Podcasts about accommodations

The Push-Pull of ADHD and Autism: Stretching Without Breaking In this candid conversation, Patricia Young (she/her) and B Lourenco (she/her) dive deep into the realities of living with ADHD, autism, and other forms of neurodivergence. They explore the push-pull between self-accommodation and stretching ourselves, how shame and internalized ableism impact daily life, and what it means to create realistic support systems at home, in relationships, and in the workplace. Expect raw honesty, relatable stories, and practical insights for navigating neurodivergent life. WHAT YOU'LL HEAR IN THIS EPISODE · The ongoing "driver's seat battle" between ADHD and autism. · The push-pull between making accommodations and stretching ourselves beyond comfort. · Parenting a neurodivergent young adult while balancing when to push and when to allow rest. · Task initiation struggles — from making banana bread to cooking meals. · Body doubling as a powerful tool to reduce shame and spark motivation. · The "crisper/rotter" effect — guilt over wasted food and executive dysfunction. · Financial and practical impacts of task initiation challenges. · How privilege plays into having options like prepared or frozen meals when cooking feels impossible. · The cost of pushing through fatigue and flares with conditions like POTS and MCAS. · "Future me" thinking — and the difficulties neurodivergent folks have with impermanence. · Shame as the "ice cream scoop" on top of disability struggles. · Why diagnosis matters: language helps reduce shame and prevent repeating harmful patterns. · How powerlessness, and an attempt to gain autonomy can show up in small, reactive choices (like leaving a Facebook group). · Sensory sensitivities in family systems — how lack of accommodations can lead to dysfunction. · Practical accommodations for noise-sensitive parents and their kids. · Workplace challenges: 40-hour weeks, return-to-office pressures, and capitalism's rigidity. · Creative problem-solving in disabled and neurodivergent communities. · The deep fear of being uncared for and alone if we can't keep up. · Hyper-independence and isolation in the ADHD/autistic community. · Internalized ableism and the "shoulds" that drive shame and burnout. · Neurodivergence as a dynamic disability — what's possible one day isn't always possible the next. · Radical acceptance as a path toward reducing judgment and finding relief. SOUND BITES · "It begs the question of, okay, is that okay? Can we just say that's how it is?" – B Lourenco · "Instead of putting our energy into addressing the gap, folks will take the great divide and then put a scoop of shame on top of it." – B Lourenco · "All the terrible things that we tell ourselves… if I didn't have that awareness, I'd just keep repeating these patterns." – Patricia Young · "In order to truly accommodate ourselves, we have to acknowledge that it's as hard as it is and that we're as disabled as we are." – B Lourenco · "Sometimes I have to ask myself, what if what you're going through is exactly where you need to be?" – Patricia Young 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. TOPICS COVERED (please adjust for addition of introduction) 00:00 Navigating Neurodivergence: A Personal Journey 02:59 Understanding Accommodations: Balancing Needs and Expectations 05:48 The Push-Pull of Task Initiation and Self-Care 08:33 Shame and Support: The Role of Community 11:35 The Impact of Environment on Neurodivergent Individuals 14:26 Workplace Challenges: The Struggle for Accommodations 17:16 Building Bridges: Community and Creative Solutions 20:00 Radical Acceptance: Embracing Our Reality 22:48 The Journey of Self-Discovery and Identity 25:42 The Dynamic Nature of Neurodivergence 29:02 Finding Joy in the Present Moment 31:47 The Bigger Picture: Building a Better Future 34:47 Conclusion: Resources and Future Endeavors PODCAST HOST Patricia Young (she/her) 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 podcasts Unapologetically Sensitive and Unapologetically AuDHD 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 Patricia's website, podcast episodes and more: www.unapologeticallysensitive.com PODCAST GUEST B Lourenco, MA, LMHC (she/her) is a licensed mental health counselor, educator, advocate, and activist. B has been working in community support for nearly 20 years and is committed to social change on all system levels. Seeing mental health advocacy as a way to serve the community, she earned a Master of Arts degree in Clinical Psychology, with a Systems Emphasis, in 2015 and began her private practice, B Lourenco Therapy in 2017. B has also worked in the public school system, providing support to students with behavioral issues that made attending school challenging for them. Highly trained in Applied Behavior Analysis (ABA), B became a district-wide expert in supporting neurodivergent students. It was during this work that she began to be critical of the medical models of support for neurodivergence, including ABA. Making the shift from the medical to the Neurodiversity-affirming model has allowed her to finally identify her own neurodivergence, including Autism and ADHD. Combining her lived experience of neurodivergence, along with years of anti-oppression work, B is passionate about helping others untangle themselves from harmful practices and align themselves with those that instead support marginalized communities. In addition to CE events for healthcare providers, she has also been a speaker on panels and podcasts, and also facilitates community based workshops. https://www.blourencotherapy.com LINKS Cascadia Training: https://cascadia-training.com Imani Barbarin—crutches_and_spice IG https://www.instagram.com/crutches_and_spice/ 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 Unapologetically AuDHD Podcast-- https://unapologeticallysensitive.com/unapologeticallyaudhd/ e-mail-- unapologeticallysensitive@gmail.com Show hashtag--#unapologeticallysensitive Music-- Gravel Dance by Andy Robinson www.andyrobinson.com

I've had so many jobs over the years — from babysitter to office administrator — and I didn't know until much later that my struggles in certain environments were connected to being autistic. In this episode, I talk about what it means to navigate workplaces that aren't built for neurodivergent minds, and how universal design could change everything. This is about moving from just "accommodating" us to truly including us.Watch this episode on YouTube.If you'd like to know more about topics discussed in this episode, check out:"Workplace Accommodations and Neurodiversity" by Susanne Bruyère and Adrienne Colella (chapter in Neurodiversity and Work: Employment, Identity, and Support Networks for Neurominorities edited by Eric Patton and Alecia Santuzzi)"Accommodations vs Universal Design" by CultureAlly"Autistic Adults' Views and Experiences of Requesting and Receiving Workplace Adjustments in the UK" by Jade Davies et al.Universal Design: Creating Inclusive Environments by Edward Steinfeld and Jordana Maisel"How Can the Work Environment Be Redesigned to Enhance the Well-Being of Individuals With Autism?" by Michał Tomczak"Autism and the Right to a Hypersensitivity-Friendly Workspace" by Bouke de Vries"'It's Like a Ramp for a Person in a Wheelchair': Workplace Accessibility for Employees With Autism" by Michal Waisman-Nitzan et al.  Theme music: "Everything Feels New" by Evgeny Bardyuzha. All episodes written and produced by Kristen Hovet.Send in your questions or thoughts via audio or video recording for a chance to be featured on the show! Email your audio or video clips to otherautism@gmail.com through WeTransfer. Buy me a coffee!Buy The Other Autism merch. Use code FREESHIP for free shipping on orders over $75 USD! The views, opinions, and experiences shared by guests on this podcast are their own and do not necessarily reflect those of the host or production team. The content is intended for informational purposes only and should not be taken as medical or professional advice. Please consult with a qualified healthcare provider before making any decisions related to your health, fitness, or wellness.

In this episode, Hailey shares a few cozy county escapes across Wisconsin! As summer fades and Wisconsin's landscapes shift into shades of gold and red, it's the perfect time to sneak away. Dreaming of mornings on the lake, nights under the stars, or waking up to the sound of farm animals? Every corner of Wisconsin has a stay perfect for you! From treetop hideaways to historic inns, here are a few handpicked spots where fall feels extra special.The Bobber is brought to you by Something Special from Wisconsin: https://www.somethingspecialwi.com/Read the blog here: https://discoverwisconsin.com/cozy-county-escapes-september-stays-across-wisconsin/Bayfield County: https://www.wicounties.org/counties/bayfield-county/; BoulderRidge Tree House: https://www.bayfield.org/listing/boulderridge-tree-house/409/; Lake Superior Sea Caves: https://www.nps.gov/apis/learn/nature/caves.htm; Apple Hill Orchard: https://www.applehillorchard.com/; Hillcrest Orchards: http://www.hillcrestorchards.net/; Bayfield Apple Festival: https://www.bayfield.org/bayfield-apple-festival/; La Crosse County:https://www.wicounties.org/counties/la-crosse-county/; Rainbow Ridge Farms: https://www.rainbowridgefarms.com/; Brown County: https://www.wicounties.org/counties/brown-county/; The Astor House Bed & Breakfast: https://astorhouse.com/; Lambeau Field: https://www.packers.com/lambeau-field/; Fox River State Trail: https://dnr.wisconsin.gov/topic/parks/foxriver; LoCo WisCo: https://www.locowisco.com/; Bhava Coffee: https://www.bhavacoffee.com/; Walworth County: https://www.wicounties.org/counties/walworth-county/; Lake Geneva Lodge: https://genevalakelodge.com/; Geneva Lake Shore Path: https://www.visitlakegeneva.com/things-to-do/shore-path/; Lake Geneva Cruise Line: https://www.cruiselakegeneva.com/; Geneva Lakes Antique and Classic Boat Show: https://www.genevalakesboatshow.com/; Pier 290: https://pier290.com/The Bobber: https://discoverwisconsin.com/the-bobber-blog/The Cabin Podcast: https://the-cabin.simplecast.com. Follow on social @thecabinpodShop Discover Wisconsin: shop.discoverwisconsin.com. Follow on social @shopdiscoverwisconsinDiscover Wisconsin: https://discoverwisconsin.com/. Follow on social @discoverwisconsinDiscover Mediaworks: https://discovermediaworks.com/. Follow on social @discovermediaworksWisconsin Counties Association: https://www.wicounties.org/

