Podcasts about accommodations

Food allergy accommodations don't stop at the classroom door—they extend into workplaces, public spaces, and even stadiums. But what rights do you actually have? Today, we're joined by FAACT's General Counsel, Amelia Smith, JD, to break it all down and help you understand your civil rights.Resources to keep you in the know:FAACT's Accommodations Resource CenterFAACT's Civil Rights Advocacy Resource CenterFAACT's Local ResourcesContact Amelia Smith, JD: Amelia.Smith@FoodAllergyAwareness.orgYou can find FAACT's Roundtable Podcast on Apple Podcasts, Pandora, Spotify, Podbay, iHeart Radio, or wherever you listen to podcasts.Follow us on Facebook, Instagram, BlueSky, Threads, LinkedIn, Pinterest, TikTok, and YouTube.Sponsored by: DBV TechnologiesThanks for listening! FAACT invites you to discover more exciting food allergy resources at FoodAllergyAwareness.org!

When someone becomes a victim of a crime, a long and often overwhelming process towards justice begins. It can be extremely difficult and taxing for anyone but when people with disabilities, especially those with intellectual/developmental disabilities (IDD), enter this process, barriers and systemic failures might mean that they never get to see the justice they deserve. This documentary exposes these failures through the lens of advocacy and victim support providers.

Leah Stiegler, a seasoned labor attorney from Woods Rogers, delves into the complexities of modern workplace dynamics. From handling toxic personalities to navigating the intricacies of non-compete agreements, Leah offers invaluable insights for employers. She discusses the importance of maintaining a psychologically safe environment and the role of documentation in protecting both employees and employers. Leah also touches on the ethical use of AI in workplace management, emphasizing transparency and responsible practices. Tune in to learn how to manage workplace challenges effectively and keep your organization legally compliant. Whether you're dealing with workplace toxicity or exploring AI's role in sales, Leah's expertise is a must-listen for all managers. "I would say that the best advice I can give on that is for managers to address concerns early on, to hear someone out regardless of whether they think the concern is ridiculous or whether they know that the person is wrong about their perception, whatever it may be." - Leah Stiegler KEY TAKEAWAYS: -How can managers handle false allegations without appearing retaliatory? -The importance of handling workplace HR legal issues promptly -The latest unusual workplace HR trends and accommodations, including furries, litter boxes and other requests -Non-Compete agreements -What to do about workplace romances and the various dynamics and scenarios of those -AI, technology forensic data, social media posts legal latest #HR #humanresources #businesslaw #law #lawyer #laborlaw #laborattorney #HRattorney #workplaceaccommodations CONNNECT WITH LEAH STIEGLER www.woodsrogers.com https://www.linkedin.com/in/leah-stiegler-28aa7a62/ https://www.linkedin.com/company/woodsrogers/ Connect with Manage Smarter         Website: https://salesfuel.com/manage-smarter/·         LinkedIn: https://www.linkedin.com/in/audreystrong/                                                 LinkedIn: https://www.linkedin.com/in/cleesmith/ X Audrey https://x.com/tallmediamaven Lee  https://x.com/cleesmith  Connect with SalesFuel·         Website:  https://salesfuel.com/·         X: https://x.com/SalesFuel·         Facebook: https://www.facebook.com/salesfuel/ Learn more about your ad choices. Visit megaphone.fm/adchoices

In this inspiring episode of Converge Autism Radio, we sit down with Jonathan, a 10-year-old navigating life with both autism and ADHD. Together with his family, he shares honest reflections on medication, school testing, sports, and the importance of making his own choices. From learning how to balance focus and independence to discovering the life-changing role of a positive mindset, Jonathan reminds us that empowerment starts early—and that children thrive when they're trusted with agency. This episode offers parents, educators, and clinicians practical insight into supporting kids with accommodations while also celebrating their strengths.A shout out to NeuroFM for sharing this amazing story with us! Jwww.springbrookbehavioral.comwww.convergeautism.comwww.allabilitiesnofilter.com

This podcast is an in-depth and fascinating conversation with educational psychologist Dr. Claire Yorke on accommodations within the IEB (Independent Examinations Board). We delve into what accommodations are available, what they are used for, and how they are applied to help learners achieve their best academic potential. Claire Yorke has a longstanding relationship with Edu Inc (Education Incorporated) and has helped many of our students with the assessments and applications for accommodations. We value her professionalism, and we thought it would be great for her to share her insights and understanding of this sometimes daunting process. EduInc website · Facebook (Public) · Facebook (closed group) · Twitter (closed group) · YouTube · Review us on Google

Dr. Sumanta (Monty) Pal and Dr. Petros Grivas discuss innovative new intravesical therapies and other recent advances in the treatment of non-muscle invasive bladder cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello and welcome. I'm Dr. Monty Pal here at the ASCO Daily News Podcast. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. And I'm really delighted to be your new host here. Today's episode is going to really sort of focus on an area near and dear to my heart, something I actually see in the clinics, and that's bladder cancer. We're specifically going to be discussing non-muscle invasive bladder cancer, which actually comprises about 75% of new cases. Now, in recent years, there's been a huge shift towards personalized bladder-preserving strategies, including innovative therapies and new agents that really are reducing reliance on more primitive techniques like radical cystectomy and radiation therapy. And I'm really excited about this new trend. And really at the forefront of this is one of my dear friends and colleagues, Dr. Petros Grivas. He's a professor in the Department of Medicine and Division of Hematology Oncology at the University of Washington. It's going to take a while to get through all these titles. He's taken on a bunch of new roles. He is medical director of the International Program, medical director of the Local and Regional Outreach Program, and also professor in the Clinical Research Division at the Fred Hutch Cancer Center. Petros, welcome to the program. Dr. Petros Grivas: Thank you so much, Monty. It's exciting for me to be here. Dr. Sumanta (Monty) Pal: Just FYI for our audience, our disclosures are available in the transcript of this episode.  We're going to get right into it, Petros. Non-muscle invasive bladder cancer, this is a really, really challenging space. We see a lot of recurrence and progression of the disease over time, about 50% to 70% of patients do have some recurrence after initial treatment, and about 30% are ultimately going to progress on to muscle-invasive or metastatic disease. Now, I will say that when you and I were in training, non-muscle invasive bladder cancer was something that was almost relegated to the domain of the urologist, right? They would use treatments such as BCG (Bacillus Calmette-Guérin) in a serial fashion. It was rare, I think, for you and I to really enter into this clinical space, but that's all changing, isn't it? I mean, can you maybe tell us about some of the new therapies, two or three that you're really excited about in this space? Dr. Petros Grivas: Monty, you're correct. Traditionally and conventionally, our dear friends and colleagues in urology have been managing patients with non-muscle invasive bladder cancer. The previous term was superficial bladder cancer. Now, it has changed, to your point, to non-muscle invasive bladder cancer. And this has to do with the staging of this entity. These tumors in superficial layers of bladder cancer, not invading the muscularis propria, the muscle layer, which makes the bladder contract for urine to be expelled. As you said, these patients have been treated traditionally with intravesical BCG, one of the oldest forms of immunotherapy that was developed back in the 1970s, and this is a big milestone of immunotherapy development. However, over the years, in the last 50 years, there were not many options for patients in whom the cancers had progression or recurrence, came back after this intravesical BCG. Many of those patients were undergoing, and many of them still may be undergoing, what we call radical cystectomy, meaning removal of the bladder and the lymph nodes around the bladder. The development of newer agents over the last several years has given the patients the option of having other intravesical therapies, intravesical meaning the delivery of drugs, medications inside the bladder, aiming to preserve the bladder, keep the bladder in place. And there are many examples of those agents. Just to give you some examples, intravesical chemotherapy, chemotherapy drugs that you and me may be giving intravenously, some of them can be given inside the bladder, intravesical installation. One example of that is a combination of gemcitabine and docetaxel. These drugs are given in sequence one after the other inside the bladder, and they have seen significant efficacy, good results, again, helping patients keeping the bladder when they can for patients with what we call BCG unresponsive non-muscle invasive bladder cancer. And again, there's criteria that the International Bladder Cancer Group and the FDA developed, how to define when BCG fails, when we have BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: And we're actually going to get into some of the FDA requirements and development pathways and so forth. What I'm really interested in hearing, and I'm sure our audience is too, are maybe some of the new intravesical treatments that are coming around. I do think it's exciting that the gemcitabine and docetaxel go into the bladder indeed, but what are some of the top new therapies? Pick two or three that you're excited about that people should be looking out for in this intravesical space. Dr. Petros Grivas: For sure, for sure. In terms of the new up-and-coming therapies, there are a couple that come to mind. One of them is called TAR-200, T-A-R 200. This agent is actually a very interesting system. It's an intravesical delivery of a chemotherapy called gemcitabine, the one that I just mentioned a few minutes ago, that is actually being delivered through what we call a pretzel, which is like a rounded [pretzel-shaped] structure working like an osmotic pump, and that is being delivered inside the bladder intravesically by urologists. And this drug is releasing, through the osmotic release mechanism, this chemotherapeutic drug, gemcitabine, inside the bladder. And this can be replaced once every 3 weeks in the beginning. And the data so far from early-phase trials are really, really promising, showing that this agent may be potentially regulatory approved down the road. So TAR-200 is something to keep in mind. And similarly, in the same context, there is a different drug that also uses the same mechanism, and this osmotic release, this pretzel, it's just encoded with a different agent. The different agent is an FGFR inhibitor, a target therapy called erdafitinib, a drug that you and me may give in patients with metastatic urothelial carcinoma if they have an FGFR3 mutation or fusion. And that drug is called TAR-210. Dr. Sumanta (Monty) Pal: And can I ask you, in that setting, do you have to have an FGFR3 mutation to receive it? Or what is the context there? Dr. Petros Grivas: So for TAR-210, TAR-2-1-0, usually there is a checking to see if there is an FGFR3 mutation or fusion. And the big question, Monty, is do we have adequate tissue, right? From a limited tissue on what we call the TURBT, right, that urologists do. And now there is a lot of development in technology, for example, urine circulating tumor DNA to try to detect these mutations in the urine to see whether the patient may be eligible for this TAR-210. Both of those agents are not FDA approved, but there are significant promising clinical trials. Dr. Sumanta (Monty) Pal: So now let's go to a rapid-fire round. Give us two more agents that you're excited about in this intravesical space. What do you think? Dr. Petros Grivas: There is another one called cretostimogene. It's a long name. Dr. Sumanta (Monty) Pal: They really make these names very easy for us, don't they? Dr. Petros Grivas: They are not Greek names, Monty, I can tell you, you know. Even my Greek language is having trouble pronouncing them. The cretostimogene, it's actually almost what we call a growth factor, a GM-CSF. The actual name of this agent is CG0070. This is a replicating mechanism where GM-CSF is replicating in cells. And this agent has shown significant results again, like the TAR-200, in BCG unresponsive non-muscle invasive bladder cancer. I would say very quickly, two agents that actually were recently approved and they're already available in clinical practice, is nadofaragene firadenovec, another long name. That's a non-replicating vector that has the gene of interferon alfa-2b that stimulates the immune system in the bladder. It's given once every 3 months. And the last one that was, as I mentioned, already FDA approved, it's an interleukin-15 superagonist. It's another long name, which is hard to pronounce, but I will give it a try. It's a drug that was recently actually approved also in the UK. The previous name was N-803. It's given together with BCG as a combination for BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: This is a huge dilemma, I think, right? Because if you're a practicing, I'm going to say urologist for the moment, I guess the challenge is how do you decide between an IL-15 superagonist? How do you decide between a pretzel-eluting agent? How do you decide between that and maybe something that's ostensibly, I'm going to guess, cheaper, like gemcitabine and docetaxel? What's sort of the current thinking amongst urologists? Dr. Petros Grivas: Multiple factors play into our account when the decision is being made. I discuss with urologists all the time. It's not an easy decision because we do not have head-to-head comparisons between those agents. As you mentioned, intravesical chemotherapy with gemcitabine and docetaxel has been used over the years and this is the lowest cost, I would say, the cheapest option with good efficacy results. Obviously, the nadofaragene firadenovec every 3 months and the interleukin-15 superagonist, N-803, plus BCG have also been approved. The question is availability of those agents, are they available? Are they reimbursed? Cost of those agents can come into play. Frequency of administration, you know, once every 3 months versus more frequent. And of course, the individual efficacy and toxicity data, preference of the patients; sometimes the provider, the urologist, may have something that they may be more familiar with. But we lack this head-to-head comparison. Of course, I want to make sure I mention that radical cystectomy may still be the option for appropriate patients. So that complicates also the decision making and has to be individualized, customized, and personalized, taking into account all those factors. And there is not one size fitting all. Dr. Sumanta (Monty) Pal: So I think we discussed five intravesical therapies. As you point out, and you know, I'm going to get some calls about this: I think I referred to radical cystectomy as being a more primitive procedure. Not true at all. I think it's something that still is, you know, a mainstay of management in this disease space. But I guess it gets even more complicated, am I right, Petros? Because now we have systemic therapies that we can actually apply in this non-muscle invasive setting for at this point, refractory disease. Can you maybe just give us a quick two-minute primer on that? Dr. Petros Grivas: Absolutely, and systemic therapies now come into play, as you said. And a classical example of that, Monty, came from the KEYNOTE-057 trial that we published about 6 years ago. This is intravenous pembrolizumab, given intravascularly, intravenously, as opposed to the previously discussed intravesical administration of agents. Pembrolizumab was tested in that KEYNOTE-057 trial and showed efficacy about, I would say, one out of five patients, about 20%, had a complete response of the tumor in the bladder in a year after starting the treatment. Again, it's hard to compare across different agents, but obviously when we give something intravenously, there is a risk of toxicity, side effects systemically, what we call immune-related adverse events. And this can also play in the decision making, right? When you have intravesical agents versus intravascular agents, there is different toxicity profiles in terms of systemic toxicity. But intravenous pembrolizumab has been an option, FDA approved, since, if I remember, it was early 2020 when this became FDA approved. There are other agents being tested in this disease, but like atezolizumab through the SWOG study that Dr. Black and Dr. Singh led, but atezolizumab is not FDA approved for this indication. Again, this is for BCG unresponsive, high-risk, non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: So maybe teach us how it works, for instance, at an expert center like the Fred Hutch. When you see a patient with non-muscle invasive bladder cancer, there's obviously the option of surgery, there's the intravesical therapies, which I imagine the urology team is still really at the helm of. But then, I guess there has to be consideration of all options. So you've got to bring up systemic therapy with agents like pembrolizumab. In that context, are you involved that early on in the conversation? Dr. Petros Grivas: That's a great discussion, Monty. Paradigm is shifting as we mentioned together. The urologists have been treating these patients and still they are the mainstay of the treaters, the managers in this disease. But medical oncologists come to play more and more, especially with the FDA approval of intravenous pembrolizumab about 5 years ago [GC1]  [KM2] . We have the concept of multidisciplinary bladder cancer clinic here at Fred Hutch and University of Washington. This happens every Tuesday morning, and we're very excited because it's a one-stop shop for the patients. We have the urologist, a medical oncologist, radiation oncologist, and experts from radiology and pathology, and we all review cases specifically with muscle-invasive bladder cancer. But every now and then, we see patients with BCG unresponsive non-muscle invasive bladder cancer. And this is where we discuss and we talk to the patient about pros and cons of all those options. And that's a classic example where medical oncologists may start to see those patients and offer their input and expertise. In addition to that, sometimes we have clinical trials, we may see these patients because there are systemic agents that may be administered in this setting. We have the SunRISe trial program that includes also a systemically administered checkpoint inhibitor. So that's another example where we see patients either in the context of multi-clinic or in individual solo clinics to counsel the patients about the pros and cons of the systemically administered agents in the context of clinical trials. Usually checkpoint inhibitors are the class of agents that are being tested in this particular scenario. Dr. Sumanta (Monty) Pal: I can see a scenario where it's really going to require this sort of deep dive, much in the way that we do for prostate cancer, for instance, where the medical oncologist is involved very early on and planning out any sort of systemic therapy component of treatment or at the very least, at least spelling out those options. I think it's going to be really interesting to see what this space looks like 5 or 10 years down the road. In closing, I wanted to go through something that I think is so different in this space, at least for the time being, and that is the paradigm for FDA approval. When you and I have our fellows in the clinics, we always say, “Look, you know, the paradigm in this disease and that disease and the other disease needs to be phase 3 randomized trials, right? Big thousand patient experiences where you're testing clinical endpoints.” That's tough in non-muscle invasive bladder cancer, right? Because thankfully, outcomes can actually be quite good, you know, in this setting, right? It's tough to actually estimate overall survival in some of these early-stage populations. Tell me what the current regulatory bar is, and this is a tough thing to do in 2 minutes or less but tell me where you see it headed. Dr. Petros Grivas: You alluded to that before, Monty, when I was giving the background and we talked about the regulatory approval. And I have to very quickly go back in time about 10 years ago because it's important for context that can help us in other disease types too. We had workshops with the FDA and the NCI with the help of the International Bladder Cancer Group and other colleagues. And we try to define a framework, what endpoints are meaningful for those patients in this disease. It was a multidisciplinary, multiple stakeholders meeting, where we tried to define what is important for patients. What are the available agents? What are the trial designs we can accept? And what are the meaningful endpoints that the regulatory agencies can accept for regulatory approval? And that was critical in that mission because it allowed us to design clinical trials, for example, single-arm trials in a disease where there was no standard of care. There was intravesical valrubicin and chemotherapy anthracycline that was approved for many years, but was not practically used in clinical practice, despite being approved, the valrubicin. And because of that, the FDA allowed these single-arm trials to happen. And obviously the endpoint was also discussed in that meeting. For example, for carcinoma in situ, complete response, clinical complete response, because the bladder remains intact in many patients, clinical complete response was a meaningful primary endpoint, also duration of response is also very important. So what is the durable clinical complete response in 1 year or 18 months is relevant. And when you have papillary tumors like Ta or T1 with CIS, for papillary tumors, event-free survival becomes one of the key endpoints and you look at it over time, for example, at 12 or 18 months, what is the event-free survival? So clinical complete response, duration of response, event-free survival, depending on the CIS presence or papillary tumors, I think these are endpoints that have allowed us to design those trials, get those agents approved.  Now, the question going forward, Monty, and we can close with that is, since now we have the embarrassment of riches, many more options available compared to where we were 6 and 7 years ago, is now the time to do randomized trials? And if we do randomized trials, which can be the control group? Which of those agents should be allowed to be part of the control group? These are ongoing discussions right now with the NCI, with other agencies, cooperative groups, trying to design those trials and move forward from here.[GC3]  Dr. Sumanta (Monty) Pal: Well, it's awesome to have you here on the program so we can get some early looks into some of these conversations. I mean, clearly, you're at the table at a lot of these discussions, Petros. So I want to thank you for sharing your insights with us today. This was just tremendous. Dr. Petros Grivas: Thank you, Monty. You know, patients in the center, I just came back from the Bladder Cancer Advocacy Network meeting in Washington, D.C., and we discussed all those questions, the topics you very eloquently mentioned and asked me today, and patients gave us great feedback and patients guide us in that effort. Thank you so, so much for having me and congratulations for the amazing podcast you're doing. Dr. Sumanta (Monty) Pal: Oh, cheers, Petros, thanks so much.  And thank you to the listeners who joined us today. If you really like the insights that you heard on this ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. 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.   Find out more about today's speakers:      Dr. Sumanta (Monty) Pal  @montypal  Dr. Petros Grivas @PGrivasMDPhD   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Petros Grivas: Consulting or Advisory Role: Merck, Bristol-Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology, Abbvie, Bicycle Therapeutics Replimune, Daiichi Sankyo, Foundation Medicine, Bicycle Therapeutics, Eli Lilly, Urogen Pharma, Tyra Biosciences Research Funding (Inst.): Bristol-Myers Squibb, Merck, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, ALX Oncology, Genentech Travel, Accommodations, Expenses: Gilead Sciences

