotherapy. These findings highlight the need to start at the recommended dose of 1.25 mg/kg and reduce it, if necessary, however, clinicians should not start at a lower dose.  Dr. Rana McKay: I totally agree with you, Neeraj. Now, moving on to a different setting in bladder cancer, what can you tell us about LBA4517, titled “Perioperative sacituzumab govitecan alone or in combination with pembrolizumab for patients with muscle-invasive urothelial bladder cancer: SURE-01/02 interim results”? Dr. Neeraj Agarwal: Of course! So, SURE was a multicohort, open-label, phase 2 study in patients with muscle-invasive bladder cancer assessing sacituzumab govitecan as a neoadjuvant therapy either alone in SURE-01 or as a combination with pembrolizumab followed by adjuvant pembro in SURE-02 in a flexible design allowing a bladder-sparing approach. In the abstract presented at ASCO 2024, Dr. Antonio Cigliola and colleagues report interim results of the SURE-01 study. Patients with cT2-4N0M0 urothelial carcinoma who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy were planned to receive 4 cycles of neoadjuvant sacituzumab govitecan at a dose of 10 mg/kg followed by radical cystectomy.  An extensive assessment was performed at baseline and after the 4 cycles for response assessment. Patients with clinical complete response defined with negative MRI, cystoscopy and ctDNA assays refusing radical cystectomy were offered redo transurethral resection of the bladder tumor or repeat TURBT followed by observation in the absence of viable high-grade tumor in the bladder. The primary endpoint was pathological complete response rate, while secondary endpoints included pathological downstaging rate and safety. After the first 8 patients were enrolled, the protocol was amended due to the occurrence of grade 3 and 4 neutropenia and diarrhea in 75% and 50% of patients, respectively, and 2 deaths – one of which was deemed to be treatment-related due to sepsis. Key protocol changes included the reduction of the dose of sacituzumab govitecan to 7.5 mg/kg, the introduction of G-CSF as primary prophylaxis, and the exclusion of patients at high risk of febrile neutropenia per ASCO guidelines.  Among 21 patients who received at least one cycle of sacituzumab govitecan and included in the intention-to-treat population, 47.6% had a complete pathological response, and 52.4% had pathological downstaging. 11 patients underwent radical cystectomy, while 7 received repeat-TURBT due to complete clinical response or patient preference. Regarding the safety profile, grade 3 or more adverse events occurred in 42.5% of patients. Treatment-related adverse events leading to dose interruptions or discontinuations were more common before the protocol amendment. It is noteworthy that 3 patients died after treatment discontinuation, with one deemed treatment-related, as previously mentioned. Dr. Rana McKay: Thank you, Neeraj, for a great summary. The pathological complete responses observed show promising activity for sacituzumab govitecan as a neo-adjuvant therapy and a window for bladder-sparing approaches, which is definitely exciting news for our patients! However, although the 3 deaths encountered in a neo-adjuvant setting could be concerning, the improvement of the safety profile after protocol amendments is reassuring and supports the continuation of the study. Dr. Neeraj Agarwal: Before wrapping up the bladder cancer section, would you like to share your insights with our listeners on Abstract 4518, titled “Quantitative circulating tumor DNA (ctDNA) assessment in patients with advanced urothelial carcinoma treated with pembrolizumab or platinum-based chemotherapy from the phase 3 KEYNOTE-361 trial”?  Dr. Rana McKay: Sure. So, the KEYNOTE-361 trial was a randomized phase 3 study with 3 arms that included pembrolizumab plus chemotherapy, pembrolizumab monotherapy, or chemotherapy alone in patients with previously untreated advanced urothelial carcinoma. The results showed that neither the combination of pembrolizumab plus chemotherapy nor pembrolizumab monotherapy improved survival outcomes compared to the chemotherapy arm. So, in this exploratory analysis presented at ASCO24, Dr. Tom Powles and colleagues sought to assess the role of ctDNA as a potential biomarker between the pembrolizumab monotherapy arm and the chemotherapy arm. Tumor tissue mutations were evaluated using whole exome sequencing, and plasma ctDNA was assessed with the Guardant 360 assay. Changes in ctDNA from pre-treatment cycle 1 to on-treatment cycle 2, so 3 weeks post-baseline assessment, were quantified by the maximum variant allele frequency of tumor tissue-specific mutations.  Results showed that lower baseline ctDNA levels were associated with improved clinical outcomes of response in the pembrolizumab arm but not in the chemotherapy arm. This improvement in the pembrolizumab arm was also robust to adjustment for tumor mutational burden and PD-L1. Additionally, chemotherapy led to a ctDNA clearance rate of 41% compared to 11% in the pembrolizumab arm. Patients who had a large ctDNA reduction with pembrolizumab had significantly improved outcomes compared to those achieving a large reduction with chemotherapy with a hazard ratio of 0.25. However, this did not replicate in patients who did not achieve a large reduction, as these patients had similar outcomes across both arms. Let's switch gears to kidney cancer and start with Abstract 4508, reporting the final OS analysis from the JAVELIN Renal-101 trial. Neeraj, what would you like to tell us about this abstract? Dr. Neeraj Agarwal:  Well, as a quick reminder, the JAVELIN Renal-101 was a randomized phase 3 trial where patients with previously untreated advanced or metastatic clear cell renal cell carcinoma were randomized to receive either the combination of avelumab plus axitinib or sunitinib. In previous analyses, the combination of avelumab and axitinib significantly improved PFS compared to sunitinib and was subsequently approved by the FDA for the first-line treatment of patients with advanced RCC in 2019. This superiority in PFS was maintained across the different analyses; however, OS data remained immature. In the abstract presented at ASCO24 by Dr. Robert Motzer from Memorial Sloan Kettering Cancer Center and colleagues, the authors reported OS results at a median follow-up of around 73 months and a minimum of 68 months for all patients, which is the longest follow-up for any ICI-TKI combination in RCC. The final analysis in the overall population favored the combination of avelumab plus axitinib with a median OS of 44.8 months compared to 38.9 months with sunitinib, however, this did not reach statistical significance with a hazard ratio of 0.88. The PFS results and safety profile were consistent with previous analyses.  Dr. Rana McKay: Thank you, Neeraj, for such a nice overview of this abstract. These new data could make this regimen less optimal than other ICI-TKI combinations in the first-line mRCC setting.   Dr. Neeraj Agarwal: I concur, Rana. Moving on to perhaps one of the most exciting GU abstracts featured, Abstract 4506, titled “Circulating kidney injury molecule-1 biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection.” Rana, what are your thoughts on this abstract? Dr. Rana McKay: Well, first, I would like to take a step back and remind our audience that in the IMmotion010 trial, patients with resected intermediate to high-risk RCC with clear cell and/or sarcomatoid component were randomized in a 1:1 ratio to receive either atezolizumab or placebo. Investigator-assessed disease-free survival, which was the primary endpoint, favored the atezolizumab arm but did not reach statistical significance. In the abstract featured at ASCO24, Dr. Laurence Albiges and colleagues build on data previously reported in the ASSURE and CheckMate 914 trials and report provocative findings regarding a molecule known as kidney injury molecule 1 or KIM-1, which is a type 1 membrane glycoprotein that has been identified as a minimally invasive potential peripheral blood circulating biomarker. The KIM-1 level of 86 pg/ml was identified as the optimized threshold for defining post-nephrectomy KIM-1 high vs KIM-1 low subgroups in the IMmotion010 trial. KIM-1 levels were measured at baseline or pre-treatment, at cycle 4 day 1, and at disease recurrence or discontinuation without disease recurrence. Baseline characteristics were balanced between the KIM-1 high and KIM-1 low groups, except perhaps for a slightly higher pathological stage in the KIM-1 high subgroup.  I would like to highlight 3 key takeaways from this abstract. First, KIM-1 high level was associated with significantly worse DFS with a hazard ratio of 1.75. Second, patients in the KIM-1 high subgroup receiving atezolizumab had a 28% reduction in the risk of recurrence or death compared to those receiving placebo, while those in the KIM-1 low subgroup had comparable outcomes across both treatment arms. Third, patients in the KIM-1 high subgroup receiving atezolizumab were significantly less likely to experience an on-treatment increase in KIM-1 levels, which was associated with worse DFS in both high and low KIM-1 subgroups, regardless of treatment arm. Thus, these findings support the use of KIM-1 as both a predictive and prognostic biomarker in patients with RCC. Dr. Neeraj Agarwal: Yes, Rana, this is amazing data! I would like to add that these results warrant larger and, ideally, prospective studies to validate the utility of KIM-1 as a noninvasive biomarker for identifying minimal residual disease after nephrectomy and for predicting outcomes to immune checkpoint inhibitors. Dr. Rana McKay: Also, in the field of biomarkers, 2 abstracts interrogating different biomarkers in a different setting, so in patients with advanced or metastatic RCC were presented. Neeraj, could you tell us more about these abstracts? Dr. Neeraj Agarwal: Of course! I think you are referring to Abstracts 4504 and 4505. In abstract 4504, Dr. Toni Choueiri and colleagues sought to assess the clinical implications of different biomarkers in the CLEAR trial, which was a randomized phase 3 trial that led to the approval of the combination of pembrolizumab plus lenvatinib in the first-line mRCC setting. On the other hand, in abstract 4505, Dr. Brian Rini presented biomarker results in KEYNOTE-426, which was also a randomized phase 3 trial based on which the combination of pembrolizumab plus axitinib was approved in patients with mRCC. The authors in both trials sought to investigate the role of biomarkers in predicting treatment outcomes from 3 different angles. Starting with PD-L1 expression, the superiority of the combination arms over sunitinib was not impacted by PD-L1 status in both trials. Moving on to RCC driver gene mutations on whole exome sequencing, such as VHL, SETD2, PBRM1, and BAP1, ICI combination therapies improved outcomes regardless of mutation gene status, and this improvement was statistically significant with PBRM1 mutations in KEYNOTE-426 compared to wild-type PBRM1, but this did not replicate in the CLEAR trial. Finally, using transcriptomic signatures derived from RCC trials, especially the IMmotion 151 and JAVELIN Renal 101 trials, where 7 clusters or molecular subtypes were identified, the combination arms outperformed sunitinib in all clusters in both trials and the magnitude of this benefit differed across clusters.  