For this episode of the show, we are joined by Amy Cushner! Amy has dedicated more than 30 years to the Shelton School and a lifetime to advocating for neurodivergent individuals, infusing passion, humor, and wisdom into every stage she graces. From classrooms in Dallas to conferences in China, she has become a sought-after voice championing inclusive, strengths-based approaches across both education and business.. In this episode, Amy breaks down the important differences between accommodations, modifications, and remediation in the education system, explaining how these terms are often used interchangeably but have distinct purposes that can significantly impact a child's learning journey. Amy discusses the historical context, which traces back to Thomas Jefferson's vision for public education and the challenges of the "Goldilocks effect," ensuring the right fit for every student. She highlights why it's so important to understand the “magic number” that determines when remediation is provided, highlighting that the need for support does not disappear just because a student falls short of the threshold. Amy stresses the importance of understanding important distinctions as they have major implications for a student's educational journey, particularly when it comes to college and career choices, and she also emphasizes the crucial role of early intervention and the empowerment of students to self-advocate, using visual cues and clear communication about their accommodations. Throughout our conversation, Amy shares some valuable insights and practical advice for parents and educators, highlighting the need for a collaborative approach and the recognition that every child's learning journey is unique.  Show Notes: [3:21] - Amy Cushner traces public education's evolution from Jefferson to modern challenges in individualized learning. [6:54] - Students often get accommodations when remediation or intervention is truly required. [7:12] - Amy criticizes rigid “magic number” cutoffs for remediation, calling them unfair and financially motivated. [9:13] - Accommodations, Amy explains, provide classroom access without altering expectations or content. [11:18] - Amy contrasts accommodations with modifications, which lower expectations to match processing or cognitive challenges. [13:54] - Amy highlights knowing accommodation vs. modification and likens it to learning another country's customs. [15:12] - Remediation can help develop missing skills caused by neurological learning differences, not intellectual deficits. [17:31] - Research shows us that remediation builds entirely new neural pathways, effectively rewiring students' brains. [20:17] - When schools won't fund remediation, parents have to seek external diagnoses and licensed therapists. [23:19] - Hear how true remediation requires trained therapists. [26:45] - Remediation needs to be paired with accommodations like audiobooks for full access. [27:39] - Amy explains how modifications alter curriculum expectations, influencing future school and college options. [30:02] - Amy suggests that teachers can use accommodations across the board to help build learning from the ground up. [32:32] - Starting instruction too high frustrates students, while accommodations let them build confidence gradually. [34:59] - Educational advocates help parents navigate laws, testing, and school obligations, helping to ease parental burdens. [38:10] - Timely intervention prevents years of lost learning caused by eligibility cutoffs. [41:21] - Amy encourages early remediation and teaching children to self-advocate for their accommodations. [44:29] - Honest conversations can help kids avoid developing inaccurate, damaging narratives about struggles. [45:48] - Amy reframes nonstandard brains as strengths that offer unique ways of seeing the world. [47:02] - What is the best way to get in touch with Amy Cushner? Links and Related Resources: “How to Initiate a Special Education Assessment” Episode 109: “IEP and 504 Plan Q&A with Vickie Brett and Amanda Selogie” Episode 164: “5 Keys to Productive IEPs with April Rehrig” Episode 218: “Understanding IEPs and 504 Plans: Which One Is Right for Your Child? - Marisol Chianello”   Connect with Us: Get on our Email List Book a Consultation Get Support and Connect with a ChildNEXUS Provider Register for Our “When Struggles Overlap” Live Webinar Email Dr. Wilson: drkiwilson@childnexus.com    Connect with Amy Cushner: Amy's LinkedIn Page Phone: 972-855-8949 Email: amy@aceservice.org   

In this episode of Ogletree Deakins' Litigation Lens podcast series, shareholders Michael Nail (Greenville) and Fiona Ong (Baltimore) dissect a Seventh Circuit Court of Appeals case concerning an accommodation request brought under the Rehabilitation Act. The speakers explain why the Seventh Circuit found the employer's alternative accommodation reasonable in a case involving a VA hospital employee's request for parking and scooter storage amid COVID-19-related entrance changes. Michael and Fiona—emphasize that accommodations must be effective, not perfect—and cover the interactive process, changing accommodations without proving undue hardship, and damages considerations.

Frommer's Author David McElhenny joined Pauline Frommer to discuss the culinary specialties of different Japanese regions, walking vacation opportunities that mirror the Camino de Santiago experience, ways to experience Japan's sizzling pop culture, and some strategies for saving money on a Japanese vacation.Takeaways:Transportation in country is one of the highest costs travelers face, but buying a Japan Rail Pass may save you money. A look at its pros and cons.Accommodations can also take a bite out of the budget, so we discussed what capsule hotels are like, plus the more conventional but still affordable options most travelers prefer. Japan's culinary offerings are diverse and budget-friendly. We took a look at convenience store meals, Tokyo's Ramen scene, and the foods eaten in a region of Japan that has the most centenarians. Visiting off-the-beaten path Japan will get you out into some stunning nature areas, and into communities that really need the tourist business.The Frommer's Travel Podcast was named one of the 13 best for travel by the New York Times. It is hosted by Pauline Frommer, the Publisher of the Frommer's guidebooks and Frommers.com, with new episodes issued weekly.Mentioned in this episode:Check out the Smart Travel PodcastThis week's show is supported by the new Smart Travel Podcast. Travel smarter — and spend less — with help from NerdWallet. Check out Smart Travel at the Link below:Smart Travel Podcast

Interviewees: Matthew Sullivan, PhD, Assistant Director of Disability Resources, Washington University School of Medicine in St. Louis Suchita “Suchi” Rastogi, PhD. MPH Candidate, University of Illinois Chicago; CEO, Disability in Medicine Mutual Mentorship Program Interviewer: Lisa Meeks, PhD, MA, Guest Editor, Academic Medicine Supplement on Disability Inclusion in Undergraduate Medical Education Description: In this episode of Stories Behind the Science, Dr. Lisa Meeks talks with Matt Sullivan (Washington University School of Medicine) and Suchita “Suchi” Rastogi (UIC; DM3P) about their paper, “Standardized Language for Clinical Accommodations in U.S. Undergraduate Medical Training: Results From a National Modified Delphi Consensus Study,”part of the Academic Medicine supplement on Disability Inclusion in UME. Their conversation explores how a grassroots idea—born from students' lived experiences and practitioners' urgent need for clarity—grew into the first national, evidence-based language guide for clinical accommodations. Together, they unpack how a modified Delphi process brought students, Disability Resource Professionals, and leaders together to build consensus around the precise language that transforms intention into implementation. The trio discuss how language and word choices can make the difference between support and confusion, and how transparent, shared language strengthens trust and access for all. Dr. Meeks, Sullivan, and Rastogi also reflect on the collaborative model that made this project possible—one that centers disabled voices, encourages vulnerability in leadership, and demonstrates how clarity in communication is the foundation of equity. Listeners will come away with practical takeaways for institutions and leaders: audit your accommodation templates, build structured partnerships between DRPs and Student Affairs, and engage students as co-creators in designing accessible clinical environments. Transcript: https://docs.google.com/document/d/1ooJ5TP8V8s4t35EECoWHNTta7qqwbKlx-Fgu_WIiPG4/edit?usp=sharing Bios: Matt Sullivan PhD Dr. Sullivan is the Assistant Director of Disability Resources, At Washington University in St. Louis, and serves as DR's liaison to WashU's School of Medicine, acting as the primary contact for SoM faculty/staff, students, and prospective students.  In this role, Matt works closely with all parties to create an accessible and inclusive educational environment for disabled students pursuing their degrees within Health Sciences and Medicine. Dr. Sullivan is a research-oriented practitioner dedicated to promoting disability awareness and inclusion within the higher education environment.  In his student affairs roles, Dr. Sullivan has experience providing leadership and direction for a variety of programs and services in the areas of disability, testing, tutoring, Supplemental Instruction, and academic coaching.  Working in the field of disability services for more than a decade, Matt has dedicated his time and energy to the education and development of students, faculty, and staff surrounding the intersectionality of disability with race, culture, gender, and other prominent identity factors. Suchita “Suchi” Rastogi PhD Suchi is an MPH student at the University of Illinois Chicago and CEO of the Disability in Medicine Mutual Mentorship Program (DM3P). A former MD-PhD student at Stanford University, she advocates for accessible medical education and leads community-based efforts to promote disability inclusion and peer mentorship. As a South Asian disability activist, she values health equity and compassionately designed systems that serve all people with dignity. She believes everyone deserves respect, access to material resources, and psychosocial support. These values compel her to improve healthcare and public health infrastructure for disabled patients, increase disability representation in medicine, and shift attitudes towards persons with disability. To accomplish this, she 1) run a mentorship program (DM3P) for healthcare professionals with disability, 2) conducts disability health equity research, and 3) advocates for evidence-based policies that center accessibility. Key Words: Clinical accommodations · Disability inclusion · Medical students · Disability Resource Professionals ADA Resources: Article from Today's Talk: Dhanani Z, Rastogi S, Sullivan M, Betchkal R, Poullos P, Meeks LM. Standardized Language for Clinical Accommodations in U.S. Undergraduate Medical Training: Results From a National Modified Delphi Consensus Study.Academic Medicine. 2025;100(10S):S92–S97. DOI: 10.1097/ACM.0000000000006150 Read the full article here → Equal Access for Students with Disabilities: The Guide for Health Science and Professional Education (2nd Ed). Meeks LM, Jain NR, & Laird EP. Springer Publishing, 2020. Read here → The Docs With Disabilities Podcast: https://www.docswithdisabilities.org/docswithpodcast