Nate and Josh dissect a Reddit post and issue a PSA: Just because you get accommodations on the LSAT and in law school doesn't mean you will get them for the bar exam.Read more on our website. Email daily@lsatdemon.com with questions or comments. Watch this episode on YouTube!

(00:00) Path to Medicine and Representation(10:45) Navigating Challenges in Pre-Med Studies(17:10) Navigating Learning Differences and Accommodations(29:09) Journey to Medical School Acceptance(35:27) Perseverance in the Journey to MedicineAt 17, Katya's life took an unexpected turn when a spark for dermatology lit up her path away from fashion. Join us as Katya shares her unique journey through the world of medicine, a path filled with challenges, self-discovery, and unyielding determination. Hear how her mother's insight into the demand for dermatologists and the experience of shadowing a physician of color solidified her commitment to a field where representation and cultural competence are crucial. Katya's story sheds light on the underrepresentation of Latino physicians in the U.S. and highlights the vital role of family and community support in overcoming self-doubt.The academic journey wasn't smooth sailing for Katya, who faced hurdles at Princeton that tested her resolve. Discover how initial setbacks and lower-than-expected grades fueled her imposter syndrome, propelling her to reevaluate her approach to premed studies. Through strategically pausing her coursework and immersing herself in diverse academic experiences abroad, Katya not only enhanced her college journey but also prepared for future medical school applications. Her candid discussion reveals the power of friendships, therapy, and core values in navigating the demanding world of premed, and serves as a guide for those facing similar battles.Listen as Katya recounts the emotionally charged process of medical school applications, drawing parallels to the unpredictability of dating. From receiving just one interview invite to the thrill of an acceptance call from Stanford on her birthday, her journey is a testament to perseverance against all odds. Katya opens up about learning differences and the significance of accommodations, breaking down the stigma and proving that success is within reach for those who seek the support they need. Her story is a beacon of hope for aspiring medical students, reinforcing that with grit and determination, even the most formidable barriers can be overcome.

Syria: And Israel accommodations. Ahmad Sharawi, FDD https://apnews.com/article/syria-israel-diplomacy-conflict-us-e3fd86d0e2a011e6eba6dea8977bc084

In this episode, Lisa and Zack discuss:Understanding the difference between everyday anxiety and an anxiety disorderThe role of technology and social media in contributing to Gen Z anxietyEvidence-based treatment approaches, including exposure therapyParenting strategies to support anxious teens without reinforcing fearKey Takeaways: Anxiety can be defined as an overestimation of threat and an underestimation of one's ability to cope, and it becomes a disorder when it causes significant dysfunction in daily life.Technology use often serves as a “medication” for uncertainty, providing short-term relief but contributing to worsening anxiety, with research suggesting decreased youth alcohol use but no mental health improvement.Accommodations, such as parents completing tasks for anxious teens, can unintentionally reinforce fears; asking guiding questions helps youth build coping skills.Exposure therapy works by gradually confronting fears until they become manageable or are disproven, reducing avoidance and increasing confidence. “Fear and anxiety have an incredibly important role to play in our lives. It's not all bad. It's not a negative emotion, but it is an emotion that requires some understanding and some skill to address.” – Zack SchaferEpisode References:The Anxious Generation by Jonathan Haidt: https://www.amazon.com/Anxious-Generation-Rewiring-Childhood-Epidemic/dp/0593655036Dopamine Nation by Dr. Anna Lembke: https://www.amazon.com/Dopamine-Nation-Finding-Balance-Indulgence/dp/152474672XSPACE Treatment by Dr. Eli Lebowitz: https://www.spacetreatment.net/BePresent App: https://www.bepresentapp.com/Get Lisa's Free on-demand video: How-to guide for your teen to choose the right major, college, & career...(without painting themselves into a corner, missing crucial deadlines, or risking choices you both regret). flourishcoachingco.com/video Connect with Zack:Instagram: https://www.instagram.com/mountainvalleytreatmentcenter/Website: https://mountainvalleytreatment.org/LinkedIn: https://www.linkedin.com/in/zack-schafer-a6026b108/Fear Less Podcast: https://podcasts.apple.com/us/podcast/Email: zschafer@mountainvalleytreatment.orgConnect with Lisa:Website: https://www.flourishcoachingco.com/YouTube: https://www.youtube.com/@flourishcoachingcoInstagram: https://www.instagram.com/flourishcoachingco/LinkedIn: https://www.linkedin.com/company/flourish-coaching-co

The gap between being "smart" and "struggling" often confuses parents, especially when school accommodations don't seem to be working. Dr. Amy and Sandy dive into this critical topic, exploring how cognitive processing differs from academic learning and why this distinction matters for your child's future.Your child's brain isn't just responsible for thinking and learning—it processes emotions too. When cognitive skills like working memory, processing speed, or reasoning are weak, it affects everything from test performance to social interactions. A child who struggles to process information efficiently experiences frustration that can manifest as behavioral problems, avoidance, or diminished self-confidence. As one parent shared, "My vibrant child began to wilt because he just felt like a failure."The conversation tackles the tough question many parents ask: how far behind is too far behind? While temporary slowdowns in specific subjects aren't concerning, persistent patterns of struggle across multiple areas signal deeper cognitive issues that won't simply resolve with time. These struggles eventually impact self-esteem and emotional well-being, sometimes in ways children can't articulate until they face a significant challenge.Most educational approaches rely heavily on accommodations rather than addressing underlying cognitive weaknesses. While extra time or modified assignments help in the moment, they don't prepare children for college or careers where such accommodations may be limited or unavailable. Building cognitive skills creates long-term solutions that allow children to function independently throughout life.When parents disagree about interventions, the key is moving beyond arguments about the present to discuss fears about the future. What happens if we don't address these issues now? What are the long-term implications for independence and success? By strengthening cognitive skills, we don't change who children are—we free them from unnecessary struggles so their unique gifts can truly shine.CONNECT WITH US: Website: www.TheBrainyMoms.com Email: info@TheBrainyMoms.com Social Media: @TheBrainyMoms Our sponsor's website: www.LearningRx.comSandy's TikTok: @TheBrainTrainerLadyDr. Amy's brand new IG: @DrAmySaysGraceDr. Amy's website: www.AmyMoorePhD.com

For people with Multiple Chemical Sensitivity (MCS), this is often our reality: We're told the illness isn't real — it's just in our heads — and the law refuses to protect us.In this episode of The Chemical Sensitivity Podcast, Professor Doron Dorfman, a disability law scholar at Seton Hall University School of Law in Newark, New Jersey, in the U.S., explores how:People with Multiple Chemical Sensitivity (MCS) face discrimination because courts often dismiss fragrance-free policies as unreasonable.No-smoking rules and peanut-free zones could serve as examples for fragrance-free policies.Fragrance-free policies are truly not an administrative burden, as some argue.And more! I'd love your help. I'm running a short listener survey to understand how The Chemical Sensitivity Podcast can best serve people with MCS. It's short, will help guide our next steps, and allow us to grow the podcast and create greater awareness about MCS. Thank you for your support! Please find the link here:https://docs.google.com/.../1FAIpQLSeVqlO2G5OMxN.../viewformAaron.#MultipleChemicalSensitivity #MCS #ChemicalIntolerance #EnvironmentalIllness #ChemicalSensitivityPodcast #DisabilityRights #FragranceFree #AccessibilityMatters #EnvironmentalJusticeSupport the showThank you very much to the Marilyn Brachman Hoffman Foundation for its generous support of the podcast.If you like the podcast, please consider becoming a supporter! Support the podcast. Find the podcast on Patreon. If you like, please buy me a coffee. Follow the podcast on YouTube! Read captions in any language. Please follow the podcast on social media:FacebookInstagramBlueSkyTikTokSponsorship Opportunites Are you an organization or company interested in helping to create greater awareness about Multiple Chemical Sensitivity and Chemical Intolerance and/or looking for sponsorship opportunities? Please email us at info@chemicalsensitivitypodcast.org

#thePOZcast is proudly brought to you by Fountain - the leading enterprise platform for workforce management. Our platform enables companies to support their frontline workers from job application to departure. Fountain elevates the hiring, management, and retention of frontline workers at scale.To learn more, please visit: https://www.fountain.com/?utm_source=shrm-2024&utm_medium=event&utm_campaign=shrm-2024-podcast-adam-posner.Thanks for listening, and please follow us on Insta @NHPTalent and www.youtube.com/thePOZcastFor all episodes, please check out www.thePOZcast.com  SummaryIn this episode, Adam Posner interviews Charlotte Dales, co-founder and CEO of Inclusively, a platform dedicated to creating equitable workplaces. Charlotte shares her journey from finance to founding Inclusively, inspired by her cousin Cameron's achievements despite challenges. The conversation delves into the importance of workplace accommodations, the role of anonymity in fostering inclusion, and the need for data-driven insights to bridge gaps in employee support. Charlotte discusses the pivot from a hiring platform to a focus on retention and the future of work, emphasizing skills-based hiring and authentic DEI practices. She also offers advice for aspiring founders on balancing personal and professional life while defining success beyond financial metrics.Takeaways: - Inclusively aims to create equitable workplaces through technology.- Charlotte's inspiration came from her cousin Cameron's journey.- Accommodations in the workplace can significantly impact employee success.- Anonymity in requesting support is crucial for employee comfort.- Data-driven insights help align employee needs with company offerings.- The business model pivoted from hiring to retaining talent.- Skills-based hiring complements the need for accommodations.- Authenticity in DEI practices is essential for real impact.- Balancing work and personal life can enhance productivity.- Success is defined by the positive impact on future generations.Chapters00:00 Introduction to Inclusively and Its Mission02:59 Charlotte's Journey: From Finance to Founding Inclusively06:03 Inspiration from Family: Cameron's Story08:55 The Importance of Accommodations in the Workplace11:51 The Role of Anonymity in Workplace Inclusion14:47 Bridging the Gap: Data-Driven Insights for Employers17:57 Pivoting the Business Model: From Hiring to Retaining Talent20:54 The Future of Work: Skills-Based Hiring and Inclusion24:00 Navigating the DEI Landscape: Authenticity vs. Performative Actions26:58 Advice for Aspiring Founders: Balancing Life and Work29:42 Defining Success: Beyond Numbers and Exits 