Dr. Rana McKay: Thank you for this very interesting summary and comparison of the results of these 2 abstracts. These findings support the use of ICI-based combinations in all patients with mRCC as a first-line option. Although these abstracts could not identify specific biomarkers that could guide us clinicians in treatment selection, they provide very interesting biological insights on these molecular biomarkers that are, however, not yet clinically actionable. Dr. Neeraj Agarwal: Very interesting point, Rana. Moving on to prostate cancer, let's start with abstract LBA5000 titled, “Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: The CHAARTED2 trial of the ECOG-ACRIN Cancer Research Group (EA8153).” Rana, what is your takeaway on this abstract? Dr. Rana McKay: As a reminder to our audience, the CHAARTED2 trial was a randomized open-label phase 2 study that compared the combination of cabazitaxel and abiraterone to abiraterone alone in patients with mCRPC previously treated with ADT plus docetaxel in the hormone-sensitive setting. The primary endpoint was progression-free survival. After a median follow-up of 47.3 months, Dr. Christos Kyriakopoulos and colleagues reported in LBA5000 that patients receiving the combination of cabazitaxel plus abiraterone had a 27% reduction in the risk of progression or death. However, there was no significant difference in overall survival between the two arms, with a median OS of 25 months in the cabazitaxel+abiraterone arm and 26.9 months in the abiraterone arm, although the study was underpowered for this endpoint. Regarding the toxicity profile, the combination of cabazitaxel and abiraterone was overall well tolerated with more cytopenias, as expected.  Dr. Neeraj Agarwal: Very nice summary of this abstract, Rana. I would like to add that the treatment landscape of patients with mHSPC has evolved since the design of the study and now includes combination therapies of ADT + ARPI with or without docetaxel, and ADT + docetaxel is no longer a standard of care, which limits the applicability of these results in clinical practice today.  Dr. Rana McKay: Excellent point, Neeraj. Let's discuss Abstract 5001, titled “CYCLONE 2: A phase 3 study of abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer”. Dr. Neeraj Agarwal: Sure! In the abstract featured at ASCO24, Dr. Matthew Smith and colleagues report the primary results of the CYCLONE 2 trial, which was a randomized phase 2/3 study that investigated the combination of abemaciclib plus abiraterone versus abiraterone monotherapy in patients with mCRPC. Stratification factors included radiographic progression at study entry, presence of measurable disease, and prior docetaxel for mHSPC. Part 1 of the study established the recommended phase 2 dose of abemaciclib at 200 mg twice daily. In part 2, patients were randomized to placebo or abemaciclib, and an adaptive interim analysis using prespecified criteria was performed and recommended the expansion of the study to part 3. The primary endpoint was investigator-assessed radiographic progression-free survival by RECIST 1.1 and PCWG3 criteria in the intention-to-treat population. At the time of the primary analysis, adding abemaciclib to abiraterone did not improve rPFS, with a hazard ratio of 0.83. The median rPFS was 22 months for the combination arm and 20.3 months for the abiraterone arm. The combination was well tolerated, and the safety profile was consistent with the known adverse events. Dr. Rana McKay: So, the addition of abemaciclib to abiraterone did not improve outcomes in patients with mCRPC. These findings suggest that no further investigation is warranted for abemaciclib or CDK4/6 inhibitors in biomarker-unselected patients with prostate cancer.  Dr. Neeraj Agarwal: Rana, what's your take-home message on Abstract 5006, titled “Health-related quality of life results from PRESTO (AFT-19), a phase 3 randomized trial of intensification of androgen blockade in patients with high-risk biochemically relapsed castration sensitive prostate cancer”? Dr. Rana McKay: So, as a reminder to our audience, the PRESTO trial was a randomized phase 3 study that assessed the effects of intensified androgen receptor blockade in patients with biochemically recurrent prostate cancer following local therapies. Patients with a PSA doubling time of less than 9 months and no evidence of metastatic disease were randomized to receive either 52 weeks of ADT alone, ADT plus apalutamide, or ADT plus apalutamide plus abiraterone. In their paper published earlier this year in the Journal of Clinical Oncology, the authors showed that patients receiving ADT plus apalutamide with or without abiraterone had significantly longer PSA-progression-free survival than those receiving ADT alone. In the oral presentation featured at ASCO24, Dr. Ronald Chen and colleagues report health-related quality of life outcomes that were assessed using various questionnaires or scales at baseline, at cycle 7, which is around 6 months on treatment, and at the end of treatment. Results showed that this intensified approach with apalutamide did not significantly increase severe adverse events, did not lengthen the time to testosterone recovery, and did not meaningfully increase common treatment-related symptoms such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue. Importantly, additional intensification with abiraterone did not further improve PSA-PFS but did increase the rate of serious adverse events, lengthened the time to testosterone recovery, and increased hot flash interference.  Dr. Neeraj Agarwal: So, in conclusion, the PRESTO trial supports using intensified androgen blockade with apalutamide to improve PSA-PFS in patients with high-risk biochemically recurrent prostate cancer without compromising health-related quality of life. However, adding abiraterone did not offer additional benefits and increased side effects.  Dr. Rana McKay: Let's move on to LBA5002 titled, “A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.” Would you like to share your insights on this abstract with our listeners? Dr. Neeraj Agarwal: Absolutely. MAST was a randomized, double-blinded, placebo-controlled trial that investigated the impact of metformin on the progression of low-risk localized prostate cancer in patients choosing to undergo active surveillance. Eligible patients had biopsy-proven, low-risk, localized prostate cancer diagnosed within the past 6 months, characterized by a Gleason score of less than 6 observed in less than one-third of the total cores, less than 50% positivity in any one core, a PSA level of less than 10 ng/ml, and a clinical-stage between T1c and T2a. Patients were randomized in a 1:1 ratio to receive either metformin 850 mg twice daily or placebo for three years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint was time to progression, defined as the earliest occurrence of primary prostate cancer therapy, such as prostatectomy, radiation, hormonal therapy, or pathological progression on subsequent biopsies, which was defined as more than 1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher. The study included 407 patients, with 204 receiving metformin and 203 receiving a placebo. Results presented by Dr. Anthony Joshua showed no statistically significant difference in progression-free survival, including therapeutic and pathologic progression, with an unadjusted hazard ratio of 1.08.  Interestingly, there was a signal that patients with a BMI more than 30 had a detriment to taking metformin with a higher risk of progression compared to those receiving placebo with an unadjusted HR of 2.39 and a p-value of 0.01. Dr. Rana McKay: I would like to add that this study showed that metformin use does not prevent the progression of low-risk localized prostate cancer on active surveillance and could represent a potential detriment for patients with high BMI at study entry. Dr. Neeraj Agarwal: Yes, Rana, I concur. Any final remarks before we conclude today's podcast? Dr. Rana McKay:  Thank you, Neeraj; it's been wonderful being here with you today and you having me on the podcast to highlight these important advances and the amazing work that many investigators are conducting and the patients who were involved in the context of these trials. It's really excellent to see these updated results.   Dr. Neeraj Agarwal: Before we wrap up this podcast, I would like to say that we have reviewed a selection of abstracts addressing prostate, bladder, and kidney cancer, which are significantly impacting our medical practices now and in the near future. Rana, thank you for sharing your insights today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion. Many thanks. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, 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.   Find out more about today's speakers:    Dr. Neeraj Agarwal   @neerajaiims   Dr. Rana McKay  @DrRanaMcKay     Follow ASCO on social media:      @ASCO on Twitter      ASCO on Facebook      ASCO on LinkedIn         Disclosures:        Dr. Neeraj Agarwal:         Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences     Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas      Dr. Rana McKay:   Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus

On this episode of Raising Rare we talk with Stacy Lloyd, a rare disease patient and board certified patient advocate. Stacy has dedicated her life, even much of her free time to healthcare in one way or another. She currently works at the American Medical Association, previously at Saavy Co-op, and is on the board of the VHL Alliance. After being diagnosed with Von Hippel-Lindau (VHL) at a young age, doctors told Stacy that she might not be able to walk as she got older and tumors continued to grow. She went on believing this for most of her early adult life and even admits that she never thought about retirement or other aspects of growing older because they just wouldn't pertain to her. It wasn't until 2018 that a doctor she met at a medical conference for VHL told her that she was going to be alright, she would be just fine, that she started to really consider her life.Stacy's diagnosis of having a rare genetic condition at an early age actually led to a number of her family members being diagnosed as well. Stacy speaks with us candidly that not everyone has handled their diagnosis with as much hope and drive as she has and that a number of factors have played into that. Stacy's hope for members of the rare community is that everyone continues to share their stories, that they continue being vulnerable with each other and their medical team because you never know who will benefit from you doing so.Mentioned in this episode:Invitation to Check Out The AtlasThe Atlas

Subscribe to MamamiaOn September 10, 2023,  17-year-old Fletcher Crowley's life changed in an instant when an ordinary day out with his mates went bad. In that moment, his whole family was impacted in ways they're only just starting to understand. So six months later, how are they doing? Fletcher and his parents, Nicky and Pat join Mia Freedman to talk about that day and the unexpected aftermath.You can help the Crowley family and many others by signing this petition to get PBS approval for a life-saving drug for those with the rare form of cancer called VHL like Levi.Fletcher's foundation Get Silly is here, if you want to buy a jumper or shirt and support spinal cord research and rehab. THE END BITS:Listen to more No Filter interviews here and follow us on Instagram here.Discover more Mamamia podcasts here.Feedback: podcast@mamamia.com.auTell us what you really think so we can give you more of what you really want. Fill out this survey and you'll go in the running to win one of five $100 gift vouchers.CREDITS:Host: Mia FreedmanYou can find Mia on Instagram here and get her newsletter here.Producers: Gia Moylan & Kimberley Braddish Audio Producer: Leah PorgesMamamia acknowledges the Traditional Owners of the Land we have recorded this podcast on, the Gadigal people of the Eora Nation. We pay our respects to their Elders past and present, and extend that respect to all Aboriginal and Torres Strait Islander cultures.Become a Mamamia subscriber: https://www.mamamia.com.au/subscribeSee omnystudio.com/listener for privacy information.