This week, Dave welcomes back his good friend Jeff Copper of DIG Coaching for a vital discussion tailored for the busy professional navigating life with ADHD. Many with ADHD excel at problem-solving for others, but often struggle to implement those same solutions for themselves. This episode dives into the concept of executive function impairment and introduces a new approach. Jeff shares how this model provides a simple, actionable, and universal accommodation to help mitigate the challenges of ADHD and burnout. Tune in to understand why direct communication is the most basic, yet often overlooked, tool for achieving clarity with Adult ADHD. Key Discussion Points ADHD and Problem Solving: Individuals with ADHD are often excellent problem solvers and "connect the dots" better than others, but struggle to apply these skills to their own lives. The Role of Executive Functions: ADHD is defined as an executive function impairment, meaning the "mind tools" used for problem-solving (planning, organizing, decision-making) are less efficient, requiring much greater effort in some cases. Strategies vs. Execution: Having a plan or strategy isn't enough; the difficulty lies in the execution which requires intensive use of executive functions. Cognitive Ergonomics from the Inside Out: Jeff Copper's model posits that direct communication (talking things through in real-time) is a universal accommodation for ADHD. Communication as an Accommodation: Language evolved to solve shared problems, making direct, collaborative conversation the most fundamental form of problem-solving. People with ADHD simply need this accommodation more. The Power of Clarity: The majority of procrastination is rooted in ambiguity, which direct communication is designed to resolve. **Do you want to work with Dave one-on-one? Go to www.overcomingdistractions.com and book an introductory Zoom chat. Or go directly to Dave's calendar; https://calendly.com/davidgreenwood1/15min  

As tensions arise between the US and China over critical minerals, could Australia be the key player to reshape the balance? Private credit under the microscope as investors dive in, and regulators ponder what to do next. Women seek better understanding around menopause in the office. Gold price defies gravity again. And the ASX wipes off all the gains it made towards records. Interviews with: Robert Makdissi, Investment Manager at Akambo & Kathryn Carter, MyPause Health founder Email us your thoughts to moneynews@nine.com.au Hosted by: Tom StoreySee omnystudio.com/listener for privacy information.