Interviewees: Emily Green, MD and Kelley Volpe, MD Interviewer: Lisa Meeks, PhD, MA Description: In Episode 113, Dr. Lisa Meeks talks with Dr. Emily Green (child psychiatrist, University of Chicago; recent fellow at UIC) and Dr. Kelley Volpe (training director of the Child and Adolescent Psychiatry Fellowship at UIC) about navigating fellowship with ADHD and a learning disability—and how openness, advocacy, and leadership support shaped a successful training experience. Together, they trace Emily's decision-making during the match, the challenges of transitioning from residency to fellowship (and from student to employee), and the unexpected barriers in GME accommodation processes. They unpack how program leadership stepped in when paperwork stalled, why “temporary vs. chronic” misunderstandings of disability remain a problem, and how centering inclusion ultimately benefited both the trainee and the program. Listeners will hear advice for residents and fellows (be specific in accommodation requests, know when disclosure matters, embrace authenticity with patients) and for program directors (be proactive with GME, advocate beyond bureaucracy, and create space for trainees to bring their whole selves to medicine). This episode accompanies the open-access case study From Policy to Practice: Building the Disability Inclusion Infrastructure in Graduate Medical Education (Green & Volpe, Academic Medicine, 2025). Part of the ACGME/DWDI Disability Resource Hub, supported by the Josiah Macy Jr. Foundation Catalyst Award, it's both a roadmap and a reminder that when programs invest in access, everyone wins. Transcript: https://docs.google.com/document/d/1uhs1zRh2QOWVMgYlEFkxbFY-MJQbiqV_/edit?usp=sharing&ouid=104315301750264632478&rtpof=true&sd=true Bios:  Kelly Volpe, MD Dr. Kelley Volpe is the medical director of the Pediatric Stress & Anxiety Disorders Clinic at UI Health. Dr. Volpe currently provides outpatient services that are specialized in the treatment of anxiety disorders, such as generalized anxiety, social anxiety, obsessive compulsive disorder, and selective mutism, in addition to trauma- and stress-related disorders. She is board certified in both General Psychiatry and Child & Adolescent Psychiatry. Emily Green, MD Emily is an Assistant Professor of Psychiatry and Behavioral Neuroscience at the University of Chicago. She specializes in pediatric psychiatry and helps children and adolescents who are struggling with mental well-being. Key Words:   Disability Inclusion Residency Fellowship ADHD Learning Disability Psychiatry Accommodations Program Directors Graduate Medical Education (GME) Produced by: Lisa Meeks  Resources:  Disability Resource Hub: https://dl.acgme.org/pages/disability-resource-hub Case Studies in Disability Resource Hub: https://dl.acgme.org/pages/disability-resource-hub#case_studies UME to GME Toolkit:  https://dl.acgme.org/pages/disability-resource-hub-transitions-toolkit-introduction Policy Toolkit:  https://dl.acgme.org/pages/disability-resource-hub-policy-toolkit Disability in Graduate Medical Education Program:  https://www.docswithdisabilities.org/digme Illinois Lend: https://www.illinoislend.org Case Study: From Policy to Practice: Building the Disability Inclusion Infrastructure in Graduate Medical Education      

Interviewees: Josh Schammel, MD; Brian Inouye, MD; and Becky Stetzer, MD Interviewer: Justin Bullock, MD, MPH Description: In this episode, Dr. Justin Bullock talks with Dr. Josh Schammel (chief urology resident at Albany Medical Center), Dr. Brian Inouye (associate program director of urology at Albany Med), and Dr. Becky Stetzer (assistant dean of competency development, Albany Med) about navigating remediation, cognitive disability support, and institutional change in residency training. Together, they trace Josh's experience entering urology residency off-cycle, the social and educational challenges that followed, and the turning point that came with honest conversations about expectations and support. They explore how leadership reframed remediation from punitive to restorative, how program culture embraced accommodations even without a formal diagnosis, and how outside expertise in competency development reshaped both Josh's trajectory and the program's systems. Listeners will hear candid reflections on the fear of dismissal, the relief of being given a “do-over” year, and the powerful role of trust and transparency in rebuilding confidence. The team highlights the importance of creating a culture where struggling is not synonymous with failure, but with an opportunity for growth. This episode accompanies the open-access article A Master Adaptive Learner Approach to Cognitive Disability Support in a U.S. Urology Residency (Stetzer et al., Teaching and Learning in Medicine). Part of the ACGME/DWDI Disability Resource Hub, supported by the Josiah Macy Jr. Foundation Catalyst Award, it's a practical and deeply human guide for residents, faculty, and program leaders working to build equitable clinical learning environments. Transcript: https://docs.google.com/document/d/1u-qRRgjrB-lOJnQytGy7C7ByxYppdfju/edit?usp=sharing&ouid=104315301750264632478&rtpof=true&sd=true Key words: Medical education, cognitive disability, residency, accommodations, program director, GME, GME Policy, Disability, Training, PTSD. Bios:   Resources:  Disability Resource Hub: https://dl.acgme.org/pages/disability-resource-hub Case Studies in Disability Resource Hub: https://dl.acgme.org/pages/disability-resource-hub#case_studies UME to GME Toolkit:  https://dl.acgme.org/pages/disability-resource-hub-transitions-toolkit-introduction Policy Toolkit:  https://dl.acgme.org/pages/disability-resource-hub-policy-toolkit Disability in Graduate Medical Education Program:  https://www.docswithdisabilities.org/digme Link to Case Study: A Master Adaptive Learner Approach to Cognitive Disability Support in a U.S. Urology Residency https://www.tandfonline.com/doi/10.1080/10401334.2025.2502670?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed  

Dr. Sumanta (Monty) Pal and Dr. Arielle Elkrief discuss the clinical relevance of the gut microbiome in cancer immunotherapy and the importance of antibiotic stewardship, as well as interventions currently being explored to treat gut dysbiosis and optimize immunotherapy response. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hi everyone, I'm Dr. Monty Pal, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist. I'm a professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles.  Today we're here to discuss one of my favorite topics, which is the gut microbiome. It's almost hard to avoid the gut microbiome nowadays if you look at medical literature within oncology. It's an emerging phenomenon, but there are a couple of individuals that I would really define as pioneers in the field. And one of them is actually with me today, Dr. Arielle Elkrief, to discuss the clinical relevance of the gut microbiome, particularly amongst patients receiving immunotherapy, although I imagine our conversation today will take many twists and turns. Arielle is an assistant professor and clinician scientist in the Department of Oncology at the University of Montreal, and she is co-director of the CHUM Microbiome Center there.  FYI for the listeners, we have our full disclosures in the transcript of this episode.  Arielle, thank you so much for joining us today. Dr. Arielle Elkrief: Thanks so much, Monty. This is going to be amazing. Dr. Sumanta (Monty) Pal: Well, I have to tell you what sort of inspired me to bring you on as a guest. It was one of many things, but it was this really terrific ASCO Educational [Book] article that you wrote. Now, I have to tell you, I've read all the articles sort of cover to cover in the book, and they're always a wonderful primer, so if our audience is studying for board research or something of that sort, it's a terrific resource to go through. I have to tell you, this piece on the gut microbiome that you wrote is nothing short of a masterpiece. If you read this cover to cover, it's actually going to give you, I think, a sense of the current state and future state of the field. I wanted to start by just sort of beginning with sort of the origin story for a lot of this, which is this association between the gut microbiome and immunotherapy response. This takes us back several years to this pivotal series of papers in Science. Maybe you could walk our audience through that. Dr. Arielle Elkrief: Absolutely. Well, thank you so much for your kind words about the ASCO [Educational] Book. It was a team effort with a lot of key opinion leaders in the field, so I'm really glad to learn that you've liked it.  Moving backwards in terms of how we came to understand that the gut microbiome is essential to priming a response to cancer immunotherapy actually goes back to 2015 and seminal papers that looked at what happens when we take mice that are germ-free mice that have never been exposed to a microbiome. These are mice that are born by cesarean section and essentially live in a bubble. And when we give those mice tumors and treat them, in the first papers with anti-CTLA-4 treatment, we realized that these antibodies don't work at all. And that was the first observation that the presence of a gut microbiome was essential to mounting an anti-cancer immune response. When we supplemented those same mice with beneficial bacteria or feces from responder patients, we were able to restore the response to immunotherapy. And so those were really the first preclinical observations that made us understand the critical role of the microbiome in immunotherapy response. Moving a little bit in the future, we examined the fecal microbiome composition using shotgun metagenomic sequencing in different cohorts of patients with solid tumors, namely lung cancers, kidney cancers, and also skin tumors like melanoma, and found that patients who responded to immunotherapy had a distinct microbiome that was characterized by beneficial bacteria compared to patients who experienced resistance to immunotherapy that had a dysbiotic or diseased microbiome. Dr. Sumanta (Monty) Pal: So, you know, it's interesting, these techniques that we're using to sequence the gut, they're a little bit different. So I wonder if you can give the audience a quick primer on these techniques that you're so well versed in, shotgun metagenomic sequencing, 16S rRNA sequencing. If you had to describe this in 30 seconds, which is a tall task, how would you do that? Dr. Arielle Elkrief: That's a tall task. Much of what we know about the microbiome initially came from a technique called 16S rRNA sequencing. This is a technique that amplifies the 16S region and basically tells you at the genus level what's going on at the level of bacterial composition. This technique is fast, relatively cheap, and can be performed on a laptop computer, which is excellent. The problem is that it's prone to a lot of technical variations. Different primers might give you different results, and you're really limited at the genus resolution. You can't get a good resolution in terms of species, and we're learning that different species from the same genus might have different physiological properties, and the same thing goes at the strain level. So when we really zone in and look at inter-species changes, we're seeing that these actually have specific functions in the host. So that brings us to metagenomic sequencing, which is a whole genome sequencing, next-generation sequencing based method that looks at the whole composition and gives you information not only on bacteria, but you might also get fungal and viral properties. You can zoom in on the strain level. You can also get functional output, so we can examine what the metabolic properties of specific species or strains might look like. The negative aspects of shotgun metagenomic sequencing is that it takes a lot of computational power in order to analyze the results and it might take a little bit longer. And certainly, within the clinical setting, not something that's feasible yet.  And that brings us to more novel point-of-care biomarker tools that we've collaborated in developing along with Dr. Laurence Zitvogel and Dr. Lisa Derosa at Gustave Roussy, that learning from the shotgun metagenomics results designed a probe using quantitative PCR which looks for this specific bacteria we know to be important and developed a ratio of harmful bacteria to beneficial bacteria. This is called the TOPOSCORE, and it actually is able to predict quite nicely the response to immunotherapy using a stool sample and a really good turnaround time of almost 72 hours. Dr. Sumanta (Monty) Pal: That was a perfect overview and a lot of information in a short amount of time. It also makes you take out your high school biology textbooks, doesn't it, to understand that the bacterial ribosome, right, is a different size and shape, and that's what we're sequencing here. But these techniques I think are incredibly important, and I'm glad you actually discussed this, this RT-PCR based strategy of calculating the TOPOSCORE. It lends itself to this phenomenon of dysbiosis, and I think for our audience, that's going to be an important term to understand as time goes on. There's the normal healthy gut and then there's this phenomenon of dysbiosis, which is, I guess, simply put, an unhealthy gut. But tell us about, you know, how often you see dysbiosis in a cancer patient, maybe versus a normal healthy adult. Dr. Arielle Elkrief: So, I think we can split up your question into two parts. One is we know from cohort studies and population level-based studies that the microbiome of patients with cancer is distinct from healthy patients or healthy people. And we know that because of the global composition. We also think that there are diversity metrics that lend themselves to being described as dysbiotic. But we do know that the microbiome of people with cancer is distinct from healthy volunteers. That's the first point.  In terms of how frequently dysbiosis occurs in patients with cancer, it's not very well defined. We know that even among healthy people, there is a certain level of dysbiosis. Laurence in her talk mentioned that to be about 10% to 20%. And the other fascinating component is that when we're thinking about dysbiosis and the cancer associated microbiome, in terms of the species that are enriched, it's quite striking that a lot of these dysbiotic or negative bacteria are also found to be enriched in patients with metabolic disease, like cardiovascular disease, for example. And so it's unclear if dysbiosis is the cause or consequence, but there definitely seems to be a general pattern of disease when looking at the microbiome compared to healthy people. Dr. Sumanta (Monty) Pal: That's interesting. So, I'll tell you, my second favorite portion of your article, and I'll tell you my favorite portion as well in the context of this podcast, but my second favorite part was the section around antibiotic stewardship. You know, the utilization of antibiotics in a very pragmatic fashion amongst our patients. Can you describe why that's so critical in the context of the microbiome? Dr. Arielle Elkrief: Antibiotics can disrupt the gut microbiome composition. We know this from mouse studies, but also cohort studies of patients that are exposed to antibiotics. And most importantly, we know that patients who are exposed to antibiotics, either before or during the immunotherapy period, have significantly worse progression-free survival and overall survival to immunotherapy. And this is true for immunotherapy in the monotherapy setting, but also when combined with chemotherapy. What's striking is that when we look at patients who are just treated with chemotherapy, we don't see the negative outcome of antibiotics on outcome and progression-free survival and overall survival, suggesting that the negative impact of antibiotics on outcomes is really specific to immunotherapy backbones. The other important point is that this negative signal is maintained even after adjusting for standard prognostic variables in the specific malignancies that we're looking at. And then most importantly, at the mechanistic level, we were able to actually pinpoint the mechanism behind this antibiotic related dysbiosis. And we see this with a bloom of negative bacteria which induces a loss of MAd-CAM, which is an endothelial gut checkpoint immune marker, and that causes an efflux of immunosuppressive T cells, which are usually in the gut, to go straight into the tumor where they make the tumor unamenable to an immunotherapy response. And so now we finally have the mechanism as to why antibiotics are harmful and why we need to practice antibiotic stewardship. Dr. Sumanta (Monty) Pal: And just to be clear for the audience, I mean, if a patient needs antibiotics, they need antibiotics. But perhaps it just suggests that, and we have, I suppose, this predilection as oncologists, just for the minor cold or cough or what have you, we maybe should be a little bit more cognizant of whether or not antibiotics are truly necessary. Is that fair? Dr. Arielle Elkrief: Absolutely. So what we're advocating for is antibiotic stewardship, and this is the clear recommendation that we can make. So that means confirming a bacterial infection. If it's there and antibiotics are indicated, to choose the most narrow spectrum for the shortest course and constantly re-evaluate the indication of antibiotics. And of course, we need to work with our colleagues in infectious diseases who've done incredible work in antibiotic stewardship. And all along this process we also need to be mindful of other medications and polypharmacy, such as proton pump inhibitors or narcotics, for example, we think that these other medications which are frequently prescribed in our cancer population can also potentially have negative impacts on the microbiome and immunotherapy response. Dr. Sumanta (Monty) Pal: I think that's a terrific summary and big guidance for the audience.  I promised you I'd tell you my favorite part of your article, and this is this huge table. I think the table is two and a half pages long, if I remember correctly, but it's an awesome table, and I highly recommend our audience to check this out. It lists literally every therapeutic trial for the microbiome under the sun. And so it begins with the approach of fecal microbiota transplant, which I'm going to ask you to tell us about in a second, but it also hinges on a lot of really cool sort of novel therapies, live bacterial products, mixes of different microbial products. Maybe take us through this whole approach of FMT (fecal microbiota transplantation). I actually wasn't aware of the dozens of trials that you listed there in this space. It seems like it's a very active area of research. Dr. Arielle Elkrief: Definitely. So, as you alluded to, FMT or fecal microbiota transplantation is the most well studied and direct way to modify the patient's microbiome. This technique aims to replace the patient's dysbiotic microbiome with that of a healthy microbiome, either from a healthy donor volunteer that's been heavily screened, or from a patient who experienced response to immunotherapy. And, as three landmark studies so far that have been published demonstrated the potential of FMT to reduce primary resistance or secondary resistance to immunotherapy, and this has been in melanoma.  We also recently reported on the results of our FMT-LUMINate trial, which looked at patients with lung cancer and melanoma. Once again, FMT, when combined with immunotherapy was safe and led to a higher proportion of responses than we would normally expect.  We're now also looking at randomized trials that have come out. So the first being the TACITO trial in kidney cancer, which compared FMT plus pembrolizumab and axitinib to placebo in patients with RCC, and again, FMT was safe and feasible and also led to an increased progression-free survival at one year, meeting the study's primary endpoint.  And so, so far, there's a wealth of data really showing the promise of FMT when combined with immunotherapy, and we're now in the process of conducting larger randomized trials, including in melanoma with the CCTG (Canada Cancer Trials Group) in our ME17 or Canbiome2 trial, where we're going to be enrolling 128 patients with metastatic melanoma to receive FMT and standard of care immunotherapy compared to standard of care immunotherapy alone. Dr. Sumanta (Monty) Pal: You're very humble, so I've got to highlight for our audience. This was a mega grant that Arielle received to fund really the largest prospective exploration of FMT that will exist to date. So I'm really excited about that. I wish this was something we could participate in stateside.  Before we jump into the other approach, which is live bacterial products and mixes thereof, where do you see FMT going? I think that one of the perceived challenges with FMT is that it's hard to implement, right? You need to have a really robust framework when it comes to gastroenterology, the preparation's challenging. Is there a way to envision FMT use being more generalized? Dr. Arielle Elkrief: Those are great questions. So we're lucky in Canada to work with pioneers in FMT, Michael Silverman, Saman Maleki, and John Lenehan in London, Ontario, who had this really robust FMT healthy donor screening program, which literally screens for every pathogen under the sun, and we haven't had any problems with feasibility or implementing FMT in Canada. But I think that once we're going to hopefully start doing larger scale, randomized phase three studies, that we might run into problems with scalability. And I think also with regards to reproducibility, and that's the feedback that we're getting from some regulatory authorities, especially at the level of the FDA, where there are some concerns around inter- and intra-donor variability because, of course, we can't guarantee that every fecal sample is going to be the same. So that has really pushed the field to think about other strategies, such as live biotherapeutic products which take modified FMT or bacteria from stools from either healthy donors or from responder patients and basically turn them into drugs that are regulated as drugs and can then be studied in the context of investigational new drugs or products. Dr. Sumanta (Monty) Pal: I like this and, you know, I do think that there's a future for it. We just have to kind of put our heads together and figure out how to get over all of these logistical hurdles, but, you know, I agree, I think your group and others have demonstrated, especially with this trial that you're fanning out all throughout Canada, that it can potentially be done.  This is a topic that could probably go on for another couple of hours, right, especially based on the size of the table that you put together in this brilliant article, but tell us about live bacterial products or LBPs, as we call them these days. What's the current status, what's the future there? And maybe I'll give you less than two minutes here, although again, I realize it's a two-hour topic. Dr. Arielle Elkrief: You're probably better suited to speak about that because you've been one of the pioneers in terms of this. So we can think about LBPs in terms of single strain organisms, like CBM588 for an example, which your group did some amazing work in showing that, in a randomized setting, that this led to better responses than we would expect compared to just work with controls. We also know that LBPs can have multiple strains, up to 30. We're collaborating with a company called Cannabis Bioscience that is actually working on much larger communities of consortia. And so we're really excited about the direction that that's taking in terms of taking these LBPs and developing them from the drug perspective. In addition to LBPs, we know that there are other ways that we can change the microbiome, notably prebiotics, which are compounds which can have a beneficial impact on the microbiome. And one of these is camu camu, which I know your group is leading a clinical trial looking at camu camu and kidney cancer, and we're excited to see how that compares to FMT or LBPs, because that might be a potentially scalable alternative. Dr. Sumanta (Monty) Pal: That's awesome. What a terrific overview, and that was less than two minutes. I don't know how you did it. That's terrific.  Arielle, this has been such an insightful conversation. I just want to thank you for, again, a terrific article in the ASCO Educational Book. I highly recommend all of our listeners to go there and check it out, and also for sharing all these terrific insights on the podcast today. Dr. Arielle Elkrief: Thank you so much, Monty. Dr. Sumanta (Monty) Pal: And thanks to our listeners, too. If you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. 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. Find out more about today's speakers:    Dr. Sumanta (Monty) Pal  @montypal Dr. Arielle Elkrief Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Arielle Elkrief: Honoraria: AstraZenica, Bristol-Myers Squibb, Merck, EMD Serono Consulting or Advisory Role: Bristol-Myers Squibb Research Funding (Inst.): Kanvas Bioscience, AstraZeneca, Merck Other Relationship: Royal College of Surgeons and Physicians of Canada, Cedar's Cancer Center (Henry R. Shibata Fellowship), Canadian Institutes of Health Research (CIHR)