On this Monday edition of The Athletic Hockey Show, Ian and Laz discuss Laz's devil-may-care attitude about singing out loud at the supermarket, little appetite at this week's GM meetings to make change to 3-on-3 overtime, and potential PWHL expansion.Then, Down Goes Brown, Sean McIndoe, joins the show to talk about why the NHL standings are a bit of a mirage, the Panthers as the league's new love-to-hate team, and This Week in Hockey History.Plus, to close things out, Jesse Granger and the guys discuss VHL goalie Artemi Pleshkov stopping a record 124 shots in a 1-0 quintuple OT loss and how many teams could realistically win the Stanley Cup this season.Subscribe to The Athletic: http://theathletic.com/hockeyshow Hosted on Acast. See acast.com/privacy for more information.

On this Monday edition of The Athletic Hockey Show, Ian and Laz discuss Laz's devil-may-care attitude about singing out loud at the supermarket, little appetite at this week's GM meetings to make change to 3-on-3 overtime, and potential PWHL expansion. Then, Down Goes Brown, Sean McIndoe, joins the show to talk about why the NHL standings are a bit of a mirage, the Panthers as the league's new love-to-hate team, and This Week in Hockey History. Plus, to close things out, Jesse Granger and the guys discuss VHL goalie Artemi Pleshkov stopping a record 124 shots in a 1-0 quintuple OT loss and how many teams could realistically win the Stanley Cup this season. Subscribe to The Athletic: http://theathletic.com/hockeyshow Learn more about your ad choices. Visit megaphone.fm/adchoices

Spartan talks about his history in the VHL's fantasy games and TPE opportunities, along with recent Moscow trades in the S93 offseason.

Created By: Yariv Wolok & Vasili Gianarakos Music By: Jay Lubes Website: https://www.flyersnittygritty.com Like and subscribe if you want more of this content! Check Out Our Team Store: https://nitty-gritty-3.creator-spring.com/

Spartan talks about the recent tensions between NYA and MOS and other thoughts about the standings and VHL teams.

Spartan calls out who he thinks is the best player on each VHL team after about 30 games of the S92 regular season.

In this episode, Lauer Media Company President Chad Lauer and Chad Evans introduce you to the Lauer Power Podcast. Chad Lauer tells his personal story of dealing with a rare cancer disorder called Von Hippel Lindau, losing a friend and a father, and how he used that pain as fuel to do good in the world. Chad sets the stage for the podcast which will include interviews with inspirational guests, improving leadership together, and stories of entrepreneurship. 

Spartan brings on Twists and Doomsday to discuss the origins of the VHL and sim leagues, our histories in the VHL, recruitment woes and outlook, and much more!

Spartan chats about hybrid attribute ratios, the VHLE, the future of the Moscow Menace, and recruitment in the VHL

Please visit answersincme.com/XJR860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in oncology and urology discuss guideline-recommended systemic treatment options and strategies to optimize long-term care for patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC). Upon completion of this activity, participants should be better able to: Recognize unmet needs in the management of VHL disease-associated RCC; Describe the clinical impact of current guideline-recommended systemic treatment options for VHL disease-associated RCC; and Identify strategies to optimize long-term care for patients with VHL disease-associated RCC.

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 American Society of Clinical Oncology (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 in breast cancer, lymphoma, multiple myeloma, and brain tumors. First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer. You can view Dr. Henry's disclosures at Cancer.Net. Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea. In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting. The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time. It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar. Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy. There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma. You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group. In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior. This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care. In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease. And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma. In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year. ASCO: Thank you, Dr. Flowers. Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors. You can view Dr. Strowd's disclosures at Cancer.Net. Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I'm really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting. The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment. So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data. So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer. So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this. There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is. So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting. The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients. So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on. And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment. So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO. So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field. ASCO: Thank you, Dr. Strowd. 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.

Spartan catches up with life and discusses the upcoming VHL and VHLM drafts!

For the first time, I do a career task in podcast form. We chat about Nico's back story in the VHL, his upcoming depreciation and what might come in the future.

Toni Choueiri and Brian Shuch discuss Belzutifan alone and in combination for VHL syndrome and advanced sporadic RCC

Featuring perspectives from Prof Laurence Albiges, Dr Toni Choueiri and Prof Thomas Powles, moderated by Dr Brian Rini, including the following topics: •      Available Data with and Ongoing Investigation of Immune Checkpoint Inhibitors for Nonmetastatic Renal Cell Carcinoma (RCC) — Prof Powles  o   Introduction (0:00) o   Case: A woman in her early 60s after left nephrectomy (T3aN0M0 clear cell carcinoma) — Swati Vishwanathan, MD (1:39) o   Cases: A man in his early 50s develops renal dysfunction after 2 cycles of adjuvant pembrolizumab for RCC and a man in his late 60s with Stage III clear cell RCC (ccRCC) discontinues adjuvant pembrolizumab due to severe musculoskeletal pain and joint swelling — Justin Peter Favaro, MD, PhD and Priya Rudolph, MD, PhD (6:05) o   Faculty presentation: Prof Powles (11:03) •      Evidence-Based Selection of First-Line Therapy for Metastatic RCC — Dr Choueiri  o   Case: A man in his early 70s with metastatic RCC enrolls on the PDIGREE trial and receives nivolumab/ipilimumab without response followed by cabozantinib — Helen H Moon, MD (21:32) o   Cases: A man in his early 70s receives ipilimumab/nivolumab for widely metastatic RCC and develops autoimmune hepatitis and a man in his early 60s with metastatic ccRCC receives ipilimumab/nivolumab followed by nivolumab with response but develops hypothyroidism and hypoadrenalism — Victoria Giffi, MD and Philip L Brooks, MD (25:33) o   Faculty presentation: Dr Choueiri (36:38) •      Treatment Options for Relapsed/Refractory RCC — Dr Rini  o   Case: A woman in her early 60s with metastatic ccRCC receives lenvatinib/pembrolizumab but develops difficult-to-manage hypertension — Eric H Lee, MD, PhD (46:04) o   Case: A woman in her mid 60s with metastatic ccRCC and somatic VHL gene mutation receives ipilimumab/nivolumab and develops a solitary brain metastasis — Sunil Gandhi, MD (52:36) o   Faculty presentation: Dr Rini (57:54) •      Management of RCC Among Special Patient Populations — Prof Albiges  o   Case: A man in his late 60s with Waldenström macroglobulinemia and metastatic papillary RCC receives first-line ipilimumab/nivolumab followed by nivolumab but develops disease progression, including brain metastases — Nikesh Jasani, MD (1:07:58) o   Case: A woman in her early 70s with a history of psoriatic arthritis develops metastatic ccRCC, receives pembrolizumab/axitinib and develops elevated liver function tests — Georges Azzi, MD (1:12:38) o   Faculty presentation: Prof Albiges (1:18:45) CME information and select publications

Vikhaël et Jean-Raphaël Tô-Landry sont deux frères qui ont su profiter de leur talent au hockey pour voyager et vivre des expériences de vie uniques! Le premier a gravi les échelons du hockey français jusqu'à devenir la vedette de l'équipe de Brest en Ligue Magnus, alors que le second est allé enseigner en Chine pour finalement jouer en VHL, la ligue-école de la KHL ! Les anecdotes se succèdent dans cette superbe conversation avec les deux frères complices !Viens voir le spectacle en rodage de ce cher hurluberlu de David, lui qui sera à Montréal le 17 mars, à Longueuil le 19 mai et nouvelle date à Québec le 13 septembre! Procure-toi tes billets au davidbeaucage.com !Vous voulez faire connaître votre marque / entreprise? Ayez votre propre pub sur Drette su'l tape pour rejoindre votre communauté! Écrivez à thomas@drettesultape.com pour plus de détails! Hosted on Acast. See acast.com/privacy for more information.