Dr. Monty Pal and Dr. Fumiko Chino discuss several of the top abstracts presented at the 2025 ASCO Quality Care Symposium, including research on federally funded clinical trials and financial reimbursement for trial participation. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I am your host, Dr. Monty Pal. I am a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, we are highlighting key abstracts that were presented at the 2025 ASCO Quality Care Symposium. I am delighted to be joined today by the chair of this year's meeting, Dr. Fumiko Chino. Dr. Chino is an associate professor in radiation oncology at MD Anderson Cancer Center with a research focus on access, affordability, and equity. She is also a consultant editor of JCO Oncology Practice and the host of the Put into Practice podcast. I have got to listen to that.  Dr. Chino, welcome, and thanks so much for being on the podcast today. Dr. Fumiko Chino: I am overjoyed to be here, and absolutely, you should take a listen. Dr. Monty Pal: Definitely. And FYI for listeners, our full disclosures are all available in the transcript of this episode, so do have a look if you are inclined. Now, we have really seen some fantastic advances in health services and quality and supportive care, digital health, and beyond. There are some great abstracts that were presented at this year's meeting. I have actually picked a couple that I am particularly interested in and that I believe you share my interest in as well.  So, the first is an abstract actually from my friends at SWOG (Abstract 94). So, this was a terrific abstract from Joe Unger and Michael LeBlanc and Dawn Hershman. And this, I think, really hits on a very, very key issue right now, which is the benefit of federally funded trials. Do you mind just kind of spelling out some of the observations from what I think is a really brilliant piece of work? Dr. Fumiko Chino: Absolutely, and I think Dr. Unger's work is really important for our current funding environment. I think that this research is really essential to do to show the role of federal sponsorship in the design and conduct of clinical trials. Because what they did was really look at a landscape analysis over the last 20 years looking at funding and were able to show quite clearly that federal funding really matters for advancing the science in cancer care. So what they showed was that the federal funding was more commonly essential for early-stage clinical trials, so those phase 1, phase 2 trials that really help advance the science. And that federal funding was really essential for multimodality drug combinations, combinations with drug and surgery, combinations with drug and radiation. Those trials were much more likely to be federal funded. And then the last thing is that they showed that the patients that are, I think, the largest at risk for gaps in care who really need the advancements in science that keep U.S. health care amazing and wonderful and world-leading, so the kids, the pediatric patients, the patients with rare cancers, and the patients actually that could benefit from de-escalation or right-sizing of treatment, they were also all more likely to have federal funding. So I think this research that was presented really shows that if, unfortunately, current status of restricted federal funding continues, that we are going to lose out in terms of the next generation of cancer cures, cancer de-escalations, and the type of combination treatments that make advancements in science. Dr. Monty Pal: Indeed. You know, I always point to Joe Unger's paper, and I think it is in JAMA Oncology, right, that showed life-years gained from NCI trials. It is such an important piece of work. I think this is a really nice complement to that, isn't it, to show the specific areas that otherwise would be, am I right in saying, kind of largely untouched? Dr. Fumiko Chino: I think you are right in that what we know from what industry will sponsor versus what the federal government will sponsor, that the federal government really helps make up the gap to really make those advancements that save lives, that lead to more birthdays, that advance our knowledge and our capacity for providing more cures and more successful futures for our patients. I always like pointing to the de-escalation research, which is, and this is not to dig pharma, but no pharmaceutical company is going to run a trial that says you can give less of their drug, right? It just does not make sense for the business end of the science. And so, thinking about how to right-size treatments, how to do more with less, that really is the purview of the federal government. Dr. Monty Pal: Absolutely. Absolutely.  I am going to shift gears here and bring up another abstract that I found to be quite intriguing, and this relates to reimbursement of expenses, et cetera, for clinical trials. This is an abstract from Courtney Williams and team. It brings to mind the importance, I think, of recognizing the hardships that patients take on by clinical trials, but I also would love for you to comment on that sort of fine line between reimbursement for expenses and then, you know, sort of undue enticement. It is a challenging balance there. But give me your reflections on this abstract. Dr. Fumiko Chino: Absolutely. You are speaking about Dr. Williams' Abstract 93 from the Alabama group, and Alabama actually has this incredible group of health services researchers which is, are doing really important work in this space. What this trial shows is that, you know, it is a small pilot study, it is 30-something patients that received some support primarily for their travel and additional expenses related to their clinical trial participation for breast cancer. It showed that the money helps, and I think what we all know is that it is expensive to participate in clinical trials. It requires additional visits. It often requires some significant travel burden for our patients, and I do not feel that money reimbursement for clinical trial expenses is an inducement. Nobody participates in a clinical trial to get the money for their gas, right? We know that our patients are making some pretty significant sacrifices in order to participate in clinical trials, and what this type of program does is just actually reimburse them for their outlaying of funds.  And I loved this trial because the patients were actually given $1,000 a month for the first 4 months of their trial participation, and what the study showed is that the patients were using it for things like travel-related food, for things like transportation, caregiver expenses, or even some of their out-of-pocket medical expenses like cost sharing or prescriptions. And that they said that overall, the reimbursement really made a difference in terms of their capacity for staying on the clinical trial. Because we know our clinical trials really are not able to enroll the full diversity of patients that often have a disease, and that the patients that are at biggest risk for a health care disparity or a gap in care are also the least likely to enroll in a clinical trial.  Programs like this are an essential part of showing how financial toxicity can be overcome with pretty straightforward assistance to patients to help reimburse them for the things that they are already taking out of their pocket, for parking costs, for that $10 soup that they buy at the cancer center, for those additional expenses that we are, unfortunately, putting on them. Dr. Monty Pal: Very well said. And you know, I have started to dabble in clinical trials looking at CAR T-cell therapies for kidney cancer, and I have to tell you, it is just insane the amount of cost that a patient would have to take on to comply with the stipulations for some of these novel therapies. We require that they stay within 30 minutes of the facility for 28 days, and unless we are compensating for some of that, I mean, how can one afford a hotel stay that is that long? I mean, it is just, it is unprecedented, and it would certainly provide a huge barrier to many patients who would otherwise enroll. Really well said. I also wanted to bring up another financially driven topic, and treating renal cell, again, I would say the vast majority, 90% plus of my patients in clinic are on oral drug therapies. And I cannot tell you how often a patient will show up in my practice and say, "Doc, I have got 15 days out of this 30-day prescription left. What do I do with it?" You know, or some come with pill bottles from a deceased loved one. And it is so frustrating to say, "Take it to the pharmacy and they will just get rid of it for you." But sounds like there is an abstract from Dr. Mackler, Abstract 102, that seems to address this topic quite well. Am I right? Dr. Fumiko Chino: Absolutely. This presentation, I was the most excited about seeing because this group, which helps run a cancer drug repository, theirs is called YesRx, presented their data from the last approximately two years of running this repository, and they were able to show incredible benefit for their patients in Michigan. And it is a really straightforward program. It is run by pharmacists. It has support from the legislation in Michigan. And what they were able to show is that they repurposed medications that would otherwise have been discarded. They delivered them directly to the oncologist, which then actually dispersed them to the patients. They helped 1,000 patients in less than two years. They saved them millions of dollars, over $15 million presented in the abstract. And it is just a win-win-win because I know that patients actually, and sometimes patient caregivers, they feel very sad to have spent a lot of money out of pocket for their medication, and then if they have a dose reduction or, obviously, you know, if the surviving spouse then has to get rid of their medication, just dispose of them, it is very disheartening. And this is a way of kind of reclaiming power for patients. So they were able to accept donations from all over the state of Michigan and then also help over 1,000 patients. And so, it is a phenomenal program. Dr. Monty Pal: Just wild when I came across the dollar amounts, right, that they were saving. It just, it seems like a place that, you know, we just have to look, as cancer centers, right, and really take this on. Just brilliant. On that same theme of cost savings and so forth, you know, I think there has been a lot of focus on what recent policies have done in the context of us having access to therapies and so forth. And one of the topics that has come up is the Inflation Reduction Act and how changes pertaining to the IRA have really played a role in one's ability to take on some of these expensive prescriptions. And I believe John Lin and colleagues tackled that issue in Abstract 97. Could you comment on that, Fumiko? Dr. Fumiko Chino: Absolutely. Dr. Lin is one of my colleagues here at MD Anderson, so I know him very well, and he has been doing really phenomenal work over the last several years with looking at drug affordability and access. And what his analysis shows is that for patients, after the Inflation Reduction Act's cap on out-of-pocket expenses, is that it really did show that out-of-pocket expenses decreased. So what the Inflation Reduction Act did is that it eliminated the 5% co-insurance and placed this $2,000 cap on out-of-pocket expenses. And what that led to for these patients that were not able to have the low-income subsidy is that there were lower costs, and that there was a lower rate of drug abandonment, meaning that the prescription was not refilled. There was also a lower rate of unfilled prescriptions as well. And I think that it shows that health policy really can improve access to care. I think the flip side of the fact that the IRA, this policy, really did seem to help people is that what his research showed is that actually, even with the benefits of this cap, is that actually it is still really high in terms of the rate of people who are not able to fill their prescriptions or that completely abandon them over time. And that unfortunately, even with this change, that over half of people without the low-income subsidy were potentially not getting the full benefit of their medications because they were not able to afford them. And so I think it really kind of highlights that we still need to do more work about making drugs affordable. Dr. Monty Pal: Indeed, indeed. And I mean, in a setting like this, I mean, I think it is important to recognize that $2,000 is a lot, it is a big chunk of change, right, for a lot of families in the U.S. What do you think of the prospect of, like, decreasing that cap? Is that something that from a policy standpoint you would be supportive of? Dr. Fumiko Chino: Well, so something that is a real option for patients on Medicare is there is something called the Medicare Prescription Payment Plan, and what it allows you to do is actually prorate the $2,000 over the whole year. And so instead of having to pay $2,000 as soon as you fill your prescription, because you are going to have, if you have an expensive medication, it is essentially you have to pay the $2,000 in January, right? It allows you to prorate it, so essentially $170 a month, and that comes to you as like a regular bill. And I think that as rolled out as part of the IRA is a really lovely way of thinking about how do we make these payments more stable over time, so it is not a huge hit sort of at the beginning of the year. And I think that alone actually can make a difference in terms of trying to help make sure that people can actually get their medications. Dr. Monty Pal: That is an excellent tip. Excellent tip.  We are going to shift gears entirely. We have been talking a lot about the dollars and cents of things and talk about an abstract from Sophia Smith and colleagues. So this is Abstract 550 at your meeting. And this hinged on a program of sorts to deal with post-traumatic stress disorder. We do not often think about PTSD in the vernacular for oncology patients, but indeed, I mean, it is something that they must face, especially in the context of long-term survivorship. Can you talk a little bit about Dr. Smith's abstract? Dr. Fumiko Chino: Absolutely. I love this work from Dr. Smith, who is at Duke. She worked with Dr. Applebaum, who was my old colleague at Memorial Sloan Kettering. And this group of researchers really is trying to figure out how to best support people into survivorship so that they can actually thrive. And their patient population for this work was actually people who received stem cell transplant, and they focused on people who had PTSD symptoms. And what they were able to show through this SMART design, which is essentially this serial, multiple randomized trial, so everyone got randomized upfront to either usual care or this app, so this digital app that actually helped coach people through cancer distress. And then for the people who were non-responders, they were then additionally randomized to either the app plus coaching or a therapist versus the cognitive behavioral therapy or CBT.  And what they were able to show is that, number one, anyone who had the app seemed like they did better than those who did not start the path with the app. But then the additional help of either the therapist or the coach or the CBT made additional benefit over time. And so, I think this shows a really nice stepped care, which is you can potentially have some right-sizing of treatments cost saving, if we sort of give everyone the app, which is, I think, overall pretty low cost. And that for the people who do not get the full benefit from the app, then you can think about these maybe more tailored approaches, the therapist, the coach, the CBT, but that some people actually just respond to the app. And I think it allows us to, again, right-size the care for our patients. And I think it is really innovative to think about how technology can help improve access to care in the setting of something like PTSD. Dr. Monty Pal: Brilliant summary. Brilliant summary.  Gosh, it looks like such an exciting meeting this year. Congratulations on a terrific program for the ASCO Quality Care Symposium. I know you played a huge role in developing it, and thanks for sharing your insights on the ASCO Daily News Podcast. Dr. Fumiko Chino: No, I really appreciate you having me. ASCO Quality is my favorite meeting of the year. You know, it is really a phenomenal meeting, and I am so excited for next year in Boston in 2026. Dr. Monty Pal: Awesome. And thanks to our listeners too. You are going to find links to all the abstracts that we discussed today in the transcript of this episode. Finally, 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. 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. Sumanta (Monty) Pal  @montypal Dr. Fumiko Chino @fumikochino Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures of Potential Conflicts of Interest: Dr. 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. Fumiko Chino:  Consulting or Advisory Role: Institute for Value Based Medicine Research Funding: Merck

On this episode of The Steve Dangle Podcast, 00:00 Leafs beat the Preds 54:45 A great Ducks giveaway 1:02:30 Rangers lose at home again 1:11:00 The Sharks owner speaks 1:25:30 A Sharks giveaway 1:28:00 Adam's Pittsburgh fat guy corner 1:42:00 Accommodations for NHLers at the Olympics Donate to Steve's Easter Seals page: https://eastersealsontario.akaraisin.com/ui/lindros2025/p/078df4e3c0c444d59a551259d78a749e Donate to Adam's Easter Seals page: https://eastersealsontario.akaraisin.com/ui/lindros2025/p/12938347f56e4b2eab06c3a423a727f6 Donate to Jesse's Easter Seals page: https://eastersealsontario.akaraisin.com/ui/lindros2025/p/f58403a20caa4b47a17e19cf86c198d9 Visit this episode's sponsors: Grab a pack today.  Visit your local Tim Hortons, or download the Tims App, to start collecting Tim Horton's NHL Hockey Trading Cards. Grab your EXCLUSIVE NordVPN Deal by going to https://nordvpn.com/dangle to get a Huge Discount off your NordVPN Plan + 4 additional months on top! It's completely risk-free with Nord's 30-day money-back guarantee! Hope in Every Step is more than a walk — it's a movement. Held this year at Spencer Smith Park in Burlington on November 1st, the event brings our community together to stand against gender-based violence. Visit https://hope-in-every-step.raiselysite.com/donate for more information. Join us at The Rec Room: https://sdpn.ticketspice.com/sdp-x-the-rec-room Join Drew & Stew Pick Em' ➡️ https://app.sparc.fun/point-spread/dspe Check out https://sdpn.ca/events to see The Steve Dangle Podcast live! Subscribe to the sdpn YouTube Channel: https://www.youtube.com/@sdpn?sub_confirmation=1Join - SDP VIP: YouTube: https://www.youtube.com/channel/UC0a0z05HiddEn7k6OGnDprg/join Apple Podcasts: https://apple.co/thestevedanglepodcast Spotify: https://podcasters.spotify.com/pod/show/sdpvip/subscribe - Follow us on Twitter: @Steve_Dangle, @AdamWylde, & @JesseBlake Follow us on Instagram: @SteveDangle, @AdamWylde, & @Jesse.BlakeJoin us on Discord: https://discord.com/invite/MtTmw9rrz7 For general inquiries email: info@sdpn.ca Reach out to https://www.sdpn.ca/sales to connect with our sales team and discuss the opportunity to integrate your brand within our content! Learn more about your ad choices. Visit megaphone.fm/adchoices

In this week's episode of Special Education for Beginners, we're continuing our October series all about writing IEPs that are clear, meaningful, and truly connected.So far this month, we've talked about how your Present Levels (PLAAFPs) act as the blueprint of the IEP and how to use that information to write strong, measurable goals. Now we're moving one step further — connecting those goals to the services, accommodations, and supports that make them work in practice.If you've ever caught yourself copying last year's IEP just to “save time,” you're not alone. But today, we're hitting reset and walking through five simple steps to make sure every service and accommodation in your IEP is backed by data and directly connected to your student's current needs.In this episode, you'll learn:✅ How to use data from the Present Levels to guide your decisions✅ What questions to ask yourself before adding or adjusting services✅ How to ensure every support ties back to an IEP goal✅ Why alignment matters for both compliance and student success✅ Tips for knowing when it's time to remove outdated accommodations or servicesPlus, I'm sharing how AI tools can actually help you pull out student strengths and needs more efficiently — without replacing your professional judgment. If you want to try this for yourself, check out my resource Using AI to Write IEPs: Identifying Strengths and Needs, which walks you step-by-step through how to use AI responsibly to analyze data and identify key areas for growth. And if you're looking for more support with goal writing, my IEP Goal and PLAAFP Forms are designed to simplify the process while keeping your writing precise, professional, and personalized.