Does this sound familiar? You keep hearing that the only way to thrive as a highly sensitive or neurodivergent leader is to just “toughen up” and push through—so you try to fit into that mold, but end up feeling exhausted, misunderstood, and on the edge of burnout. It's frustrating, right? You're told your sensitivity holds you back, but all that's doing is making you question your worth and lose touch with your real strengths. What if embracing your unique wiring is actually the secret to authentic, impactful leadership (and way less burnout)? In this episode, you will be able to: Discover strategies that turn high sensitivity into a leadership superpower for more authentic and effective influence. Unlock the unique advantages neurodivergent leaders bring that boost innovation and team success in unexpected ways. Learn how to recognize early signs and create habits that prevent burnout before it takes hold in neurodivergent professionals. Embrace neurodiversity to build a workplace culture that values different minds and drives inclusive collaboration. Harness the power of empathy to transform leadership style and deepen connections that inspire lasting team loyalty. My special guest is Rachel Radway Rachel Radway is a certified leadership coach, mentor, speaker, and author with 25+ years' experience in corporate leadership roles in startups, national nonprofits, and global enterprises. Rachel helps high-achieving, highly perceptive and neurodivergent clients learn to lead with confidence, clarity and authenticity—and without burning out. Her book, Perceptive, has received endorsements and rave reviews from leaders from diverse backgrounds across industries. The key moments in this episode are:00:01:13 - Rachel Radway's Background and Purpose of Her Book "Perceptive" 00:07:33 - The Meaning Behind the Book Title "Perceptive" and Reframing Sensitivity 00:11:34 - Recognizing High Sensitivity and Neurodivergence in Yourself and Others 00:14:41 - Understanding High Sensitivity and Neurodivergence 00:17:00 - Navigating Disclosure and Accommodations in the Workplace 00:20:31 - Leveraging Neurodivergent Strengths in Leadership and Teams 00:24:00 - Creativity, Pattern Recognition, and Inclusion in the Workforce 00:27:05 - The Impact of Global Culture on Sensitivity and Inclusion 00:29:07 - Understanding Empathy and Cultural Sensitivity in Leadership 00:31:35 - The Challenges of Burnout for Highly Sensitive and Neurodivergent Leaders 00:37:26 - Strategies to Prevent Burnout in Neurodivergent and Highly Sensitive Individuals 00:40:47 - Embracing Neurodiversity and Cognitive Diversity in the Workplace 00:42:13 - Leveraging Perceptiveness as a Leadership Superpower 00:43:06 - Unlocking Blue Ocean Strategies Through Perceptive Leadership 00:44:04 - Exclusive Insights: Leaders Unlocking Perceptive Superpowers 00:44:48 - Amplifying Impact: Sharing and Supporting Leadership Growth Listen to the episode featuring Minette Norman to learn more about inclusion at work and psychological safety. Take the online high sensitivity assessment at sensitivityresearch.com to determine if you are highly sensitive. Purchase and read Rachel Radway's book, Perceptive, for insights on turning sensitivity into a leadership advantage. Access the exclusive Patreon interview for additional behind-the-scenes content with Rachel Radway.Subscribe to the podcast, leave a review, and share this episode with someone who might need to hear it. Your support helps the community grow and keeps these important conversations going. If you need professional help, such as therapy: https://www.betterhelp.com/difference If you are looking for your next opportunity, sign up for Lori's Masterclass on Master the Career Pivot: https://www.loriadamsbrown.com/careerpivot Difference Makers who are podcast listeners get 10% offf with the code: DIFFERENT Learn more about your ad choices. Visit megaphone.fm/adchoices