The Hamilton Today Podcast with Scott Radley: The downbound lanes of the Claremont have been closed amid concerns of erosion. What brought this on. A meeting was held last night between HDSB, parents and stakeholders about the situation at Oakville Trafalgar high school and the status of the dress code policy. With this new health care deal, how will it impact doctors and the care you receive? The NHL trade deadline comes tomorrow. Where do Canada's teams stand? A survey done on behalf of the Canadian Organization for Rare Disorders has found that many Canadians living with rare diseases struggle for years to access care. It is all coming up on the Hamilton Today Podcast! Guests: Jackie Kennedy, Director, Engineering Services. Murray Costello, Director, Southeast Region Operations, Enbridge Gas. Sheba Siddiqui, Producer and On Air Co-ordinator for Toronto Today. Dr. Mekalai Kumanan, President of the Ontario College of Family physicians and family doctor in Cambridge. Duff Conacher, Co-Founder of Democracy Watch. Ryan Kennedy, Senior Writer, The Hockey News. Stephanie Gandulla, maritime archaeologist and the Resource Protection Coordinator for NOAA's Thunder Bay National Marine Sanctuary. Matt Francis. Ward 5 City Councillor, City of Hamilton. Steve Parrott, has two adult daughters with VHL disease and he serves as the Board Chair for the Canadian VHL Alliance. Grace Tong is the Vice President & Equity, Diversity and Inclusion Practice Lead, Ipsos Public Affairs, Canada. Host – Scott Radley Content Producer – Elizabeth Russell Technical/Podcast Producer – William Webber Podcast Co-Producer – Tom McKay News Anchor – Dave Woodard & Jennifer McQueen Want to keep up with what happened in Hamilton Today? Subscribe to the podcast! https://megaphone.link/CORU8835115919

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530413v1?rss=1 Authors: Myszczyszyn, A., Popp, O., Kunz, S., Sporbert, A., Jung, S., Penning, L. C., Fendler, A., Mertins, P., Birchmeier, W. Abstract: Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established organoids from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that the organoids resembled renewal of adult kidney tubular epithelia, since organoid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-{beta}-catenin-GOF together with Notch-GOF and Wnt-{beta}-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of {beta}-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the organoid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode of BackTable Urology, Dr. Aditya Bagrodia, Dr. Ari Hakimi (Memorial Sloan Kettering Cancer Center), and Dr. Nirmish Singla (Johns Hopkins University), discuss the value and indications for germline testing in renal cell carcinoma (RCC). --- SHOW NOTES First, the doctors explain basic information about germline mutations and kidney cancer. Although historical data has shown that 5% of kidney cancers are inherited, recent efforts to increase testing through commercial testing and large scale efforts at cancer centers have proven that 8-10% of kidney cancers are inherited. Von Hippel Lindau (VHL) syndrome is the most prototypical kidney cancer predisposition syndrome, but there are other less common ones as well. Extrarenal manifestations of VHL syndrome include pancreatic tumors, pancreatic cysts, pheochromocytomas, retinoblastomas, and CNS hemangioblastomas. These tumors have a variable penetrance, but African Americans and women are more likely to have hereditary RCC. The doctors recommend asking newly diagnosed RCC patients about a broad spectrum of their family history that includes cancer and non-malignant conditions, such as uterine leiomyomata. Dr. Hakimi notes that some patients will confuse germline testing with somatic tumor testing, so urologists will have to explain to patients that the VHL mutation was found in their tumor, not in their blood or saliva. Extended physical exams to look for syndromic conditions can also be performed. A thorough cutaneous exam to look for fibrofolliculomas, leiomyomas, facial angiofibromas, and cafe-au-lait spots can help indicate the presence of a familial syndrome. According to guidelines, all patients diagnosed with RCC under 46 years of age should be recommended to have germline testing. Dr. Bagrodia mentions that having experienced genetic counselors and setting up thorough dot phrases to send to patients explaining their results is helpful for him. Dr. Singla adds that medical geneticists have the ability to counsel the patients more extensively on the risks and benefits of giving consent to go forward with genetic testing. They can also provide psychosocial support and education for the patients. The doctors then move on to discuss how germline mutations may lead to different treatment modalities. Precision surgery, or utilizing pretest probability information about a tumor to guide surgical approach, may be possible with germline testing. Additionally, testing may help surgeons to decide whether to perform a retroperitoneal lymph node dissection (RPLND). Next, the doctors discuss belzutifan, which is an oral drug used to treat VHL familial syndrome tumors. Finally, they discuss the use of tumor sequencing for research purposes and share what they are most excited for in the field of RCC research.

Dr Glenn McConell chats with Professor Grégoire Millet from the University of Lausanne in Switzerland. He is an absolute world leader in research into altitude training and hypoxic conditioning. This area has progressed greatly from Live High-Train High (LHTH) to Live High-Train Low (LHTL), LLTH and LHTL (and High). The type of attitude training/hypoxic conditioning one would undertake depends on if training for endurance or team sports. We also discussed using low oxygen (hypoxia) and high oxygen (hyperoxia) for health benefits. 0:00. Introduction and Grégoire's background 4:58. History of altitude training 6:52. Many combinations of altitude training LHTH, Live High-Train Low (LHTL), LLTH, LHTL (and High) 9:45. Altitude and oxygen availability 12:45. Altitude vs breathing low oxygen: not the same 14:32. Immediate responses to hypoxia 20:12. Lower VO2 max at altitude 24:39. Absolute vs relative exercise intensity 25:46. Placebo effect? 28:45. Long-term responses to altitude 32:24. Need to exercise for optimal adaptations in muscle 33:34. LHTL 36:19. LLTH 41:34. Health effects of LLTH 43:04. Repeated sprints in hypoxia (RSH) 45:29. LLTH and improved blood vessel function 47:54. Health effects of low and high oxygen 54:50. Hypoventilation at low lung volume (VHL) to cause hypoxia 59:00. VO2 max training at altitude 1:00:55. Use more carbohydrate during exercise at altitude 1:02:30. Greater sympathetic activation (adrenaline etc) at altitude 1:04:52. Oxidative stress/ Reactive oxygen species 1:08:42. What doesn't kill you makes you stronger 1:10:12. Manipulating repeated sprints duration to alter aerobic/anaerobic contributions 1:13:20. Specificity of training to achieve required outcomes 1:13:51. LHTL (and High) in Rugby players 1:17:40. LHTL and LHTL (and High) for endurance 1:19:09. Ultramarathon star Killian Jornet and altitude training 1:21:15. Controversies in the area 1:24:47. Health benefits the most exciting for him 1:25:37. Outro (9 secs) Inside Exercise brings to you the who's who of exercise metabolism, exercise physiology and exercise's effects on health. With scientific rigor, these researchers discuss popular exercise topics while providing practical strategies for all. The interviewer, Emeritus Professor Glenn McConell, has an international research profile following 30 years of Exercise Metabolism research experience while at The University of Melbourne, Ball State University, Monash University, the University of Copenhagen and Victoria University. He has published over 120 peer reviewed journal articles and recently edited an Exercise Metabolism eBook written by world experts on 17 different topics (https://link.springer.com/book/10.1007/978-3-030-94305-9). Connect with Inside Exercise and Glenn McConell at: Twitter: @Inside_exercise and @GlennMcConell1 Instagram: insideexercise Facebook: Glenn McConell LinkedIn: Glenn McConell https://www.linkedin.com/in/glenn-mcconell-83475460 ResearchGate: Glenn McConell Email: glenn.mcconell@gmail.com Subscribe to Inside exercise: Apple Podcasts: https://podcastsconnect.apple.com/my-podcasts/show/inside-exercise/03a07373-888a-472b-bf7e-a0ff155209b2 YouTube https://www.youtube.com/channel/UChQpsAQVEsizOxnWWGPKeag Spotify Google Podcasts Anchor Podcast Addict Etc