Accommodating neurodiversity doesn't have to mean resentment or burnout. In this episode, we explore how a neurodiverse relationship can thrive when both partners learn to balance self-accommodation and mutual respect. Coaches Jeremy & Charity Rochford show how neurodivergent partners can self-accommodate (not outsource to neurotypical spouses) and how neurotypical partners can set boundaries that protect their own bandwidth. You'll learn concrete tools—transition buffers, noise strategies, visual timers—and how a shared relationship system replaces score-keeping with reciprocity. If you've been told to “just run” from a neurodiverse relationship, this episode offers a smarter path. Jeremy (autistic) & Charity (neurotypical) (hosts of the NeuroFam podcast) join Jodi to show how reframing autism/ADHD from problem to predictable pattern unlocks real solutions. We dig into practical rituals that improve connection without enmeshment, plus we explore why “effort is invisible” and how accommodations can increase connection instead of being sacrifices for either partner. Jeremy explains his “software upgrade” mindset (strengthening theory of mind/executive function like training a muscle), while Charity shares how compassion + structure reduce resentment. You'll leave with scripts, rituals, and a way to accommodate needs without erasing yourself. 00:00 – Welcome to Season Five 01:00 – Meet Jeremy & Charity 04:45 – Autism isn't the problem: Updating the ‘80s narrative 09:40 – How kid diagnoses led to adult discoveries (and relief) 14:20 – Compassion shifts: Seeing sensory overload vs. “too much” 18:30 – “Software upgrades”: Building empathy & executive function 22:10 – Accommodations that work: Earbuds, car rules, visual timers 29:10 – Resentment vs reciprocity: Why effort is invisible 33:00 – Build a marriage system: Make expectations explicit 35:20 – Accommodate without erasing yourself (Disney example)

Parents often rely on their usual parenting strategies to help their child with OCD — but those same strategies can actually backfire. In this episode, I break down the most common approaches parents try and explain why they don't work when it comes to OCD.If you've ever felt stuck, repeating the same things without progress, this episode will help you understand why and what to do differently.To get the PDF handout that supplements this episode go to www.natashadaniels.com/episode440✨ Get 50% off all my courses and workshops until December 18, 2025 11:59pm in honor of OCD Awareness Week. Go to AT Parenting Survival School and use the coupon code OCDAWARENESS2025.Links mentioned in podcast:Podcast: Validation vs Accommodations in OCDPodcast: Developing Effective Incentive PlansReel: Distraction vs Refocusing***This podcast episode is sponsored by NOCD. NOCD provides online OCD therapy in the US, UK, Australia and Canada. To schedule your free 15 minute consultation to see if NOCD is a right fit for you and your child, go tohttps://go.treatmyocd.com/at_parentingThis podcast is for informational purposes only and should not be used to replace the guidance of a qualified professional.Parents, do you need more support?

Thanks for joining me, Holly Blanc Moses - The Mom/Neurodivergent Therapist, on The Autism ADHD Podcast. Is a neurodivergent student in your life struggling at school?  You're not alone—and there ARE supports that actually work. In this episode, I'm breaking down 5 game-changing school accommodations based on what parents, therapists, and educators are searching for most: communication supports, sensory regulation, executive functioning help, and more. These aren't vague suggestions—they're real examples you can implement in the classroom, recommend in evaluations, or request in IEP and 504 meetings. These 5 supports help in the areas of communication, regulation, executive functioning, writing, social interaction and mental health!  Perfect For: Parents preparing for IEP or 504 meetings and advocating for your child's needs. Therapists identifying school supports that will help clients emotionally, socially and academically. Educators looking for practical classroom strategies that work.  

This week on the Power of Owning Your Career Podcast, host Simone Morris welcomes Charlotte Dales, co-founder and CEO of Inclusively, for a lively and insightful discussion on charting your own course and building inclusive workplaces. Charlotte shares her remarkable journey—from banking at Deutsche Bank to starting successful companies and sparking positive change after being inspired by her cousin's achievements. Tune in for actionable tips on handling rejection, planning bold career moves, leveraging technology for growth, and embracing a mindset that keeps you in the driver's seat—no matter where you're starting from. Episode Highlights & Timestamps: [00:00] Intro to Charlotte & Overview of Inclusively [00:03] Charlotte's early career aspirations and pivot to finance [00:07] If your career were a book—Charlotte's title & philosophy [00:08] The formula for owning your career: key ingredients and mindsets [00:10] Stories of rejection, resilience, and not taking no for an answer [00:17] Strategies for self-advocacy and pitching yourself [00:19] Game-changing career resources (including Blinkist & AI) [00:22] Realizing you're in the driver's seat: the London story [00:23] Charlotte's parting words on perseverance and choice [00:24] How to connect with Charlotte and Inclusively Learn More & Get Involved: Learn more about host Simone E. Morris: LinkedIn Apply or recommend a guest: Become a Guest on the Show Looking for career support from Simone? Visit 52 Tips for Owning Your Career Connect with Charlotte: Inclusively: Website Charlotte Dales on LinkedIn: LinkedIn Follow & Subscribe: Follow us on social @simonemorrisent for updates & success tips! Subscribe for more inspiring guests and actionable career episodes.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. 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. Hope Rugo  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