JCO PO author Dr. Alison M. Schram at Memorial Sloan Kettering Cancer Center shares insights into her JCO PO article, “Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors.” Host Dr. Rafeh Naqash and Dr. Schram discuss relevant genomic and clinical features of patients with BRCA-altered uterine sarcoma and the efficacy of PARPis in this population. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and associate professor at the OU Health Stephenson Cancer Center. Today, we are excited to be joined by Dr. Alison Schram, Associate Attending Physician and Section Head of Oral Therapeutics with Early Drug Development and Gynecologic Medical Oncology Services at the Memorial Sloan Kettering Cancer Center, and the senior author of the JCO Precision Oncology article titled, "Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors." At the time of this recording, our guest's disclosures will be linked in the transcript. Dr. Schram, thank you for joining us today. I am excited to be discussing this very interesting, unique topic based on what you published in JCO PO. Dr. Alison Schram: Thank you for having me. Dr. Rafeh Naqash: What we like to do for these podcasts is try to make them scientifically interesting but at the same time, keep them at a level where our trainees and other community oncology professionals understand the implications of what you've published. So I'd like to start by asking you, what is leiomyosarcoma for those of us who don't necessarily know a lot about leiomyosarcoma, and what are some of the treatment options for these uterine sarcomas? Dr. Alison Schram: Uterine leiomyosarcoma is a rare subtype of uterine cancer, and it represents about 1% of all female cancers in the reproductive tract. This is a rare malignancy that arises from the myometrial lining of the uterus, and it is generally pretty aggressive. In terms of the standard therapy, the standard therapy for uterine leiomyosarcoma includes chemotherapy, generally combination chemotherapy, but despite a few regimens that tend to be effective, the duration of effectiveness is relatively short-lived, and patients with advanced uterine leiomyosarcoma eventually progress and require additional therapy. I will say that localized uterine leiomyosarcoma can be treated with surgery as well. Dr. Rafeh Naqash: Thank you for that description. Now, there are two aspects to what you published. One is the sarcoma aspect, the leiomyosarcoma, and the second is the BRCA mutation. Since we are a precision medicine journal, although we've discussed BRCA a couple of times before, but again, for the sake of our listeners, could you highlight some of the aspects of BRCA and PARP sensitivity for us? Dr. Alison Schram: Yes. So BRCA is a gene that's important for DNA repair, and BRCA mutations can be either inherited as a germline mutation, so one of your parents likely had a BRCA mutation and you inherited one copy. In patients who have an inherited BRCA mutation, the normal cells tend to have one abnormal copy of BRCA, but if a second copy in the cell becomes altered, then that develops into cancer. And so these patients are at increased risk of developing cancers. Specifically, they are at an increased risk of developing ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, and a few others. These cancers are considered BRCA-associated tumors. Alternatively, some patients, more rarely, can develop BRCA-altered cancers completely sporadically. So it's a mutation that happens in the tumor itself, and that can lead to impaired DNA repair and promote cancer progression. And those patients are not, they don't have any inherited risk, but just a random event caused a BRCA mutation in the tumor. The reason this is important is because, in addition to it being potentially important for family members, there are certain treatments that are more effective in BRCA-altered cancers. And the main example is PARP inhibitors, which are small molecule inhibitors that inhibit the PARP enzyme, and there is what we call synthetic lethality. So PARP is important for DNA repair, for single-stranded DNA repair, BRCA is important for double-stranded DNA repair, and in a patient that has a cancer that has a BRCA mutation, that cancer becomes more reliant on single-stranded DNA repair. And if you inhibit it with a PARP inhibitor, the cancer cells are unable to repair DNA, and the cells die. So we call that synthetic lethality. PARP inhibitors are FDA approved in several diseases, predominantly the BRCA-associated diseases I mentioned: breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. Dr. Rafeh Naqash: That was very beautifully explained. Honestly, I've heard many people explain BRCA before, but you kind of put it in a very simple, easy to understand format. You mentioned this earlier describing germline or hereditary BRCA and somatic BRCA. And from what I gather, you had a predominant population of somatic BRCA, but a couple of germline BRCA as well in your patient population, which we'll go into details as we understand the study. You mentioned the second hit on the germline BRCA that is required for the other copy of the gene to be altered. In your clinical experience, have you seen outside of the study that you published, a difference in the sensitivity of PARP for germline BRCA versus a somatic BRCA that has loss of both alleles? Dr. Alison Schram: So we will get into what's unique about uterine sarcomas in just a minute. In uterine sarcomas, what we have found is that the BRCA mutations tend to be somatic and not germline, as you mentioned. That is in contrast to the other diseases we mentioned, where the vast majority of these tumors are in patients that have germline BRCA alterations. So one thing that's really unique about the uterine sarcoma population and our paper, I believe, is that it is demonstrating an indication for PARP inhibitors in a population that is not characterized by germline BRCA alterations, but truly these by somatic BRCA alterations. If you look at the diseases that PARP inhibitors are validated to be effective in, including the, you know, the ones I mentioned, the BRCA-associated tumors, there's some data in specific context that suggests that perhaps germline alterations are more sensitive to PARP inhibitors, but that's not universal, and it's really tricky to do because the genetic testing that we have doesn't always tell you if you have two hits or just one hit. So you need more complex genetic analysis to truly understand if there is what we call a biallelic loss. And sometimes it's not a second mutation in BRCA. Sometimes it's silencing of the gene by hypermethylation or epigenetics. Some of our clinical trials are now incorporating this data collection to really understand if biallelic loss that we can identify on more complex genetic testing predicts for better outcomes. And we think it's probably true that the patients that have biallelic loss, whether it be germline or somatic biallelic loss, are more likely to benefit from these treatments. That still needs to be tested in a larger cohort of patients prospectively. Dr. Rafeh Naqash: In your clinical experience, I know you predominantly use MSK-IMPACT, but maybe you've perhaps used some other NGS platforms, next-generation sequencing platforms. Have you noticed that these reports for BRCA alterations the report mentioning biallelic loss in certain cases? I personally don't- I do lung cancer, I do early-phase lung cancer as well, but I personally don't actually remember if I've seen a report that actually says biallelic loss. So after this podcast, I'm going to check some of those NGS reports and make sure I look at it. But have you seen it, or what would be a learning point for the listeners there? Dr. Alison Schram: Exactly. And they usually do not. They usually do not explicitly say, “This looks like biallelic loss,” on the reports. The exception would be if there's a deep deletion, then that implies both copies of the gene have been deleted, and so then you can assume that it's a biallelic loss. But oftentimes, when you see a frameshift alteration or a mutation, you don't know whether or not it's a biallelic loss. And you may be able to get some clues based on the variant allele frequencies, but due to things like whole genome duplication or more complex tumor genomics, it's not clear from these reports, and you really do need a more in-depth bioinformatic analysis to understand whether these are biallelic or not. So that is why I suggest that this really needs to be done in the context of a clinical trial, but there is definitely a theoretical rationale for reporting and treating patients with biallelic losses perhaps more so than someone who has a variant of unknown significance that seems to be monoallelic. The other tricky part, as I mentioned, is the fact that there could be epigenetic changes that silence the second copy, so that wouldn't be necessarily evident on a DNA report, and you would need more complex molecular testing to understand that as well. Dr. Rafeh Naqash: Sure. Now, going to your study, could you tell us what prompted the study, what was the patient population that you collected, and how did you go about this research study design? Dr. Alison Schram: It's actually a great story. I was the principal investigator for a clinical trial enrolling patients regardless of their tumor type to a combination of a PARP inhibitor and immunotherapy. And this was a large clinical trial that was being done as a basket study, as I mentioned, for patients that have either germline or somatic alterations with advanced solid tumors that had progressed on standard therapy. And the hypothesis was that the combination of a PARP inhibitor and immunotherapy would be synergistic and that there would be increased efficacy compared to either agent alone and that patients who had BRCA alterations were a sensitive population to test because of their inherent sensitivity to PARP inhibitors and perhaps their increased neoantigen burden from having loss of DNA repair. So this large study, it's been published, really did show that there was efficacy across several tumor types, but it didn't seem to clearly demonstrate synergy between the immunotherapy and the PARP inhibitor as compared to what you might expect from a PARP inhibitor alone, and in addition to a couple of cases, perhaps attributable to the immunotherapy. So maybe additive rather than synergistic efficacy. However, what really struck me looking at the data was that there were three patients with uterine leiomyosarcoma with BRCA deletions who had the best responses of anyone on the study. So incredible, durable responses. One of my patients with a complete response that continues to not have any evidence of cancer eight years after the initiation of this regimen. And for those of us that treat uterine leiomyosarcoma, this is unheard of. These patients generally, as I mentioned, respond, if they do respond to chemotherapy, it's generally short-lived and the cancer progresses. And so a complete response nearly a decade later turns heads in this field. The other interesting thing was that these uterine leiomyosarcoma patients had somatic alterations rather than a germline alteration with a second hit, and the diseases that are best validated for being responsive to PARP inhibitors include the BRCA-associated diseases, the ones that you're at increased risk for if you have a germline BRCA mutation, including breast, pancreas, prostate, and ovarian. And so it was very interesting that this disease type that seemed to be uniquely sensitive to PARP inhibitors with immunotherapy was also different in that patients with uterine leiomyosarcoma don't tend to have a high frequency of BRCA alterations, and in patients that are born with a BRCA alteration, there doesn't seem to be a clearly increased risk of uterine sarcomas. So this population really jumped out as a uniquely sensitive population that differed from the prior indications for PARP inhibitors. Given this patient and these couple of patients that we observed on the combination, in addition to some other case reports and case series that had started to come out in small numbers, we wanted to look back at our large cohort of patients at Memorial Sloan Kettering to see if we could really get a better sense of the numbers. How many patients at Sloan Kettering with uterine sarcomas have BRCA alterations? Are they generally somatic or germline? Are there unique features about these patients in terms of their clinical characteristics? How many of them have received PARP inhibitors, and if so, is this just luck that these three patients did so well, or is this really a good treatment option for patients with BRCA-altered uterine sarcomas? And so we did this retrospective analysis identifying the patients at Sloan Kettering who met these criteria. So in total, we found 35 patients with uterine sarcomas harboring BRCA alterations, and the majority were leiomyosarcoma, about 86% of them had leiomyosarcoma, which is interesting because there are other uterine sarcomas, but it does seem like BRCA alterations tend to be more often in the leiomyosarcomas. And 13 of these patients with uterine leiomyosarcoma were treated with PARP inhibitors in the recurrent or metastatic setting with about half of those patients having an overall response, so that's a significant tumor shrinkage that sustained, and a clinical benefit rate of 62%. And if we look at the patients that had these BRCA2 deep deletions, which was the patient I had that had this amazing response, the overall response rate jumped to 60% and the clinical benefit rate to 80%. And we defined clinical benefit rate as having maintained on the PARP inhibitor without evidence of progression at six months. So this is really impressive for patients with a difficult to treat disease. And we couldn't do a randomized controlled trial comparing it to chemotherapy, but looking retrospectively at outcomes on chemotherapy studies, this was very favorable, particularly because many of these patients were heavily pretreated. So to get a sense of, you know, how this might compare to chemotherapy, we tried to use patients as their own internal controls, and we looked at how long patients were maintained on the PARP inhibitor as compared to how long they were on the treatment just prior. And we used a ratio of 1.3 to say if they were on the PARP inhibitor for 1.3 times what their previous treatment was or longer, that is pretty clearly better, more of a benefit from that regimen. And the majority of patients did meet that bar. So 58% had a PFS ratio greater than 1.3, and the average PFS ratio was 1.9, suggesting, you know, you would expect the the later lines of therapy to actually not work as well, but this suggests that it's actually working better than the immediately prior line of therapy, to me, suggesting that this is truly a good treatment option for these patients. Dr. Rafeh Naqash: Very interesting. And you mentioned that individuals with tumors having deep deletions were probably more responsive. How did you figure out that there was biallelic loss or deep deletions? Was that part of an extended analysis that was done subsequently? Dr. Alison Schram: So the deletions reported on our report, if it's a biallelic deletion, that is the one biallelic molecular alteration that would be reported. So those are, by definition, biallelic, and I think that that may be one of the reasons that's a good biomarker. But also, what's interesting is that if you have both copies deleted of BRCA, you can't develop reversion mutations. So one of the the known mechanisms of resistance to PARP inhibitors in patients who have BRCA alterations are something called a reversion mutation where, if you have a frameshift alteration, for example, in BRCA that makes BRCA protein nonfunctional, you can develop a second mutation that actually puts the DNA back in frame, and a functional protein is now made. And so a mechanism of resistance to PARP inhibitors is actually reverting BRCA to a wild-type protein, and then BRCA's synthetic lethality no longer makes sense and is no longer effective. But if you've deleted both copies of BRCA, you don't have the ability to restore the function, and you can't develop reversion mutations. And that's perhaps why, you know, my patient and others have had these prolonged responses to PARP inhibitors because you don't have the same ability to develop that mechanism of resistance. Dr. Rafeh Naqash: I remember thinking a year and a half back, I had an individual with prostate cancer and with BRCA2, and using liquid biopsy, I had a reversion mutation that we caught. In your practice, have you seen the utility of doing the serial liquid biopsies in these individuals to catch these reversion mutations? Dr. Alison Schram: Yes, absolutely. And in patients that have the ability to develop a reversion mutation, serial cell-free DNA can catch it, but the caveat is that it doesn't always. So if you see an acquired reversion mutation in cell-free DNA, that can be helpful, particularly if you're planning on putting the patient on another line of therapy that might require a dysfunctional BRCA. So if you're putting them on a clinical trial with a PARP combination and the rationale is that they're sensitive because they don't have a functional BRCA, you would want to know if they developed a reversion mutation, and serial cell-free DNA can definitely identify these reversion mutations. Some of the major clinical trials in ovarian cancer have done serial cell-free DNA and have demonstrated the utility of that approach. The caveat is that some of these reversion mutations are not readily caught on cell-free DNA because they're more complex reversion mutations, or they're not, the part of the gene that develops the reversion mutation is not tiled on the panel. And so it doesn't always catch the reversion mutations. Also, depends on the cell-free DNA shedding, depends on the tumor volume and other factors. And we published a related paper of a patient, it was a really interesting case of a patient with prostate cancer who was on a PARP inhibitor and developed what appeared to be a single reversion mutation on one sample, had negative cell-free DNA, single reversion mutation in a tissue biopsy, and then developed disease progression. And we did an autopsy, and the patient kindly consented to an autopsy, and at the time of autopsy, there were 10 unique reversion mutations identified across 11 metastases. So almost each metastasis had a unique reversion mutation, and only one of them had been seen premortem on a tissue biopsy and not on a cell-free DNA. But that autopsy really drove home to me how much we're missing by doing clinical testing in real time and we really don't know the entire genomic complexity of our patients by doing single samples. And theoretically, cell-free DNA can catch DNA from all the metastases, so you might think that that would be a solution, and it definitely can catch reversion mutations that are not seen in a single biopsy, but you really need to do it all. I mean, you need to do the tissue biopsy sampling, you need to do cell-free DNA, and probably one cell-free DNA test is not enough. Dr. Rafeh Naqash: Thank you, again, for that very nice explanation. Now, one quick provocative question. I remember when I was training, the lab that I used to work in, they used to do a lot of phosphorylation markers for DNA damage response, like phospho NBS, RAD51. Have you seen anything of that sort on these biallelic BRCA mutations where tumors are responding, but they also have a very high signature on the phosphorylation side, and it may or may not necessarily correspond to HRD signatures, but have you noticed or done any of that analysis? Dr. Alison Schram: I think that it would be great to do that analysis. And some of the work we're doing now is actually trying to dig a little bit deeper in our cohort of patients to understand are these HRD-positive tumors? Does HRD positivity correlate with response to BRCA alterations? In terms of the functional assays, I would love to be able to do a functional assay in these samples. One of the challenges is that this was a retrospective study and many of the patients were previously treated as standard of care or off-label with these agents, and so we didn't have prospective tissue collection, and so we're really limited by the tissue that was collected as part of standard of care and the consent forms that the patient signed that allow us to do genomic and molecular testing on their samples. So, I think that is hopefully future work that we will do and others will do. Dr. Rafeh Naqash: Sure. Shifting gears to your career trajectory, I'd like to spend a couple of minutes there before we end the podcast. So Dr. Schram, you've obviously been a trailblazer in this space of drug development, early-phase trials. Can you give us a brief synopsis of your journey and how you've successfully done what you're doing and what are some of the things that drive you? Dr. Alison Schram: Well, thank you for saying that. I don't know if that's true, but I'll take the bait. I've been interested in oncology since college and was always very interested in not only the science of oncology but of course, treating patients. And in medical school, I did basic science research in a laboratory and it was very inspiring and made me want to do research in oncology in addition to clinical care. When I became an oncology fellow, I was presented with a very difficult question, which is, “Do you want to be a lab PI and be in the lab, or do you want to do clinical care and clinical research?” And I couldn't choose. I found a mentor who thankfully really had this amazing vision of combining the two and doing very early drug development, taking the data that was being generated by labs and translating it into patients at the earliest stage. So, you know, phase one drug development in molecularly targeted therapies. And so I became very interested as a fellow in early drug development and this ability to translate brand new molecular insights into novel drugs. And I joined the- at Sloan Kettering, there was the Early Drug Development, it was actually a clinic, it was called something different, and it was very fortuitous. My last year of fellowship, the clinic became its own service with the ability to hire staff at Sloan Kettering, and I was the first ever hire to our Early Drug Development Service. And that really inspired me to try and bring these drugs to patients and to really translate the amazing molecular insights that my colleagues here at Sloan Kettering are discovering, and you know, of course, at other institutions and in pharma. And you know, there 's been an amazing revolution in in drug development over the last several years, and I feel very grateful that I've been here for it. You know, I've been able to take the brilliant insights from my colleagues and put these drugs in patients, and I have the amazing privilege of watching patients in many cases that benefit from these treatments. And so I do mostly phase one drug development and molecularly targeted therapies, and truthfully, I am just very fortunate to be around such brilliant people and to have both patients and labs trust me to be able to deliver these new drugs to patients and hopefully develop better drugs that move forward through FDA approval and reach patients across the country. Dr. Rafeh Naqash: Thank you so much. That was very nicely put. And hopefully our trainees and junior faculty find that useful based on their own career trajectories. Thank you, Dr. Schram, for joining us today. Hopefully, we'll see more of your subsequent work in JCO PO. Thank you for giving us all these insights today. Dr. Alison Schram: Thank you for having me. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Alison Schram Disclosures Consulting or Advisory Role Company: Mersana, Merus NV, Relay Therapeutics, Schrodinger, PMV Pharma ,Blueprint Medicines, Flagship Pioneering, Redona Therapeutics, Repare Therapeutics, Endeavor BioMedicines Research Funding Company: Recipient: Your Institution  Merus, Kura, Surface Oncology, AstraZeneca, Lilly, Pfizer , Black Diamond Therapeutics, BeiGene, Relay Therapeutics, Revolution Medicines,  Repare Therapeutics, PMV Pharma, Elevation Oncology, Boehringer Ingelheim Travel, Accommodations, Expenses Company: PMV Pharma 