Spartan talks about recent changes to VHL depreciation, comments around moderation, the VHL playoff race and the state of the VHLM.

Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome caused by mutations in the VHL gene. These mutations predispose patients to the development of cysts and tumors in several systems and organs, including the central nervous system, retina, kidneys, pancreas, adrenal glands and reproductive organs. VHL is a complex disease that requires specialized advanced treatment from a multidisciplinary team of specialists.In this Better Edge podcast episode, the following experts from the Northwestern Medicine Von Hippel-Lindau Disease Program discuss VHL and the clinical management for this patient population: Rimas V. Lukas, MD, Associate Professor of Neuro-Oncology; Niraj K. Shenoy, MD, PhD, MS, Associate Professor of Hematology/Oncology and of Pathology; and Brittany M. Szymaniak, PhD, CGC, Instructor of Urology. They share a recent Northwestern Medicine study published in Neuro-Oncology that examined belzutifan, the first approved HIF-2α inhibitor, in VHL-associated tumors.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.11.511735v1?rss=1 Authors: Elcocks, H., Brazel, A. J., McCarron, K. R., Kaulich, M., Husnjak, K., Mortiboys, H. J., Clague, M. J., Urbe, S. Abstract: The selective autophagy of mitochondria is linked to mitochondrial quality control and is critical to a healthy organism. We have conducted a CRISPR/Cas9 screen of human E3 ubiquitin ligases for influence on mitophagy under both basal cell culture conditions and following acute mitochondrial depolarisation. We identify two Cullin RING ligases, VHL and FBXL4 as the most profound negative regulators of basal mitophagy. We show that these converge through control of the mitophagy adaptors BNIP3 and BNIP3L/NIX through different mechanisms. FBXL4 suppression of BNIP3 and NIX levels is mediated via direct interaction and protein destabilisation rather than suppression of HIF1-mediated transcription. Depletion of NIX but not BNIP3 is sufficient to restore mitophagy levels. Our study enables a full understanding of the aetiology of early onset mitochondrial encephalomyopathy that is supported by analysis of a disease associated mutation. We further show that the compound MLN4924, which globally interferes with Cullin RING ligase activity, is a strong inducer of mitophagy providing a research tool in this context and a candidate therapeutic agent for conditions linked to mitochondrial dysfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Episode 105: Renal Cell Carcinoma. Manpreet and Jon-Ade explain how to diagnose renal cell carcinoma. Introduction about age and kidney transplant by Dr. Arreaza and Dr. Yomi. Introduction: Too old for a new kidney?By Hector Arreaza, MD. Discussed with  Timiiye Yomi, MD.Today we will be talking about the kidneys, those precious bean-shaped organs that detoxify your blood 24/7. Amazingly, we can live normal lives with one kidney, but when the kidney function is not good enough to meet the body's demands, patients need to start kidney replacement therapy. Modern medicine has made a lot of advances with dialysis, but the perfection of a kidney has not been outperformed by any machine yet. That's why kidney transplant is the hope for many of our patients with end-stage kidney disease.The need for a kidney transplant is growing, likely due to increasing chronic diseases such as diabetes and hypertension, and also because of an increase in elderly population. About 22% of patients on the kidney transplant waiting list are over age 65. A cut-off age to receive kidney transplant has not been established across the globe. Different countries use different criteria for the maximum age for transplant. The American Society of Transplantation's guidelines states “There should be no absolute upper age limit for excluding patients whose overall health and life situation suggest that transplantation will be beneficial.” So, if your patient is older than 65 and needs a kidney, they may qualify for a transplant, and age should not be an absolute contraindication to receive it. Actually, older patients may have lower risk of rejection due to a theoretically weaker immune system. A live donor is likely to be a better option for elderly patients. A condition that would make your elderly patient a poor candidate for kidney transplant would be frailty. Common contraindications to kidney transplant include active infections or malignancy, uncontrolled mental illness, ongoing addiction to substances, reversible kidney failure, and documented active and ongoing treatment nonadherence.So, remember to take these factors into consideration when deciding if you need to refer your elderly patients for a kidney transplant, there is no such thing as being too old for a new kidney if your patient meets all the criteria for a transplant.This is Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care physician for additional medical advice. Renal Cell Carcinoma. By Manpreet Singh, MS3, Ross University School of Medicine, and Jon-Ade Holter, MS3 Ross University School of Medicine. Moderated by Hector Arreaza, MD. Definition:Renal cell carcinoma is a primary neoplasm arising form the renal cortex. 80-85 percent of renal tumors are renal cell carcinomas followed closely by transitional cell renal cancer and Wilms tumor.  Epidemiology: In 2022, 79,000 new cases of kidney cancer were diagnosed with almost 14,000 mortalities. There is a 2:1 male to female ratio and the average age is 64 and normally 65-74. African Americans and American Indians have a higher prevalence rate compared to other racial groups. The lifetime risk for developing kidney cancer in men is about 1 in 46 (2.02%) and 1 in 80 (1.03%) in women.  Risk Factors associated with RCC: Anything that causes assault to the kidneys and affects its function would cause increased demand, injury, and inflammation. This assault can lead to cell derangement and lead to cancer. The risk factors that have been associated with RCC are smoking, obesity, HTN, family history of kidney cancer, Trichloroethylene (a metal degreaser used in large manufacturing factories), acetaminophen, and patients with advanced kidney disease needing dialysis. Patients with syndromes that cause multiple types of tumors: VHL (von Hippel-Lindau) deficiency, a tumor suppressor, gives rise to clear cell renal cell carcinoma. Familial inheritance of VHL deficiency is mostly found in patients that have RCC at a very young age, before 40 y/o. Other tumors can be found in the eye, brain, spinal cord, pancreas, and pheochromocytomas.Hereditary leiomyoma-renal cell carcinoma due to FH gene mutations causing women who have leiomyomas to have a higher risk of developing papillary RCC.Birt-Hogg-Dube (BHD) syndrome mutation in FLCN gene who develop various skin and renal tumors.Cowden syndrome is a mutation in the PTEN gene giving rise to cancers associated with breast, thyroid , and kidney cancers.Tuberous sclerosis causes benign tumors of the skin, brain, lungs, eyes, kidneys, and heart. Although kidney tumors are most often benign, occasionally they can be clear cell RCC. Screening For RCC:Screening is unnecessary because of the low prevalence of this cancer in the general population, though certain groups require annual repeat imaging via US, CT, or MRI. Inherited conditions that are associated with RCC such as VHL syndrome or Tuberous SclerosisESRD patients who have been on dialysis for 3-5 yearsFamily history of RCCPrior kidney irradiation Clinical Picture: Most patients with RCC are asymptomatic until cancer grows large enough to cause disruption of local organs, such as the kidney, bladder, or renal vein, and dysregulates other organs via metastasis. Therefore, it's important to look at other signs and symptoms caused by RCC.  