Beau Martonik heads to Nebraska for an early-season deer camp with Thomas & Nate Krick (Identical Draw), Ben Dettamanti (Shed Crazy), Joel Burham (Whitetail Fit), and Josh Ilderton (The Untamed). The crew dives into what makes deer camp special—camaraderie, laughs, and lessons learned along the way. From spider stick pranks and quicksand mishaps to scouting strategies and close encounters, this episode of the East Meets West Hunt podcast captures the spirit of chasing whitetails together. Topics: 00:00:00 - Intro 00:04:11 – Introductions 00:06:30 – The Idea Behind This Camp 00:11:13 – Ben's Whitetail Perspective 00:13:07 – Spider Stick Shenanigans 00:15:25 – The Food Sources Debate 00:21:05 – The Quicksand Experience 00:23:41 – The Last Stand 00:29:07 – Ben's Shed Tour 00:32:05 – Nate's Buck 00:51:03 – Guest Switch - Josh Ilderton and Joel Burham 00:55:21 – Camp Life and Accommodations 01:00:22 – Hunting Timber vs. Agriculture 01:15:31 – Evening Strategies 01:22:36 – Wrapping Up the Adventure Resources: Joel Burham (Whitetail Fit) - YouTube and IG Identical Draw - YouTube and IG The Untamed - YouTube and IG Shed Crazy - YouTube and IG Instagram:   ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@eastmeetswesthunt⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@beau.martonik⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Facebook:   ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠East Meets West Outdoors⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Shop Hunting Gear and Apparel: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.eastmeetswesthunt.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ YouTube: Beau Martonik - ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.youtube.com/channel/UCQJon93sYfu9HUMKpCMps3w⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Partner Discounts and Affiliate Links: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.eastmeetswesthunt.com/partners⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Amazon Influencer Page ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.amazon.com/shop/beau.martonik⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Monty Pal and Dr. Matteo Lambertini discuss a compelling global study on the clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers, the association of pre-diagnostic awareness of BRCA status with prognosis, and the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants. TRANSCRIPT Dr. Monty Pal: Well, hello everyone, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. Now, when we think about genetic testing, whether for patients diagnosed with breast cancer or for other family members of them, it seems to be widely underutilized. Today, we're going to be discussing a recently published study in the Journal of Clinical Oncology that reported on the clinical behavior of breast cancer and specifically young BRCA1 and BRCA2 carriers, and the association of pre-diagnostic awareness of BRCA status with prognosis. I thought this was just a fascinating piece, and I honestly couldn't wait to have this conversation. It's a really compelling paper that highlights the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants, and really the need for genetic counseling and testing to inform people about early detection that could lead to a better prognosis. I'm really delighted to welcome the study's lead author, Dr. Matteo Lambertini. He really needs no introduction. He's very well known in the breast cancer world for his amazing contributions to fertility in the context of breast cancer, to pregnancy in the context of breast cancer, and genetic testing. He's an associate professor at the University of Genova, and a breast cancer medical oncologist at the San Martino Polyclinic Hospital in Genova, Italy.  Dr. Lambertini, thank you so much for joining us today. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a great pleasure. Dr. Monty Pal: Oh, thanks. And just FYI, if you're listening in and you want to hear our disclosures, they're all listed at the transcript of this podcast.  So, I poured through this paper [Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status] yesterday, Dr. Lambertini, and first of all, congratulations on this study. This was a huge international multicenter effort, 4,752 patients. How did you pool all these patients with young breast cancer? Dr. Matteo Lambertini: Thanks a lot for the question. Yes, this was an effort made by several centers all over the world. The main idea behind the creation of this network that we have named as BRCA BCY Collaboration, was to get as many data as possible in a sort of niche patient population in the breast cancer field, meaning women diagnosed with breast cancer at the age of 40 years or younger, and all of them being BRCA carriers. We know that around, in the Western world, around 5% of breast cancer cases are being diagnosed under the age of 40 years, and among them around 10-15% are BRCA carriers. So, I would say it's a relatively rare patient population where we did not have a lot of evidence to support our choices in terms of counseling on treatment, prevention, and oncofertility as well. That was the idea behind the creation of this network that includes many centers. Dr. Monty Pal: Yeah. You know, what's so interesting about this is that you sort of draw this line between patients who have BRCA testing at the time of diagnosis and then BRCA testing earlier in their course and then leading to a diagnosis perhaps. And I think that's where really sort of the dichotomy in outcome sits. Can you maybe elaborate on this and tell us about timing of genetic testing in this study and what that meant ultimately in terms of prognosis? Dr. Matteo Lambertini: In this specific analysis from this large network, including almost 5,000 women with breast cancer diagnosed at the age of 40 years or younger and being a BRCA carrier, we looked specifically into the timing of genetic testing because this is a retrospective study and the criteria for inclusion are those that I have just mentioned, so diagnosis at a young age plus carrying germline BRCA pathogenic or likely pathogenic variant. In this analysis, we have looked into the time the patient has got the genetic testing and particular we focused on two populations: those that were diagnosed, knowing already to be a BRCA carrier, and those that got tested after being diagnosed with breast cancer. And the main findings from this analysis have been that knowing to be a BRCA carrier was associated with a lower stage at the time of diagnosis, meaning more T1 tumors, so a tumor less than 2 cm, more node-negative disease, and this translated into less aggressive treatment, so less often axillary dissection, less often use of chemotherapy and anthracycline-based chemotherapy. And even more importantly, we have seen a better overall survival for those patients that were diagnosed already knowing to be BRCA carriers as compared to those tested after breast cancer diagnosis. These results after adjusting for all the confounding, stage, treatment and so on, there was not significant anymore, meaning that it's not the timing of test per se that is probably leading to a better survival, but it is the fact that knowing to be a BRCA carrier would likely translate into having access to all the preventive measures that we have in this setting and this will translate into an overall survival benefit, so in terms of saving more lives in young BRCA carriers. Dr. Monty Pal: I think it's such an important point, and it's one that I think might sound implicit, right, but it needs to be proven, I think, through a study like this. You know, the fact that finding this early, identifying the mutation, doing enhanced screening, and so forth, is really going to lead to superior clinical outcomes. One of the things that I think many people puzzle over, including myself, is what to do? I personally occasionally will see BRCA altered patients in the context of prostate cancer. But that's a very different population of individuals, right? Typically older men. In young females with BRCA mutation, I guess there's a specific set of considerations around reproductive health. You'd already highlighted preventive strategies, but what sorts of things should we be talking about in the clinics once a patient's diagnosed and once perhaps their breast cancer diagnosis is established? Dr. Matteo Lambertini: Yes, exactly. Knowing to be a BRCA carrier has a lot of implications from prevention to treatment to survivorship issues including reproductive counseling. And this is important not only for the patient that has been diagnosed with breast cancer but also for all the family members that will get tested and maybe identify with this sort of genetic alteration before diagnosis of cancer. Why this is important is because we have access to very effective preventive measures, a few examples: MRI screening, which starts at a very young age and normally young women don't have an effective screening strategy outside the BRCA field. Also, primary preventive measures, for example, risk-reducing surgery. These women are known to have a high risk of breast cancer and high risk of ovarian cancer. So the guidelines are suggesting to undergo risk-reducing salpingo-oophorectomy at a young age, so 35 to 40 years in BRCA1 carrier, 40 to 45 years in BRCA2 carrier. And also risk-reducing mastectomy should be discussed because it is a very effective way to prevent the occurrence of breast cancer. And in some situations, including the setting that we are talking about, so young women with breast cancer, BRCA carrier, also risk-reducing mastectomy has shown to improve overall survival.  On the other side, once diagnosed with breast cancer, nowadays knowing to be or not a BRCA carrier can make a difference in terms of treatment. We have PARP inhibitors in the early setting, in the adjuvant setting as well as in the metastatic setting. And in terms of survivorship implication, one of the critical aspects for young women is the oncofertility care which is even more complicated when we talk about BRCA carriers that are women candidates for gynecological surgery at a very young age. So this sort of counseling is even more complicated. Dr. Monty Pal: One of the other things, and this is subtle in your paper and I hope you don't mind me bringing it up, is the difference between BRCA1 and BRCA2. It really got me thinking about that because there are differences in phenotype and manifestation. Do you mind just expanding on that a little bit for the audience because I think that's a really important reminder that you brought up in the discussion? Dr. Matteo Lambertini: The difference between BRCA1 and BRCA2 carriers has been known that there are different phenotypes of breast cancer that are more often diagnosed in these two different populations. Normally BRCA1 carriers have a higher likelihood to develop a triple negative breast cancer as compared to BRCA2 carriers, more likely to develop a hormone receptor-positive HER2-negative disease. In this study, again, a specific population of young women with breast cancer, we have seen the same findings, mostly triple negative disease in BRCA1 carrier, mostly luminal-like disease in BRCA2 carrier. But what's novel or interesting from this study is to look also at the age at the time of diagnosis of this disease. And particularly in BRCA1 carriers, we should be sort of more careful about diagnosis of breast cancer and also other primary tumors including ovarian cancer because the risk of developing these malignancies is higher even at a younger age as compared to BRCA2 carriers. And this has implications also in the primary and secondary prevention that we were talking about earlier. Dr. Monty Pal: Oh, interesting. I guess the fundamental question then from your paper becomes, how do we get at the right patients for screening for BRCA1 and BRCA2? And I realize our audience here is largely oncologists who are going to be listening to this podcast, oncology providers, MDs, nurses, etc. But maybe speak for a moment to the general practitioner. Are there things that, for instance, a general practitioner should be looking for to say, “Wait a minute, this patient's high risk, we should consider BRCA1, BRCA2 testing or germline screening”? Dr. Matteo Lambertini: Yes, it's a very important question for the breast cancer community. After the updated ASCO guideline, the counseling is way easier because right now the age cutoff goes up to 65 years, meaning that all the patients diagnosed with breast cancer below the age of 65 years should be tested these days. And then above the age of 65, there are different criteria like triple-negative disease or family history. From a general practitioner standpoint, it's of course a bit more difficult, but knowing particularly the family history of the person that they have in front will be crucial to know if there are cases of breast cancer diagnosed at a young age, maybe triple-negative cases, knowing cases of ovarian cancer in first-degree relatives or pancreatic cancer in first-degree relatives, and of course cases of prostate cancer as well. So, I would say probably mostly the family side will be important from a general practitioner perspective.  From an oncology one, the other point that I think is important to stress also based on the data that we have shown in this publication is that having a case of breast cancer known to carry a BRCA pathogenic or likely pathogenic variant. It means that all the people around this case should get tested and if found to be BRCA carrier and healthy carrier, these people should also undergo the primary and secondary prevention strategies because this is very critical also to improve their outcomes and try to avoid the developing of breast or ovarian cancer, but also in the case of diagnosis of this disease, a diagnosis at an earlier stage, as we have seen in this paper. Dr. Monty Pal: Brilliant. I'm going to diverge from our list of questions here and close by asking a question that I have at the top of my mind. You're very young. I know our podcast listeners can't see you, but you're very, very young. Dr. Matteo Lambertini: Thank you. Thank you for that. Not so young but yeah. Dr. Monty Pal: You have nearly 300 papers. Your H-index is 67. You've already made these seminal contributions, as I outlined it from the outset, regarding fertility, regarding use of GnRH analogs, regarding pregnancy and breast cancer. What are you studying now? What are you really excited about right now that you're doing that you think might potentially be practice changing? Give us a little teaser. Dr. Matteo Lambertini: Yeah. Thanks a lot, Dr. Pal. Receiving this compliment from you is fantastic. So, thanks a lot for that. From my side, in terms of my research, I've been interested in the field of breast cancer in young women since the start of my training. I've had very good mentors from Italy, from Europe, from the U.S. I'm still interested in this field, so I think we still have a lot to learn to try to improve the care of young women with breast cancer. For example, the oncofertility care, which is something I worked a lot over the past years. Now with all the new treatment options, there's a sort of new chapter of oncofertility counseling. So, what's the impact of immunotherapy? What's the impact of the new targeted agents?  More on the genetic aspects, now we know that there's not only BRCA1 or BRCA2. There are a lot of other different genes that may increase the risk of breast cancer and other malignancies. And also for these genes, we really don't have a lot of evidence to counsel women on prognosis, treatment, prevention strategy. So we need to learn way more for this special patient population that are quite rare, and so we really need a multicenter academic effort to try to give some evidence in this field. Dr. Monty Pal: Yeah. It's tough because these are rare circumstances, but, you know, I think that you've done really well to sort of define some collective experiences that I think really define therapy. I mean, I just remember when I was in training 25 years ago, just reading through textbooks where all the experience around breast cancer and pregnancy was really just very sort of anecdotal almost, you know? And so it's great to see that the state of the science has moved forward.  Well, gosh, I really enjoyed our conversation today. I think your study really reminds us how powerful genetic information is in terms of improving outcomes. And, you know, hopefully this will lead some individuals to perhaps test more broadly in appropriate settings. So, thank you so much, Matteo, for joining us today with your fantastic insights on the ASCO Daily News Podcast. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a real pleasure. Dr. Monty Pal: And thanks to our listeners too. You'll find a link to Dr. Lambertini's study in the transcript of this episode. Finally, 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 a ton. 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. Matteo Lambertini @matteolambe   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. 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. Matteo Lambertini: Consulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seagen, Menarini, Nordic Pharma Speakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, Libbs, Daiichi Sankyo, Gilead Sciences, AstraZeneca, Menarini, AstraZeneca, Menarini Research Funding (Inst.): Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Daiichi Sankyo Europe GmbH, Roche