Does this sound familiar? You keep hearing that the only way to thrive as a highly sensitive or neurodivergent leader is to just “toughen up” and push through—so you try to fit into that mold, but end up feeling exhausted, misunderstood, and on the edge of burnout. It's frustrating, right? You're told your sensitivity holds you back, but all that's doing is making you question your worth and lose touch with your real strengths. What if embracing your unique wiring is actually the secret to authentic, impactful leadership (and way less burnout)? In this episode, you will be able to: Discover strategies that turn high sensitivity into a leadership superpower for more authentic and effective influence. Unlock the unique advantages neurodivergent leaders bring that boost innovation and team success in unexpected ways. Learn how to recognize early signs and create habits that prevent burnout before it takes hold in neurodivergent professionals. Embrace neurodiversity to build a workplace culture that values different minds and drives inclusive collaboration. Harness the power of empathy to transform leadership style and deepen connections that inspire lasting team loyalty. My special guest is Rachel Radway Rachel Radway is a certified leadership coach, mentor, speaker, and author with 25+ years' experience in corporate leadership roles in startups, national nonprofits, and global enterprises. Rachel helps high-achieving, highly perceptive and neurodivergent clients learn to lead with confidence, clarity and authenticity—and without burning out. Her book, Perceptive, has received endorsements and rave reviews from leaders from diverse backgrounds across industries. The key moments in this episode are:00:01:13 - Rachel Radway's Background and Purpose of Her Book "Perceptive" 00:07:33 - The Meaning Behind the Book Title "Perceptive" and Reframing Sensitivity 00:11:34 - Recognizing High Sensitivity and Neurodivergence in Yourself and Others 00:14:41 - Understanding High Sensitivity and Neurodivergence 00:17:00 - Navigating Disclosure and Accommodations in the Workplace 00:20:31 - Leveraging Neurodivergent Strengths in Leadership and Teams 00:24:00 - Creativity, Pattern Recognition, and Inclusion in the Workforce 00:27:05 - The Impact of Global Culture on Sensitivity and Inclusion 00:29:07 - Understanding Empathy and Cultural Sensitivity in Leadership 00:31:35 - The Challenges of Burnout for Highly Sensitive and Neurodivergent Leaders 00:37:26 - Strategies to Prevent Burnout in Neurodivergent and Highly Sensitive Individuals 00:40:47 - Embracing Neurodiversity and Cognitive Diversity in the Workplace 00:42:13 - Leveraging Perceptiveness as a Leadership Superpower 00:43:06 - Unlocking Blue Ocean Strategies Through Perceptive Leadership 00:44:04 - Exclusive Insights: Leaders Unlocking Perceptive Superpowers 00:44:48 - Amplifying Impact: Sharing and Supporting Leadership Growth Listen to the episode featuring Minette Norman to learn more about inclusion at work and psychological safety. Take the online high sensitivity assessment at sensitivityresearch.com to determine if you are highly sensitive. Purchase and read Rachel Radway's book, Perceptive, for insights on turning sensitivity into a leadership advantage. Access the exclusive Patreon interview for additional behind-the-scenes content with Rachel Radway.Subscribe to the podcast, leave a review, and share this episode with someone who might need to hear it. Your support helps the community grow and keeps these important conversations going. If you need professional help, such as therapy: https://www.betterhelp.com/difference If you are looking for your next opportunity, sign up for Lori's Masterclass on Master the Career Pivot: https://www.loriadamsbrown.com/careerpivot Difference Makers who are podcast listeners get 10% offf with the code: DIFFERENT Learn more about your ad choices. Visit megaphone.fm/adchoices

Discover the economic impact of hospitality and accommodations taxes in Greenville County. Learn how visitor spending funds Unity Park, The Well, the Swamp Rabbit Trail & more.Links:Learn more about Heath Dillard and his team's work at VisitGreenvilleSCListen to our previous overview of A-Tax and H-TaxListen to Heath's previous appearance on Simple Civics (Nov 2023)Follow Simple Civics: Greenville County on LinkedInFollow Greater Good Greenville on LinkedInSign up for a free book subscription for your child with Dolly Parton's Imagination Library_Produced by Podcast Studio X.Simple Civics: Greenville County is a project of Greater Good Greenville.Get in touch.Support Simple Civics with a tax-deductible contribution.Sign up for the Simple Civics newsletter.

Ready for a travel experience where the journey is just as breathtaking as the destination? Join Ken from RTE-Travel Talk as he sits down with global travel expert Andy Magistrale of Cruise and Travel Specialists to dive into the world of luxury biking adventures. In this episode, Andy shares his insight on two of the best names in active travel—Backroads and VBT (Vermont Bicycling Tours). With 85 countries visited and decades in the industry, Andy reveals how these immersive cycling tours combine fitness, culture, cuisine, and scenic exploration into one unforgettable experience. Whether you're a casual rider or a cycling enthusiast, you'll discover how Backroads and VBT make it easy to explore the world at your own pace—with support every step of the way.

Hosts Claire Deason and Nicole LeFave welcome Littler attorney Alexis Knapp for a deep dive into the world of leave and accommodations. From the surge in mental health-related requests to the role of return-to-work policies in leave requests, Alexis shares what it's like to be in the thick of it – fielding everything from open-ended FMLA certifications to AI-generated accommodation requests. The conversation explores how the post-COVID workplace has reshaped employee expectations and how employers are responding. They also dig into how employers are handling a rise in tricky or unexpected leave scenarios and options for responding. Whether it's navigating intermittent leave, decoding vague medical notes, or figuring out what to do when someone's out on leave but posting vacation selfies, this episode offers a look at the realities employers are navigating. https://www.littler.com/news-analysis/podcast/littler-lounge-pull-chair-lets-talk-leave-and-accommodations

Happy Birthday to Bryan! Fresh off his first week at the Edinburgh Fringe, Bryan tells us about the hustle it takes to perform at the world's largest performing arts festival. Erin saw the musical Some Like It Hot and has now been inspired to sign up for tap classes. Bryan explains the UK's Online Safety Act which now requires people to upload personal documents in order to view adult websites. Erin calls out Superintendent of Public Instruction Ryan Walters for watching porn during a work meeting, and celebrates Rhode Island for being the first state to provide workplace accommodations for menopause. For tickets to Bryan's show visit www.bryansafi.comSee omnystudio.com/listener for privacy information.

Dr. Sumanta (Monty) Pal and Dr. Kimmie Ng discuss the disturbing rise of early-onset gastrointestinal cancers, the unique challenges faced by younger patients, and key research that is shedding light on potential drivers of early diagnoses in colorectal cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello, everyone. I'm Dr. Monty Pal, and I'm a medical oncologist and professor and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. I'm really delighted to welcome you all to the ASCO Daily News Podcast as the show's new host. I'll be bringing you discussions with leaders in the oncology space on a variety of topics. I've been working hard with the ASCO team on picking the ideal topics to bring to you, and I'm really delighted to introduce my first guest, a dear friend, Dr. Kimmie Ng, to discuss this huge problem that we're seeing nowadays of early-onset GI cancers. Dr. Ng is the associate chief of the Division of Gastrointestinal Oncology at the Dana-Farber Cancer Institute, and she's an associate professor of medicine at Harvard Medical School in Boston. She serves as co-director of the Colon and Rectal Cancer Program. She's also the founding director of the Young-Onset Colorectal Cancer Center at Dana-Farber. I'm sure we'll talk a little bit about that today.  Just to note, our full disclosures are available in the transcript of this episode.  Dr Ng, it's so great to have you on the podcast. Thanks so much for joining us. Dr. Kimmie Ng: Thank you so much for having me. It's great to be here. Dr. Sumanta (Monty) Pal: I'm going to refer to you as Kimmie, if you don't mind, for the rest of the podcast here. Please, we'll go by first names, if you don't mind.  Your research has really done so much to help improve our understanding of early-onset GI cancers. You've done a lot of work to increase awareness in this space. I don't think there's a couple of months that passes by when I don't see you on television on Good Morning America or other shows really broadcasting this really critical message. I think there's a certain sensitivity that we all have to this issue, right? I mean, because receiving a cancer diagnosis at any age is very challenging, but I'm sure that young patients who face a colorectal cancer diagnosis have some very unique challenges. Could you give us a sense of some of those? Dr. Kimmie Ng: I think the other reason why so many people are interested in this and feel touched by this is that it's not just gastrointestinal cancers that are increasing in young people, but actually a multitude of different cancers have been rising in young individuals. And while it is difficult at any age to receive a cancer diagnosis, we do all know that young people getting a diagnosis like this do face unique challenges. Studies have shown that over 80% have children under the age of 18 when they are diagnosed with colorectal cancer, for example, under the age of 50. And many experience career and education disruptions. They are in what we call the ‘sandwich generation,' where they're not only taking care of young families or starting to think about starting a young family, but they're also taking care of elderly parents. So it's just a very busy stage of life, and to then be facing a usually terminal cancer diagnosis, it is extremely challenging. The other factors that we've seen that seem to be unique or more prevalent in young patients is that there are higher levels of psychosocial distress, depression, and anxiety, and a majority of patients do need medical attention and treatment for those things, whether it's medication treatment or whether it's counseling or support from psychosocial oncologists. And so the other big issue is fertility. We know that so many of the treatments that these young patients receive do permanently and negatively impact fertility. And for a person who is young, who may still be trying to expand their family or again start a family, it is very important that these young patients do receive counseling about fertility preservation prior to starting treatment. Dr. Sumanta (Monty) Pal: You know, it's so interesting you bring this up, and I think about a patient who's in their 40s diagnosed with this disease. They're in the same demographic as I am, as you are. You know, I'm 44 years old, and you know, I'm thinking about my 11- and 12-year-old and my aging parents, right? I mean, the dilemmas that you highlighted are precisely what I'm facing in life, and it's so true, right? If I had to take my day-to-day and superimpose on that a colorectal cancer diagnosis, it would just be problematic in so many spheres, so many spheres. Dr. Kimmie Ng: Absolutely. And because we did think going into this, starting our Young-Onset Colorectal Cancer Center, that these patients will need unique supports, we did conduct a qualitative study and held some focus groups of young-onset colorectal cancer patients as well as their caregivers. And we really identified four primary themes that I think reflect a lot of the experience of patients with cancer, no matter what type of cancer when they're diagnosed young. And the first is the need, feeling overwhelmed by the healthcare system, and the need for patient navigation. As we know, a lot of these patients are previously healthy before they're facing this very serious diagnosis. The second is the need for peer-to-peer support, where they really value connecting with other young patients going through a similar experience. The third, we talked about already, the need for kind of formal psychosocial support in the form of psychosocial oncologists or psychiatrists or social workers. And the last is an interest in research. They are really very invested in getting germline genetic testing as well as somatic genomic profiling to help guide their therapy. Dr. Sumanta (Monty) Pal: That's really encouraging to hear that they themselves are interested in participating in research. I mean, obviously, that's a great way to move the field forward. I view your area of work here as being such a vexing problem because no matter what way you slice it, young-onset colorectal cancer still remains a relatively small proportion of all diagnoses. So how do you go about studying this phenomenon? I mean, it must be challenging to really sort of investigate underlying causes when ostensibly this is still a small piece of the pie. Dr. Kimmie Ng: That is such a great question and is one of the challenges me and my research team think about every single day. As you mentioned, one of the major barriers is that although these cancers are rising in young people, the absolute number of patients being diagnosed is still relatively small, and if it's going to take large scale epidemiologic studies to really understand, for example, what the dietary and lifestyle risk factors are, you need a considerable number of patients in order to have enough power to reach definitive conclusions.  And so this is where it is so important to collaborate. Any single institution is not going to see enough young-onset patients with colorectal cancer to be able to do this work on their own. And so I have really been intent on establishing an international prospective cohort study of patients with young-onset colorectal cancer so that we can increase the numbers of patients we partner with to try to answer these questions, but also so that we can study this on a global scale, because unfortunately this is not something that's just plaguing the United States. It is actually happening in multiple countries around the world. So that is one barrier.  The second, I would say, is that we think it's early life exposures to whatever environmental factor it is that's causing the rise that is likely contributing the most. And so if you imagine how difficult it would be to start studying individuals from when they're children through adolescence, through adulthood, and then all the way until a cancer diagnosis is obtained, a study like that would take too long, would cost too much, and really wouldn't be feasible. So we need to think of alternative ways to really try and answer this question of what is driving this rise in young-onset colorectal cancer. Dr. Sumanta (Monty) Pal: Honestly, Kimmie, this seems like almost an unfair question in the context of what you just mentioned, the challenges in terms of ascertaining causality, right? I'll tell you, I cheated a little bit ahead of this podcast. Kimmie and I had dinner together in Los Angeles a couple months ago. She came out to deliver a Presidential Lectureship at City of Hope. We were delighted to have her. And we did have a couple of thoughts exchanged over potential drivers of these early diagnoses, leaning on perhaps one of the things that you and I are both interested in, the microbiome. But amongst all these things, vitamin D, microbiome, etc., and I won't hold you to this, do you have at least a general sense of what might be contributing to this early-onset phenomenon? Dr. Kimmie Ng: Yeah, as we talked about during my visit there to City of Hope, we do hypothesize that it is a complex interaction between our exposome, which is everything we are exposed to in our environment, which does include diet and lifestyle factors, interacting with host immunity and antitumor immunity, and as well as the microbiome and shaping the composition and diversity of the gut microbiome that are likely interacting to increase susceptibility to colorectal cancer at a younger age. And I will say one of the biggest discoveries, if you will, about what might be driving young-onset colorectal cancer was published a few months ago in Nature. And that paper identified a specific mutational signature caused by the genotoxin colibactin, which is often produced by an organism called pks+ E. coli, as being much more prevalent in younger patients with colorectal cancer than older patients. And so while it doesn't explain necessarily all of young-onset colorectal cancer and why it's rising, it does give us a clue that the microbiome is likely very important in perhaps why this is rising in young people. Dr. Sumanta (Monty) Pal: After you mentioned it, I went back and dove deep into that paper. I was fascinated, fascinated by the content there. And this is just a massive exploration across thousands of patients worldwide. So, I mean, if there is a way to get at least some hint of what's driving this phenomenon, I suppose that's it. So thank you for pointing me in the direction of that manuscript. Now that we've addressed the issue of diagnosis, if we could just, you know, verge on the topic of treatment, right? And this is something that I struggle with. When I have my young patients with kidney cancer, I don't know necessarily that my treatment paradigm changes a whole heck of a lot. I guess what I will say is I might be a little bit more aggressive about concepts like definitive management with surgery. I suppose perhaps their treatment tolerance is a little bit higher. But tell us about the setting of young-onset colorectal cancer. Is the philosophy any different in terms of the actual sort of management of these patients? Dr. Kimmie Ng: That's a great question, and actually I was honored to participate in the first international consensus guidelines group to try to come up with uniform recommendations for how to treat young patients with colorectal cancer. And you know, the overall consensus is just as you said, the medical care of these young patients right now is really not that much different than that of an older patient with colorectal cancer. There are a couple of distinctions. One is that all young patients should get germline genetic testing, given that there is a higher prevalence of pathogenic germline variants when you are diagnosed at a young age. And the second is what we've already talked about, which is that all young patients should be referred for counseling about fertility preservation prior to starting treatment. But otherwise, the chemotherapy regimens recommended, you know, surgery, radiation, all of that seems very similar to older patients. I will say that because most of our young patients with colorectal cancer are diagnosed with left-sided cancers, including rectal cancers, where some of the treatment may be morbid and result in lifelong complications, we do consider de-escalation of therapy and try to consider the long-term implications when it's safe to do so and won't compromise outcomes. The other concerning thing is that younger patients don't necessarily have a better prognosis than older patients. And multiple studies have shown this, that even though we both often treat younger patients more aggressively – they more often receive multi-agent chemotherapy, and more often undergo surgery and radiation – their survival is not necessarily correspondingly better than an older patient with colorectal cancer. So that suggests to us that maybe these cancers are indeed biologically different and perhaps more aggressive or perhaps less responsive to treatment. And so that is some of the focus of our research too, to understand what is actually different about these cancers and how they respond to treatment. Dr. Sumanta (Monty) Pal: It's such a paradox, isn't it, right? Because you just brought this to my mind. I guess on the one hand, our younger patients may be able to tolerate perhaps a greater amount of chemotherapy, targeted therapy, etc. But you're absolutely right. I mean, they do sort of have these lingering issues with side effects that may persist for much longer than the 80- or 90-year-old that we're treating in the clinic. I mean, these tend to be sort of lifelong consequences and sequelae that they're dealing with. So that really does evolve to be a challenge. You've kind of changed my mindset there a little bit. Dr. Kimmie Ng: Yeah, I do think survivorship issues and long-term complications of therapy do need to be considered, especially for a young person who we hope will live a very, very long time. And so part of the work that our Young-Onset Colorectal Cancer Center is doing, we are participating in a pilot navigation study where we navigate patients to survivorship earlier than we typically would, perhaps, for an older patient. And that's so we can get a head start on addressing some of those potential complications of therapy and hopefully mitigate them so that they don't become an issue long term. Dr. Sumanta (Monty) Pal: Do you think there's a role for de-escalation studies formally in these young populations of patients? Dr. Kimmie Ng: I think de-escalation studies are important overall, and specifically for locally advanced rectal cancer, which again is one of the most common types of colorectal cancer diagnosed in our young patients, there are certain populations that may be able to forgo the radiation treatment to the pelvis, for example, and there's more and more patients who now may become candidates for non-operative management where they may not necessarily need to have their rectal cancer surgically removed. And elimination potentially of both of those modalities of treatment can really avoid some of the most serious and morbid complications that often occur with these treatments. Dr. Sumanta (Monty) Pal: Really interesting. Now, this is not and will never be a political podcast, but you know, obviously we're dealing with the consequences of changes on funding and so forth that have evolved over time. And I think it's worth sort of speculating how the landscape of research may change on account of that. Could you comment perhaps a little bit on how some of the funding cuts that we've seen recently at the NIH might affect the body of work that you're so integrally involved in? Dr. Kimmie Ng: I am honestly very worried about the current funding environment. Colorectal cancer is the third most commonly diagnosed cancer among men and women in the United States and globally, and when you combine men and women together, the second leading cause of cancer death. But proportionally, we receive much less funding for colorectal cancer compared to other cancer types. And my thoughts have always been that perhaps this is because there is this stigma around colorectal cancer and maybe some of the symptoms associated with colorectal cancer. And so on top of that, to have additional challenges in obtaining funding, I worry what it will do to the pace of progress for especially young patients with this disease. Also, because of some new stipulations that perhaps international collaborations are being discouraged, I also worry about that aspect of it because young-onset colorectal cancer and gastrointestinal cancers in general is a global phenomenon happening in multiple countries around the world. And if we are to understand what the environmental factors are affecting the different rates of rise in these different countries, we do so much need that international collaboration. So yes, I am worried, and I do hope that conversations like this will spark an awareness of the need for more funding and continued funding into this disease. Dr. Sumanta (Monty) Pal: I will say that, and the audience can't see this because this is an audio program, but I'm wearing my Southwest Oncology shirt here, a SWOG, and it's one of the National Cancer Institute-funded cooperative groups. And you know, I was recently dismayed to find that, you know, funding got cut for international collaborations and enrollment in South America and Latin America. And this was traditionally actually a mainstay of our enrollment for many trials, including trials in rare cancers that present themselves in younger patients in the GU space. So, I completely agree with you. We've got to do something to address this funding issue to make sure that this body of work, both yours and mine, continues, without a doubt. Kimmie, this has been a delightful conversation. I really want to thank you for, you know, leading the charge in the young-onset colorectal cancer space, and you've done so much tremendous work here. Dr. Kimmie Ng: Thank you for having me. Dr. Sumanta (Monty) Pal: If you value the insights that you hear on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. And again, thank you for joining us today. 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. Find out more about today's speakers:   Dr. Sumanta (Monty) Pal @montypal Dr. Kimmie Ng @KimmieNgMD Follow ASCO on social media:    @ASCO on Twitter   ASCO on Bluesky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Sumanta (Monty) Pal: Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis Dr. Kimmie Ng: Honoraria: Seagen, GlaxoSmithKline Consulting or Advisory Role: CytomX Therapeutics, Jazz Pharmaceuticals, Revolution Medicines, Abbvie, Bayer, Pfizer, Agenus, Johnson & Johnson/Janssen, Etiome, AstraZeneca Research Funding (Inst.): Pharmavite, Janssen Other Relationship: JAMA