The patient most likely will be an older male who presents with the classic triad of: Flank pain: caused by rapid expansion and stretching of the renal capsule.Hematuria: occurs from the invasion of the neoplasm into the collecting duct.Palpable abdominal mass: mass tends to be homogenous and mobile with respirations. Though this presents only in 9% of patients during the presentation, having physical symptoms is a sign of advanced disease and 25% of patients with these signs tend to have distant metastasis.  Anemia: normally associated with anemia of chronic disease. It precedes the disease by at least 8 months to 1 year. Males can develop varicoceles because of decreased emptying due to neoplasm obstruction. Patients normally develop varicoceles on the left due to the spermatic vein emptying in the higher resistance left renal vein, which causes backup of the blood in the pemphigus plexus. Though a right-sided varicocele should raise a higher suspicion of obstruction due to the spermatic vein draining directly into the IVC which is lower in resistance. A right-sided varicocele is seen in approximately 11 percent of patients. The paraneoplastic syndrome can also arise from RCCEpo: Erythrocytosis with symptoms of weakness, fatigue, headache, and joint pain.PTHrP: PTH-related peptide acts like PTH which gives rise to hypercalcemia with the prevalent symptoms of arthritis, osteolytic lesions, confusions, tetany, ventricular tachycardia, shortened QTc, and nausea and vomiting.Renin: overproduction from the juxtaglomerular cells can cause disarrangement of the RAAS system causing hypertension.Others also like ACTH and beta-HCG. Other disorders present include hepatic dysfunction, cachexia, secondary amyloidosis, and thrombocytosis. Workup If a patient comes in with painless hematuria, then the first test should be abdominal CT or abdominal ultrasound. A CT is more sensitive than the US but it can quickly indicate if the abdominal mass felt can be a cyst or a solid tumor.  US of kidneys should show if it's a simple cyst:-The cyst is round and sharply demarcated with smooth walls- It's anechoic – appears solid black-There is a strong posterior wall echo-Use the Bosniak classification to classify mass  Bosniak I: benign simple cyst with thin wall less than equal to 2mm, no septa or calcifications. No future workup is needed. Bosniak II: benign cyst, 3 cm diameter, requires f/u with US/CT/MRI at 6 months, 12 months, and annually for the next 5 years. Chance of malignancy: 5%.  Bosniak III: indeterminate cystic mass with thick, irregular or smooth walls. This requires nephrectomy or radiofrequency ablation. Chance of malignancy: 55%  Bosniak IV: Clearly a malignancy its grade III with enhancing soft tissue components that its independent from the wall or septum. Requires total or partial nephrectomy. Chance of malignancy 100%.  CT of the kidneys for a neoplasm should show:-Thickened irregular walls or septa -Enhancement after contrast injection are suggestive of malignancy-CT can also help detect invasion in local tissue areas such as renal vein and perinephric organs  MRI is used if the patient cannot use contrast or kidney function is poor. MRI can also evaluate the growth of the cancer. Other imaging studies:Other imaging studies that may be useful for assessing for distant metastases include bone scan, CT of the chest, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Treatment and staging Nephrectomy, partial or total, will be used as the initial tissue collection for pathology. If the patient is not a surgical candidate, you can also obtain a percutaneous biopsy. The nephrectomy is preferred because first, it serves as a definitive treatment option, but also it allows for definitive staging of the cancer with tumor and nodal staging. Regardless of the size, any solid mass may indicate malignancy and point towards RCC, requiring resection.   TNM staging Stage I: Tumor is 7cm across or smaller and only in the kidney with no lymph nodes or distant mets. T1N0M0 Stage IIa: Tumor size is larger than 7cm but still in the kidney but no invasion of lymph node or mets. T2N0M0 Stage IIb: Tumor is growing into the renal vein or IVC, but not into neighboring organs such as adrenals or Gerota's fascia and still lacks lymph node invasion and mets. T3N0M0.  Stage III: Tumor can be any size but has not invaded outside structures such as adrenals, though nearby lymph node invasion is present but not distant. There is no distant mets. T3N1M0. Stage IV:  The main tumor is beyond the Gerota's fascia and may grow into the adrenal gland . It may or may not spread to the lymph nodes or may not have distant mets. Stage IV also consists of any cancer that has any number of distant mets. T4 Adjuvant therapy can be done with immune therapy. Conclusion: Now we conclude our episode number 105 “Renal cell carcinoma.” This type of cancer may be asymptomatic until it is large enough to cause symptoms. Keep it on your list of differentials on patients with hematuria, flank pain, weight loss, and abnormal imaging. Keep in mind the features of simple kidney cysts vs complex cysts when assessing kidney ultrasounds. Your patient will be grateful for an early diagnosis of RCC and a prompt treatment. Even without trying, every night you go to bed being a little wiser.This week we thank Hector Arreaza, Timiiye Yomi, Manpreet Singh, Jon-Ade Holter. Thanks for listening to Rio Bravo qWeek Podcast. If you have any feedback, contact us by email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. Audio edition: Suraj Amrutia. See you next week!  Bibliography: Is There a Cut Off Age for Kidney Transplant?, Mayo Clinic Connect, Jul 18, 2017, https://connect.mayoclinic.org/blog/transplant/newsfeed-post/is-there-a-cut-off-age-for-kidney-transplant/ Atkins, Michael. “Clinical Manifestations, Evaluation, and Staging of Renal Cell Carcinoma.” UpToDate, January 21. https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-staging-of-renal-cell-carcinoma American Cancer Society. “Key Statistics About Kidney Cancer”. Cancer.Org, 2022, https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Grünwald V, Gillessen S, Horwich A; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019 May 1;30(5):706-720. doi: 10.1093/annonc/mdz056. PMID: 30788497. https://pubmed.ncbi.nlm.nih.gov/30788497/. Gaillard, F., Bell, D. Bosniak classification system of renal cystic masses. Reference article, Radiopaedia.org. (accessed on 20 May 2022) https://doi.org/10.53347/rID-1006. Kopel J, Sharma P, Warriach I, Swarup S. Polycythemia with Renal Cell Carcinoma and Normal Erythropoietin Level. Case Rep Urol. 2019 Dec 11;2019:3792514. doi: 10.1155/2019/3792514. PMID: 31934488; PMCID: PMC6942735. https://pubmed.ncbi.nlm.nih.gov/31934488/. Leslie SW, Sajjad H, Siref LE. Varicocele. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448113/. Maguire, Claire. “Understanding Endoscopic Ultrasound and Fine Needle Aspiration.” Educational Dimension, Educational Dimensions, 1 Jan. 2007, educationaldimensions.com/eLearn/aspirationandbiopsy/eusterm.php. Maller, V., Hagir, M. Renal cell carcinoma (TNM staging). Reference article, Radiopaedia.org. (accessed on 20 May 2022) https://doi.org/10.53347/rID-4699. Palapattu GS, Kristo B, Rajfer J. Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. Rev Urol. 2002 Fall;4(4):163-70. PMID: 16985675; PMCID: PMC1475999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475999/.