In this JCO Article Insights episode, Dr. Ece Cal interviews Dr. Martin Wermke, author of the JCO article, "Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas." TRANSCRIPT The disclosures for guests on this podcast can be found in the transcript. Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO editorial fellow, and today I am joined by Dr. Martin Wermke, Professor for Experimental Cancer Therapy at Dresden University of Technology, to discuss the manuscript “Phase 1 Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-like T-Cell Engager Obrixtamig in Patients with DLL3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas.” Obrixtamig is a bispecific T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells. This manuscript presents the phase 1A dose escalation results of Obrixtamig in patients with DLL3+ small cell lung cancer and neuroendocrine carcinomas. In this study, 168 patients were treated with Obrixtamig across four different dosing regimens. 49% of the patients had small cell lung cancer, 42% had extrapulmonary neuroendocrine carcinoma, and 8% had large cell neuroendocrine carcinoma of the lung. Patients received a median of two prior lines of therapy. 33% of the patients had brain metastases at baseline. Of note, this trial did not mandate baseline brain imaging. Maximum tolerated dose was not reached. 88% of the patients experienced a treatment-related adverse event, however, only 3.6% of the patients had to discontinue treatment due to treatment-related AEs, and dose reduction due to treatment-related AEs was documented in 2.4% of the patient population. Similar to the other DLL3-targeted bi-therapies, the most common adverse events included CRS in 57%, dysgeusia in 23%, and pyrexia in 21% of the patients. CRS events were mostly mild. They occurred more frequently in the first two to three doses. 9% of the patients experienced ICANS, of which 3% were graded as Grade 3 or higher. And let's review the efficacy results. Responses were only seen in patients who received 90 microgram per kg or more once weekly or once every three weeks dosing. The objective response rate in patients who received an effective dose was 28%. If we review by tumor type, 21% of the small cell lung cancer patients, 27% of the extrapulmonary neuroendocrine carcinoma patients, and 70% of the large cell neuroendocrine carcinoma patients had objective response. Median duration of response was 8.5 months, though this data is immature due to short follow-up. Dr. Wermke, DLL3-targeted bispecific T-cell engagers are reshaping the treatment landscape of small cell lung cancer. This trial investigates Obrixtamig in other high-grade neuroendocrine tumors as well. Can you put this trial into context for us and explain why it may represent an important step forward? Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to discuss our data today. I think the data with Obrixtamig in small cell lung cancer are largely similar to what has been observed with other bispecific T-cell engagers such as tarlatamab with respect to the response rate and duration. It has, however, been to be mentioned that BI 1438001 had a bit more liberal inclusion criteria than other trials around. You already mentioned the fact that we allowed the inclusion of patients without mandatory brain imaging, which led to some patients having their brain mets been diagnosed during the treatment with obrixtamig and then adding to the progressive disease patients. That is something which was not the case with the tarlatamab trials where you really had to have a brain imaging before, and in the Phase 1 trial you were even required to treat the brain mets before you included the patient. So it is a bit different, more poorest patient population. I think the trial adds on existing data by being the first trial to also include non-SCLC neuroendocrine carcinoma of other origin, for example from the gastrointestinal tract, and also by including large cell neuroendocrine carcinoma of the lung, which is a really hard to treat pulmonary neoplasm which currently lacks any standardized treatment. So that is really a step forward which we will build on in the future. Dr. Ece Cali: And one thing I would note in this trial, only patients with tumor expressing DLL3 were enrolled. Can you tell us a little bit more about this target, DLL3 in the context of neuroendocrine tumors, and does DLL3 expression predict clinical outcomes after treatment with DLL3 BiTEs, or do we actually need other predictive biomarkers for these novel agents? Dr. Martin Wermke: Yeah, thank you. That's a pretty interesting question. First of all, DLL3 is an atypical notch ligand, which is expressed by the majority of neuroendocrine carcinomas, virtually absent on healthy adult tissues. Therefore, turning it really into a bona fide target for T-cell engaging therapies, pretty low risk for on-target off-tumor side effects. We found that in all the patients we screened, we had an expression rate of about 94% in small cell lung cancer, 80% of large cell neuroendocrine carcinoma of the lung were positive, and also about 80% of the extrapulmonary neuroendocrine carcinoma. So it's really a high prevalence. So the fact that we only included DLL3+ tumors still means we included most of the patients that presented with these diseases. I think at the moment there are no data suggesting a clear-cut association between DLL3 expression levels and outcome on DLL3 CD3 T-cell engagers. There's also not a lot published. If you want to find this out for tarlatamab, you have to look into their patent to really see the data, but it's not clear-cut and I'm sure we need other markers to complement that. And I think what probably plays a major role is intrinsic T-cell fitness. So the question how really diseased your T-cells are, how old you are, because age also correlates with the fitness of the immune system, and other patient characteristics such as tumor burden, we've seen all across the board that the higher the tumor burden, the lower the rate of prolonged response is in such trials. And I also think we need to focus on other components of the tumor microenvironment. So see how high the T-cell infiltration with obrixtamig is and how abundant suppressive elements like regulatory T-cells or myeloid-derived suppressive cells are. That is work which is currently being done. Data are emerging, but I don't think that at the moment we have any clear biomarker helping us to select who should not receive DLL3 T-cell engagers. Dr. Ece Cali: Those are great points and there is a lot we need to learn about how to use these novel agents in the future. I'd like to highlight the results in large cell neuroendocrine carcinoma of the lung. The response rate in this group was remarkably high at 70%. Though we should note the small sample size of only 14 patients in this trial. After first line chemoimmunotherapy, current approved options for this population have very modest clinical activity. Given these trial results, how do you envision the field moving forward for patients with large cell neuroendocrine carcinoma? Dr. Martin Wermke: Yeah, I think LCNEC is really an area which urgently needs further improvement of therapeutic standards. At the moment, as I said, there is no real standard. We are usually extrapolating from results we have in small cell lung cancer or non-small cell lung cancer, but I don't think we have too many prospective trials really informing this. Of course, 14 patients is a small sample size, but I think it's still fair to say that we can claim that DLL3 T-cell engagers are not doing worse in LCNEC than they do in SCLC. And that's why I think we really need to move forward clinical trials that are specifically targeting this population. Although I fear a bit that, given the rareness of this disease and the aggressiveness of its phenotype, that this is probably not the main focus of the pharmaceutical industry. So I think it's up to us academic investigators to really come up with investigator-initiated trials trying to fill the knowledge gaps we have here. Dr. Ece Cali: And one more thing that I want to talk about is the accessibility for these drugs. These novel agents are showing real promise in improving outcomes for patients with high-grade neuroendocrine tumors, an area where progress has been limited until very recently. However, as DLL3 BiTEs become more widely used, issues of logistics and access come into sharper focus. With unique toxicities and the specialized monitoring, their use is restricted to certain centers. Looking ahead, what kinds of strategies could help mitigate some of these adverse events or make these treatments more broadly available? Dr. Martin Wermke: Yeah, I think if you look at countries like the United States where tarlatamab has already been approved, we can see how the management strategies are evolving. I've heard about a colleague equipping their patients with thermometers and a pill of Dexamethasone, alongside with a temperature control protocol and clearly instructing them, "If you measure a temperature above a certain level then start taking the Dexamethasone and come back to our office and we're going to take care of you." I think that's one way to move forward. I think we are lucky in a way that CRS usually manifests within the first 24 hours. This was the same in our study, like in the tarlatamab studies. So we really know when the time of trouble is for our patients. And in this time, I think we need to instruct the patients to stay close to the hospital. I don't think we need to hospitalize all of them, but we probably need them to stay in a nearby hotel to be able to reach the emergency room if needed in a short period of time. And I think we can also learn in this strategy how to manage bispecific antibodies from the experience our colleagues in hematology had because they have been using bispecific T-cell engagers for quite some years right now and they developed strategies and networks that were able to successfully treat these patients also on an outpatient basis. And I think that is clearly an experience we need to follow, acknowledging that we are talking about diseases which are much more frequent than the standard hematology indications. Dr. Ece Cali: Thank you so much, Dr. Wermke, for this informative discussion and for sharing your perspective on this evolving field. Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to talk about data. It was really great being able to share that, and I really think that we are just at the beginning of a new exciting area for the treatment of neuroendocrine carcinomas, and I think much improvement is yet to come for our patients. Dr. Ece Cali: Yes, that's really exciting. And thank you everyone for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit 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 this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Martin Wermke's Disclosures Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer,  BMS GmbH & Co. KG, Regeneron, MJH/PER, Takeda Consulting or Advisory Role: Bristol-Myers Squib, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics, AstraZeneca, Tacalyx, Regeneron, Daiichi Sankyo Europe GmbH, Zymeworks, PharmaMar, Iovance Biotherapeutics, T-Knife, Genentech Research Funding: Roche Patents, Royalties, Other Intellectual Property Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, AstraZeneca,  Amgen,  GEMoaB, Sanofi/Aventis, immatics,  Merck Serono, Janssen Oncology, Iovance Biotherapeutics, Daiichi Sankyo Europe GmbH"