Breaking Down Internalized Ableism  Summary In this conversation, Patricia explores the concept of internalized ableism, particularly among neurodivergent individuals. She discusses how societal stigma and expectations can lead to negative self-perceptions and feelings of inadequacy. Patricia shares personal experiences and insights on how internalized ableism manifests in various aspects of life, including relationships, self-acceptance, and the pressure to conform to neurotypical standards. She emphasizes the importance of unlearning these hurtful beliefs and embracing one's neurodivergent identity with compassion and understanding.   HIGHLIGHTS   ·       Internalized ableism is the unconscious adoption of negative beliefs about oneself due to societal stigma. ·       Neurodivergent individuals often feel pressure to conform to neurotypical standards, which can lead to trauma. ·       Resting is a valid need and should not be seen as a failure. ·       Asking for accommodations is essential for well-being and should not induce guilt. ·       The concept of 'high functioning' can be harmful and does not reflect true capabilities. ·       Time agnosia is a common experience for neurodivergent individuals. ·       Self-compassion is crucial in overcoming internalized ableism. ·       Relationships can be affected by the fear of being a burden. ·       Unlearning internalized ableism involves recognizing and challenging societal expectations. ·       Embracing neurodivergence includes acknowledging strengths and practicing self-acceptance. 115 SPECIFIC POINTS DISCUSSED 1.     How internalized ableism shows up in everyday life o   Masking, pushing through burnout, or feeling "lazy" when you're resting. 2.     Messages we absorbed growing up o   From school, parents, peers, or media about being "too much," "distracted," "weird," or "wrong." 3.     Perfectionism and people-pleasing as survival o   How needing to be “better” or “easy to manage” is often rooted in internalized shame. 4.     The trap of “not disabled enough” or “faking it” o   How we invalidate our own struggles because we don't “look” stereotypically disabled. 5.     ADHD, autism, OCD & “high-functioning” narratives o   The myth of being “high functioning” and how it reinforces ableist expectations. 6.     Feeling guilt for needing accommodations or rest o   That voice that says “you're being difficult” when you ask for what you actually need. 7.     Shame around executive dysfunction o   Struggling to start tasks, follow through, or manage time — and blaming yourself. 8.     Rejecting your own needs to fit in o   Forcing eye contact, avoiding stimming, hiding rituals, not using noise-canceling headphones in public, etc. 9.     The pressure to be “independent” all the time o   How internalized capitalism + ableism equates needing support with being a failure. 10.  Comparing yourself to neurotypical peers ·       Especially in productivity, relationships, or emotional regulation. 11.  “If I can do it sometimes, I should always be able to” myth ·       Inconsistent ability = inconsistent worth? Nope. Talk about spoon theory and fluctuating capacity. 12.  How OCD-specific traits are misunderstood or mocked ·       And how that seeps into how you see yourself (e.g., feeling “crazy,” “irrational,” or “a burden”). 13.  Internalized ableism in dating & relationships ·       Fear of being too much, too emotional, or too rigid — and minimizing yourself as a result. 14.  How healing looks like reclaiming your needs unapologetically ·       Self-accommodation, boundaries, rest, and neurodivergent joy as rebellion. 15.  Relearning self-compassion and identity pride ·       Ending with hope: unmasking, connecting with community, and defining success on your own terms.    SOUND BITES ·       "Rest is resistance." ·       "You are not broken." ·       "You deserve rest, joy, and support."    SENSITIVITY IS NOTHING TO APOLOGIZE FOR; IT'S HOW YOUR BRAIN IS WIRED You are not broken. You were shaped by systems that weren't built for you. You deserve rest, joy, and support exactly as you are.    CHAPTERS (please add time for addition of introduction) 00:00 Understanding Internalized Ableism 02:40 The Impact of Societal Expectations 05:31 Navigating Personal Experiences with Internalized Ableism 08:18 The Struggle for Accommodations 10:55 Executive Dysfunction and Inconsistent Abilities 14:01 The Pressure of Productivity 16:53 Feeling 'Not Enough' in Neurodivergence 19:43 Unlearning Internalized Ableism 22:27 Building Self-Compassion and Acceptance  PODCAST HOST Patricia was a Licensed Clinical Social Worker for over 17 years, but she is now exclusively providing coaching. She knows what it's like to feel like an outcast, misfit, and truthteller.  Learning about the trait of being a Highly Sensitive Person (HSP), then learning she is AuDHD with a PDA profile, OCD and RSD, helped Patricia rewrite her history with a deeper understanding, appreciation, and a sense of self-compassion.  She created the podcast Unapologetically Sensitive to help other neurodivergent folks know that they aren't alone, and that having a brain that is wired differently comes with amazing gifts, and some challenges.  Patricia works online globally working individually with people, and she teaches Online Courses for neurodivergent folks that focus on understanding what it means to be a sensitive neurodivergent. Topics covered include: self-care, self-compassion, boundaries, perfectionism, mindfulness, communication, and creating a lifestyle that honors you LINKS Rest Is Resistance: Free yourself from grind culture and reclaim your life by Tricia Hersey. Neurodivergent Online Course-- https://unapologeticallysensitive.com/neurodivergent-online-courses/ Receive the top 10 most downloaded episodes of the podcast-- https://www.subscribepage.com/e6z6e6  To write a review in itunes: click on this link https://itunes.apple.com/us/podcast/unapologetically-sensitive/id1440433481?mt=2 select “listen on Apple Podcasts” chose “open in itunes” choose “ratings and reviews” click to rate the number of starts click “write a review”   Website--www.unapologeticallysensitive.com Facebook-- https://www.facebook.com/Unapologetically-Sensitive-2296688923985657/ Closed/Private Facebook group Unapologetically Sensitive-- https://www.facebook.com/groups/2099705880047619/ Instagram-- https://www.instagram.com/unapologeticallysensitive/ Youtube-- https://www.youtube.com/channel/UCOE6fodj7RBdO3Iw0NrAllg/videos?view_as=subscriber Tik Tok--https://www.tiktok.com/@unapologeticallysensitiv e-mail-- unapologeticallysensitive@gmail.com Show hashtag--#unapologeticallysensitive Music-- Gravel Dance by Andy Robinson www.andyrobinson.com  

✅ Learn more about the course here: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.agentsofchangeprep.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Meagan Mitchell, the founder of Agents of Change, is a Licensed Clinical Social Worker who has been providing individualized and group test prep for the ASWB for over 8 years. From all of this experience helping others pass their exams, she created a course to help you prepare for and pass the ASWB exam! Find more from Agents of Change here: ► Agents of Change Website: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://agentsofchangeprep.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ► Facebook Group: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.facebook.com/groups/aswbtestprep⁠⁠⁠⁠⁠⁠⁠⁠ ► Instagram: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.instagram.com/agentsofchangeprep/

What are A-tax & H-tax? Learn how hospitality and accommodations taxes in Greenville County fund things you love, from the Swamp Rabbit Trail to local festivals._Produced by Podcast Studio X.Simple Civics: Greenville County is a project of Greater Good Greenville.Get in touch.Support Simple Civics with a tax-deductible contribution.Sign up for the Simple Civics newsletter.

This week, I sat down with Marc Fishman, and let me tell you this one's heavy. Marc's a disabled dad who's been fighting a brutal uphill battle in family court. Not because he's a bad parent. Not because he did something wrong. But because the system doesn't know what to do with someone who looks different, moves different, or needs accommodations to be a great parent. He talks about: Getting stonewalled when asking for basic disability accommodations How his rights as a dad were slowly stripped away not by evidence, but by bias And the emotional toll of being told you're “not capable” when you know damn well you are Marc isn't sitting still though. He's fighting back filing appeals, speaking out, and refusing to let the system define his relationship with his kid. This episode is about resilience, discrimination, and the raw reality of being a disabled parent in a court system that's still stuck in the past. If you've ever felt powerless, this one's for you.   Links https://newrochellepoliceabuse.com/    

Is it too early to start planning for school when summer has just begun? Not if your child has food allergies. Dr. Nikki Chase, a board-certified allergist-immunologist, joins us to share what families need to know to prepare for a safe and successful school year. From school forms and emergency plans to when to self-carry epinephrine and how to teach self-advocacy, this episode is filled with practical, real-life guidance. We discuss how to make the most of your summer doctor visits, why early planning matters, and how newer epinephrine options, like the nasal spray, may help reduce fear and delay in use. You'll also hear Dr. Chase's advice on helping kids build confidence and take ownership of their allergy care. What we cover in our episode about preparing for school with food allergies:  504 plans explained: What they are, how to request one, and why they matter for legal protection and clear school accommodations. Anaphylaxis Action Plans: What's included, how they differ from 504 plans, and why they take the guesswork out of emergencies. Epinephrine device options: From auto-injectors to nasal spray, what's available and how to choose the best fit for your child. What to work on this summer to build allergy confidence: The rules, responsibilities, and privileges kids should practice to stay safe and feel more in control. Self-advocacy & communication tips: How to help your child speak up, navigate cafeteria dynamics, and respond to food allergy bullying. More resources about back-to-school with food allergies Planning for School with Food Allergies School Plans for Students with Food Allergies Managing Allergies in Schools: A Guide for Staff Epinephrine for Anaphylaxis: What Treatments are Available? Food Allergy Treatment & Management   Produced in partnership with The Allergy & Asthma Network. Thanks to ARS Pharma for sponsoring this episode. This podcast is for informational purposes only and does not substitute professional medical advice. Always consult with your healthcare provider for any medical concerns.

In today's episode, Kristi checks into a hotel, so we discuss a range of Italian accommodations, from farm stays to hotels and monasteries. We also learn vocabulary to ask about amenities and to resolve any issues that might come up during a stay, such as asking for more towels or fixing a broken faucet.But to get the most out of Italian for Travelers, head to our website and subscribe to our premium online course. You'll get:A phone-friendly & clickable PDF of all our mini-glossaries ← the perfect travel buddy for Italian learners!Full episodes (we only stream a portion of our conversations!)Dialogue transcriptsListen-and-repeat audio glossaries (no banter, just vocabulary to practice your pronunciation)Practice lessons … and so much more!  www.PostcardsFromItalyPodcast.com Live La Dolce Vita glamor... without all the grammar :-)

If you're planning a summer trip to Ireland, you might be surprised to discover that air conditioning is not common in most accommodations. Whether you're booking a hotel, a B&B, or a self-catering cottage, it's likely the rooms won't have A/C – and that's not a mistake. It's simply because Ireland hasn't really needed it.... The post Why Don't Irish Accommodations Have Air Conditioning? appeared first on Ireland Family Vacations.