Spartan got his COVID booster and rambles about 15 years of the VHL incoherently.

Well, this just happened. I was going to record a solo podcast for the VHL (that's right PBE, I'm cheating on you) but I did it in a public channel and a bunch of PBE folks hopped in and PBE stuff happened so that is that. I apologize for nothing, but also I apologize for everything. Eso Diesel DRJ LSUFan101

Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute.  Transcript:  Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News.  My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia.  Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. 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.org/podcast.  Jeanny, it is great to have you on the podcast today.  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well.  Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.”  So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria.  Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics.  So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588.  Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics.  The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset.  Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues?  Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers.  Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.”  Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract?  Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy.  However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma.  The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States.  Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute.  Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract?  Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings.  So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics.  Dr. Jeanny Aragon-Ching: Agree. Yeah.  Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road.  So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.”  So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting?  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery.  So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence.  So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment.  What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans.  Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival.  Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial?  Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy.  Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future.  Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer.  Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.”  During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer.  What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer.  And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy.  So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression.  Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time.  Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us?  Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients.  Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression.  Dr. Jeanny Aragon-Ching: I agree with that.  Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments.  So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC.  So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC.  So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression.  The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia.  There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals.  Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners?  Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway.  Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting.  Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, 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 podcast.    Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis  Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics  Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma  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 expressed 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.       

 Welcome to this episode of Physician's Weekly Podcast. My name is Dr. Rachel Giles, from Medicom Medical Publishers, in collaboration with Physician's Weekly. There was a lot of interesting medical news this last week. Later in this episode, we interview Dr. Samer Al Hadidi, from Little Rock, Arkansas, who the lead author of a study about the lack of enrollment of African-American patients into trials in general, and here in particular, trials that were used to register the use of CAR-T cell therapies for the treatment of various hematological malignancies. He presents some interesting solutions that can be applicable to all trials.   Also in this episode of Physician's Weekly Podcast, we speak to our regular contributor, who goes by the pseudonym, Dr. MedLaw all about what “Causality” means in the courtroom.  When is a doctor the cause of a medical problem, and what can be done about it?But first, Physician's Weekly speaks with Dr. Eric Jonasch, from the University of Texas MD Anderson Hospital in Houston, about  the results of the his recently published New England Journal of Medicine article reporting the registrational data for a small molecule belzutifan in patients with the rare tumor syndrome von Hippel-Lindau disease, abbreviated as VHL. I have had the distinct honor of knowing hundreds of VHL patients over the last 20 years, and this study has truly become a landmark breakthrough for patients dealing with tumors in their kidneys, pancreas, adrenal glands, brain or spinal cord, eyes, endolymph sacs, epididymis, or broad ligament.  It was FDA approved in August 2021, and the patient  and medical VHL community is so relieved to have a systemic treatment finally.Enjoy listening! More reading:  Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425. PMID: 34818478. Al Hadidi S, Dongarwar D, Salihu HM, Kamble RT, Lulla P, Hill LC, Carrum G, Ramos CA, Heslop HE, Usmani SZ. Health disparities experienced by Black and Hispanic Americans with multiple myeloma in the United States: a population-based study. Leuk Lymphoma. 2021 Dec;62(13):3256-3263. doi: 10.1080/10428194.2021.1953013. Epub 2021 Jul 18. PMID: 34278937.Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Please listen to this podcast - I had a MASSIVE ah-ha moment in the middle of what and why work/life balance is backwards! Plus, Victoria talks about what style means for women and how she has found her destiny. Victoria Hamilton from VHL - https://www.victoriahamiltonlifestyle.co.uk/ MEMBERSHIP To join the Shine On You Crazy Daisy Membership and invest in the growth of your business, please click here to find out more. You will receive knowledge to grow your business and support to implement what you learn, putting time aside to work ON your business - and have FOCUSED-FUN whilst doing it! BOOKS To buy Shine On You Crazy Daisy – Volume 1, 2, 3, 4 & 5: Visit Amazon, iBooks or any good book retailer. YOUTUBE PODCAST EPISODES To watch our podcast episodes on Youtube - CLICK HERE.

In this episode, Joseph and Aaron discuss the idea of Victim-Survivor-Navigator; a concept that has helped Joseph to acknowledge the changes and adaptations necessary to navigate life with von Hippel Lindau.Later in the show, we're joined by special guest, Chandra Clark, executive director of the VHL Alliance. Chandra helps us shed light on this shared path from circumstance and trauma to recovery and a return to living our hero's journey.For more information on the VHL Alliance visit VHL.org

Welcome to Very Heroic Living. In this pilot episode, host Joseph Heisler introduces himself and his journey living with von Hippel-Lindau aka VHL. Diagnosed at a young age, Joseph has been through many stages of life having to navigate extraordinary circumstances for himself and his family. Joined by an old friend and show producer, Aaron Hodges, Joseph opens up about some of the dark days and experiences that have shaped his life and how he manages a lifestyle he never imagined.

Here are the links for everything discussed in Episode 67. Times are also below so feel free to skip around and get to the drugs that interest you. And I apologize for the echo - need to find a better place to record in the new home :) (1:18) COVID19 vaccine approved as brand name Comirnaty (8:10) Amended EUA for COVID vaccines (10:20) Welireg approved for VHL Connect with The Rx Daily Dose:Twitter      Instagram      YouTube      Linkedin       WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter       Instagram       Linkedin  ★ Support this podcast on Patreon ★

Chandra Clark the Executive Director at the VHL Alliance swings by to help increase our awareness of the rare chronic disease: VHL or von Hippel-Lindau disease. Take a listen to learn how this disease effects individuals, how the alliance is helping and how you can help.