Interviewer: Dr. Lisa Meeks Interviewees:  ·       Abbey MacLellan ·       Zachary Ford ·       Marihan Farid ·       RJ Roggeveen ·       Michael Quon ·       Lynn Ashdown Description: Episode 108: ICAM Panel – Facing Ableism: What's Our Role in Building Inclusion

Join Mike and Scott as we answer your Listener Questions on today's show!  We discuss the idea of taking the Skyliner to Bar Riva for a mid-day break on the way back to Pop Century from Hollywood Studios for a family with teen boys, booking Port Adventures with Disney Cruise Line for an Eastern Caribbean Cruise, "splurging" a bit for an adults-trip for Princess Half-Marathon 2026, parade/fireworks viewing at the Magic Kingdom, and much more! Come join the BOGP Clubhouse on our Discord channel at www.beourguestpodcast.com/clubhouse!  Thank you so much for your support of our podcast! Become a Patron of the show at www.Patreon.com/BeOurGuestPodcast.  Also, please follow the show on Twitter @BeOurGuestMike and on Facebook at www.facebook.com/beourguestpodcast.   Thanks to our friends at The Magic For Less Travel for sponsoring today's podcast!

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And 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. 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. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

ReferencesBiophys J. 2013 Mar5;104(5):1049–1055Chem Phys Lipids. 2021 Aug: 238:105091PNAS 2013. November5, vol. 110 no. 45Biomolecules.2024 Feb3;14(2):184Furay, R. 1968. "Kind Woman" Buffalo Springfield/Pocohttps://music.youtube.com/watch?v=9Yl8SW5s11s&si=KYQQ0CtDyu67imSA Clarke, Nash, Hicks. 1967. "On a Carousel" Hollieshttps://music.youtube.com/watch?v=tK4_7I1YIOc&si=jwcDBSdO9KwZS8bUSchubert, F. 1815-1821. "Der Lieder"https://music.youtube.com/watch?v=tyBp3lpdi-k&si=uyqtU25uDdjRdQPA

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Bonnaroo 2025: The Festival That Ended Too Soon

Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe, wherever you get your podcasts. 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. More on today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

ReferencesJ Neuroinflammation. 2016; 13: 264.Curr Res Struct Biol. 2025 Feb 18;9:100165.Lennon/McCartney; Harrison. 1965. "Help" lp.https://music.youtube.com/watch?v=MKUex3fci5c&si=dvulEXvI8fVdDvsJRocky Marciano 1950'shttps://music.youtube.com/watch?v=NyWROU7_Vlo&si=F75EJ7sVSee3jq_2

Following our recent episode, Accuracy in Accommodations, we wanted to revisit an episode that plays a crucial role in creating accurate accommodation. Enjoy this revisit to our previous Practice in Action episode: Problem? SolvedProblem solving is an integral part of our everyday lives and a critical skill that every mental health professional must be aware of. But what is good problem solving, and how do we use it in the therapy setting. This is exactly what Ray and Paul seek to answer in their conversation today. They break down the process of problem solving, and develop guiding principles that allow us to help our clients with this crucial skill. We hope you enjoy this Practice in Action episode: Problem?… SolvedTo hear more and stay up to date with Paul Wagner, MS, LPC and Ray Christner, Psy.D., NCSP, ABPP visit our website at: http://www.psychedtopractice.com Please follow the link below to access all of our hosting sites. https://www.buzzsprout.com/2007098/share “Be well, and stay psyched” #mentalhealth #podcast #psychology #psychedtopractice #counseling #socialwork #MentalHealthAwareness #ClinicalPractice #mentalhealth #podcast

ReferencesBiochemistry. 2002 Jan 29;41(4):1398-408.ACS Omega 2021, 6, 17, 11122–11130Current Opinion in Colloid & Interface Science. 2016. Volume 22, April :99-107Langmuir 2019 35.30 9944-Guerra, DJ 2025. Unpublished Lectures.Plato 4th Century BC . Lesser Hippias dialogue.Winwood, Wood, and Capaldi. 1967. "Dear Mr. Fantasy" Live at the Canteen. lp.https://music.youtube.com/watch?v=_AUSfxQEcdw&si=XYeTQO_Ey-pESAxxHunter/ Garcia 1970. "Ripple" American Beauty lp.https://music.youtube.com/watch?v=sFBQSx_xc2o&si=86YVzrn23PbkOngZTaylor, J. 1971. "Highway Song" Mudslide Slim lp.https://music.youtube.com/watch?v=Mv4pYbRK9tg&si=1JAusoY4LMmJnDHESchmelzer, J . 1680. "Victori der Christian" from Romanesque lp.https://music.youtube.com/watch?v=n3x1dIz0LFo&si=PsflEAE18eGlJJ9y

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ReferencesMinireviews 2003. Volume 278, 47p46195-46198Biochemistry. 2002 Jan29;41(4):1398-408.Biochimica et Biophysica Acta (BBA) - Biomembranes 2011. 1808, 1, January Pages 127-139Annual Review of Biophysics2010. 39(1):207-26Langmuir 2019 35.30 9944-53.Guerra, DJ. 2025. Membrane lectures: unpublished.Fagen &Becker. 1973. Steely Dan "Reelin in the Years"https://music.youtube.com/watch?v=91XTZ92zs2w&si=wOhRhM6DcdmxQb4GPage, J.1972. "Rock n Roll" from LZIVhttps://music.youtube.com/watch?v=SRQ7-eSGBWc&si=2GWqbbGlSCj7u3hNMemphis Slim . 1959. "Steppin Out" Cream 1972 Live Cream Vol II lp.https://music.youtube.com/watch?v=OWTJVNPu_r4&si=9L2OwzXOk5N57b3Y

ReferencesBiochemistry. 2002 Jan29;41(4):1398-408.Biochem Soc Trans . 2020 Jun 30;48(3):1129-1138. Front Cell Dev Biol. 2016 Sep 12:4:97Schubert, F. 1827. Impromptus D899, No3 Op.90 in G Flat major. Khatia Buniatishvili at the piano.https://music.youtube.com/watch?v=ppc_X8qvhUI&si=K8SEAQAl3At4oZz6

What are commonly requested accommodations in the workplace? How can employers successfully hire and train neurodiverse staff? Maxwell Huffman and Jen Goubeaud of Aspiritech, Aspiritech, a quality-assurance company with over 90% of autistic employees, share their insights on these topics. Maxwell is Autistic himself and oversees operations across Aspiritech's program lines, including software quality assurance, accessibility, and data services. And Jen, who has ADHD, is the program manager for the company's accessibility program line. Welcome to Autism Tips & Tools, where we highlight the best practical guidance from previous episodes of Autism Knows No Borders. Whether you're a self-advocate, a family member, or a service provider, there's something here for you! The following clip is from our conversation with Maxwell Huffman and Jen Goubeaud, originally released on February 15, 2024.  Would you like to hear Jen and Maxwell talk about accessibility in digital spaces and how to create opportunities for neurodivergent employees to thrive? Click the link below for the full conversation and be sure to subscribe to hear more from people connected to autism inspiring change and building community.  How to Increase Neurodiversity in the Workplace | Part 1 with Maxwell Huffman and Jen Goubeaud Let's work together to transform how the world relates to autism. ----more---- We appreciate your time. If you enjoy this podcast and you'd like to support our mission, please take just a few seconds to share it with one person who you think will find value in it too. Follow us on Instagram: @autismpodcast Join our community on Mighty Networks: Global Autism Community Subscribe to our YouTube channel: Global Autism Project We would love to hear your feedback about the show. Please fill out this short survey to let us know your thoughts: Listener Survey

What's it really like to walk a long-distance trail in rural France? In this episode of Join Us in France, titled Hiking Chemin du Puy and Célé Valley, host Annie Sargent talks with Rowena Sjovall, a solo traveler from the U.S. walking the GR65 and the scenic Célé Valley route. Get the podcast ad-free Rowena shares her detailed experience hiking the Chemin du Puy, one of France's most popular pilgrimage trails. She talks about trail conditions, signage, and the variety of landscapes—rolling hills, deep river valleys, and charming medieval towns. If you've wondered about hiking from Le Puy-en-Velay toward Cahors or incorporating the lesser-known Célé Valley variant, Rowena offers honest insights. The conversation covers practical tips too. What kind of gear should you bring? How easy is it to find food and lodging? What's the vibe among other hikers? Annie asks all the right questions to help listeners decide if this kind of trip is for them. Whether you're planning a Camino in France or just curious about rural walking holidays, this episode delivers both inspiration and real-world advice. Don't forget to subscribe to Join Us in France for more episodes like this, where travel dreams and logistics meet. Perfect for slow travel lovers, Francophiles, and adventure-seekers! Table of Contents for this Episode [00:00:15] Introduction and Greetings [00:00:31] Today on the podcast [00:00:59] Podcast supporters [00:01:32] The Magazine segment [00:02:25] Annie and Rowena [00:03:11] The Crazy Adventure Begins [00:06:27] Planning the Journey [00:08:41] Navigating the Trail [00:12:45] Challenges and Perseverance [00:18:48] Starting point [00:27:14] Navigating Through Cornfields [00:27:51] Rainy Day Lunch and Milka Chocolate [00:28:44] Challenges of Finding Food and Shelter [00:29:43] Reaching the Hilltop and Meeting Fellow Travelers [00:32:48] Exploring Troglodyte Houses [00:34:07] Communal Dinners and Accommodations [00:34:51] Comfort Level at the Accommodations in the Célé Valley [00:41:14] Advice for Future Travelers [00:44:15] Planning the Next Journey [00:47:41] The hardest day [00:48:17] Concluding Thoughts and Farewell [00:48:45] Thank you Patrons [00:49:40] Tour Reviews [00:50:40] Discount for Podcast Listeners [00:51:54] Swimming in the Seine [00:56:21] Next week on the podcast [00:56:58] Copyright   More episodes about active vacations in France

In this episode of Psyched to Practice, Paul and Ray take on a conversation that hits home for educators, therapists, and parents alike—how do we know when an accommodation is actually helping? And when is it holding someone back? With clinical insight, personal stories, and a bit of humor, they break down how to tell the difference between under-accommodating, over-accommodating, and finding that “just right” fit. From executive functioning to anxiety support to college roommates, they explore how to scaffold success without doing the work for someone. Whether you're helping a student, a client, or your own child, this episode offers the clarity and strategies to make accommodations meaningful—not just habitual.To hear more and stay up to date with Paul Wagner, MS, LPC and Ray Christner, Psy.D., NCSP, ABPP visit our website at: http://www.psychedtopractice.com Please follow the link below to access all of our hosting sites. https://www.buzzsprout.com/2007098/share “Be well, and stay psyched” #mentalhealth #podcast #psychology #psychedtopractice #counseling #socialwork #MentalHealthAwareness #ClinicalPractice #mentalhealth #podcast

Joining us this week is returning guest Eric Endlich, Ph.D. Dr. Endlich is a clinical psychologist and founder of Top College Consultants®, which specializes in guiding neurodivergent students through the college application process. An advocate and expert in the field and a neurodivergent adult himself, he co-teaches a UC Irvine course for educational consultants, manages a large Facebook group for parents of neurodivergent students, and serves on advisory boards related to autism and neurodiversity. Dr. Endlich joins us this week to discuss the far too often overlooked challenges that neurodivergent students face when transitioning from high school to college. While gaining admission is one big challenge, the real challenge is succeeding once on campus, and Dr. Endlich sheds some light on some of the key differences between being college-capable and college-ready, highlighting the fact that students with learning and thinking differences are typically at much higher risk of not completing their degrees. We also explore some practical strategies to help students prepare for the increased independence and self-advocacy required in college life, with topics including building executive functioning skills in high school, the value of gap years, and how parents can gradually transition from being advocates to coaches.  Dr. Endlich even talks about how to find the right college fit and make the most of on-campus resources, especially for students needing accommodations and support programs. Whether your teen is just starting high school or gearing up for college in the upcoming fall season, this episode of the podcast truly provides some practical insights into how to foster independence! Show Notes: [2:39] - Dr. Endlich asserts that too many students focus too much on getting into college rather than graduating from it. [4:43] - Success in college requires more than just academic capability; independence and self-management skills are also important. [6:36] - College demands greater self-organization and disability accommodation compared to high school. [8:57] - Dr. Endlich argues that parents should shift from advocating for their child to empowering their independence. [10:26] - Gradually transferring daily responsibilities helps students build independence before college. [13:02] - Taking a gap year can improve college preparedness and help prevent academic burnout. [15:10] - Dr. Endlich adds that gap years can strengthen a student's portfolio and develop valuable life skills. [18:02] - Consider the long-term value of a degree and explore financial aid options. [19:51] - Dr. Endlich points out how skill development can happen during high school, gap years, or throughout college. [22:44] - Even if colleges lack support, external programs can provide assistance and guidance. [25:26] - Visiting various colleges helps students identify their preferences and find the right fit. [28:09] - It's also important to make visits to dining halls and have meetings with support staff, helping to reveal the college's suitability. [31:02] - Even without campus visits, virtual tours and accepted-student events can also offer some valuable insights. [34:58] - Bridge programs help students acclimate to college life before the official start. [36:28] - Dr. Endlich states that carefully managing the application process and having backup plans can help reduce anxiety.   Links and Related Resources: Episode 83: What Students with Disabilities Should Do When Starting College with Eric Endlich, Ph.D Episode 126: Why Self-Awareness and Self-Determination are Important for College Success with Elizabeth Hamblet Episode 156: To Test or Not to Test (ACT/SAT) in the Test-Optional Era with Annika Guy Episode 190: Should Your Teen Take a Gap Year? with Julia Rogers Top College Consultants® - Getting Into College Is the Easy Part Top College Consultants® - 6 Reasons to Consider a Gap Year   Connect with Us: Get on our Email List Book a Consultation Get Support and Connect with a ChildNEXUS Provider Register for Our Self-Paced Mini Courses: Support for Parents Who Have Children with ADHD, Anxiety, or Dyslexia    Connect with Eric Endlich, Ph.D: Eric Endlich, Ph.D's LinkedIn Page Top College Consultants® Email: eric@topcollegeconsultants.com  Phone: (833) WE-APPLY (toll free)  

Should you make special accommodations for someone with a special diet? Isha Sesay Talks Motherhood, Rebranding AreyaSee omnystudio.com/listener for privacy information.

Mary J. Goodwin-Oquendo, Esq., discusses how the dismantling of the U.S. Department of Education (DoE) may impact students with ADHD and learning disabilities who receive special education services and accommodations through IEPs and 504 Plans. ADHD Accommodations and Educational Rights: Additional Resources Free Download: Your Child's Legal Rights at School Read: “Is My Child's IEP in Danger?” Read: When Schools Resist Evaluating & Addressing Learning Disabilities eBook: The Complete IEP/504 Guide Access the video and slides for podcast episode #554 here: https://www.additudemag.com/webinar/adhd-accommodations-department-of-education-iep-504/ Thank you for listening to ADDitude's ADHD Experts podcast. Please consider subscribing to the magazine (additu.de/subscribe) to support our mission of providing ADHD education and support.