Interviewees: Kirsten Brown, PhD Assistant Professor of Health Professions Education at the Uniformed Services University of the Health Sciences; as a short disclaimer, Kirsten's views do not represent the official policy or position of her employer.  Dionna Bidny, MD, MMUS  a first-year resident in Physical Medicine and Rehabilitation at the University of Pittsburgh Medical Center, currently completing her Transitional Year; and Abby Konoposky, PhD Senior Director of Medical Education Research in the Department of Psychiatry at Northwell Health. Interviewer:  Lisa Meeks, PhD, MA, Guest Editor, Academic Medicine Supplement on Disability Inclusion in UME. Description: This episode of Stories Behind the Science brings you an intimate conversation with Dr. Kirsten Brown (Uniformed Services University of the Health Sciences), Dr. Dionna Bidny (University of Pittsburgh Medical Center), and Dr. Abby Konopasky (Northwell Health), co-authors of Disability in Undergraduate Medical Education in the United States: A Scoping Review, part of the Academic Medicine supplement on Disability Inclusion in Undergraduate Medical Education. Drawing from over 80 publications, their study traces how disability in medical education has too often been framed through deficit and legal models, while leaving intersectionality and the voices of disabled learners largely absent. Together, we explore why this framing matters, what the literature reveals about gaps and progress, and how a critical perspective can re-shape the field. Our guests share the personal and professional motivations behind this ambitious review, the surprises and challenges they encountered, and their hopes for how this work can serve as both roadmap and catalyst. Whether you are a researcher, faculty member, disability resource professional, or student, this episode offers insights into the state of the field and inspiration for charting new directions. Resources and links to the open-access article, Disability Resource Hub, and related tools are in the show notes. Transcript: https://docs.google.com/document/d/1iUYE0Q-2TA1flXiMU6rum1S3dO-obE5DoA9J0mFmHlE/edit?usp=sharing Bios:   Kirsten Brown, PhD Dr. Kirsten Brown's research examines the intersection of disability, power, and social systems. Her work has appeared in the Journal of College Student Development, the Journal of Diversity in Higher Education, and Journal of Higher Education. She co-authored the book Disability in Higher Education: A Social Justice Approach. Dr. Brown prepared this chapter during non-work hours as an independent scholar and this publication did not receive funding from the federal government. The views expressed are solely those of the author and do not represent the official policy or position of the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, the Department of Defense, or the U.S. Government.  Abigail Konopasky, PhD Abigail Konopasky holds doctorates in educational psychology from George Mason University and in linguistics from Princeton University. She is currently an Associate Professor and Director of Medical Education Research and Scholarship in the Psychiatry Department at Northwell Health. She conducts critical qualitative and mixed methods research in health professions education, with a focus on equity, Black feminism, and critical disability studies using functional linguistic and narrative methods and theories of agency. She serves on the editorial boards of Teaching and Learning in Medicine, Perspectives on Medical Education, and Advances in Health Sciences Education. Dionna Bidny, MD, MMus  Dionna is a first year resident at the University of Pittsburgh Medical Center in Physical Medicine and Rehabilitation (currently  in her  Transitional Year). She has a BS in biomedical engineering and an  MMus in Musicology; she incorporated her interest in accessibility in arts, sports, and healthcare spaces through research during both degrees. In medical school, she continued to study and lecture in the space of disability  justice and its intersections with art, identity,  and healthcare experience, all  while navigating  chronic illness and pursuit of her own  accommodation and access needs. In residency, she aims to continue her work in accessibility within arts and sports through community engagement and engineering innovation. Key Words:   Disability in medical education Undergraduate medical education (UME) Disability inclusion Scoping review Academic Medicine supplement Deficit model vs. asset model Legal framing of disability Intersectionality in medicine Disabled learners' voices Critical perspectives in medical education Equity in medical training Accommodations in medical education Disability justice Ableism in medicine Representation in health professions Research roadmap Diversity and inclusion in medicine Disability studies in medical education Inclusive curriculum Systemic barriers in medical education Resources:  Article from Today's Talk Maggio, Lauren A. PhD; Brown, Kirsten R. PhD; Costello, Joseph A. MSIS; Konopasky, Aaron PhD, JD; Bidny, Dionna MD, MMus; Konopasky, Abigail PhD. Disability in Undergraduate Medical Education in the United States: A Scoping Review. Academic Medicine 100(10S):p S64-S73, October 2025. | DOI: 10.1097/ACM.0000000000006154 https://journals.lww.com/academicmedicine/fulltext/2025/10001/disability_in_undergraduate_medical_education_in.5.aspx   The Docs With Disabilities Podcast https://www.docswithdisabilities.org/docswithpodcast

Ben and Nate tackle another common misconception: "I have accommodations, so I should finish the section." They remind listeners to slow down if their accuracy is low, no matter how much time they have.Read more on our website. Email daily@lsatdemon.com with questions or comments. Watch this episode on YouTube!

Welcome to episode 108. If you've ever felt like the 9–5 world just isn't for you, you're not alone. This episode shines a light on why traditional jobs can feel overwhelming for those who are neurodivergent - think unclear expectations, social pressures, and sensory overload - and the opportunities that present themselves in self-employment. Starting your own business can bring freedom, fulfilment and confidence to be authentically you. Listen in for practical tips on avoiding burnout, outsourcing, and finding the confidence to build a work environment  in which you can thrive. Let's dive in! ·       Redefining the “rules” of work – Being your own boss and the freedom to design a work environment that supports your individual needs. ·       Finding your people - Why connecting with supportive communities builds understanding, encouragement, and a sense of belonging that traditional workplaces often lack. ·       Still an employee? There's good news - you don't need a formal diagnosis to ask for adjustments in the workplace.    This episode is sponsored by Georgia Cambridge, Pet Loss Counsellor Connect with Georgia here on Facebook.   SPECIAL LISTENER OFFER! Until 31st October 2025 join the Happier Life Hub for just £1. Easy to cancel after the first month, or £20pm thereafter if you'd like to continue. Get the offer HERE. Click here for all the details on the Happier Life Hub. If this podcast episode resonated with you and you'd like to support me to make more podcast content, please buy me a coffee here - https://ko-fi.com/happierlifecoach - your support is hugely appreciated. You can also connect with me over on Instagram @happierlifecoach  Remember to hit subscribe or follow to be alerted when new episodes go live!   Season 5 of this podcast is sponsored by Stephanie Ward of The Spicy Brain Collective. We thank Stephanie hugely for her ongoing support. https://www.thespicybraincollective.com https://www.instagram.com/thespicybraincollective https://www.linkedin.com/in/stephanie-ward-sbc

Host: Kate Brownfield, Certified Whole Person & ADHD Parent Coach Guest: Aimee Kaufman, author of No One Else I'd Rather Be: Loving a Daughter with ADHD for Who She Is Episode Overview In this profoundly moving conversation, Kate sits down with author and parent Aimee Kaufman to talk about her memoir and the 10-year journey to her daughter's ADHD diagnosis. Aimee shares the hard moments, misunderstandings, criticism, school challenges, and the hope that carried her family forward: unconditional love, advocacy, and support that matched her daughter's needs over time. If you're a parent who feels overwhelmed, second-guessed, or unsure how to keep leading with love during tough seasons, Aimee's story will encourage and steady you. What We Talk About (Highlights) A long road to clarity: Why it took 10 years to get an ADHD diagnosis—and what finally helped. When behavior says “I can't,” not “I won't”: How Aimee learned to interpret her daughter's words and actions. Unconditional love in the messy middle: Loving firmly and fully when emotions run high. School Support That Actually Helps: 504 Accommodations, When They're Ignored, and How to Advocate. Medication as one tool (not the only one): The trial-and-error reality and finding the right fit over time. Siblings & family dynamics: Moving from rivalry and rupture to healing and closeness. Parent grounding: How Aimee stayed steady—community, practical support, and protecting her own well-being. A hopeful ending: From crisis to connection—college, career, marriage, and a growing family. Resources & Links Aimee Kaufman's Book: No One Else I'd Rather Be: Loving a Daughter with ADHD for Who She Is — https://www.simonandschuster.com/books/No-One-Else-Id-Rather-Be/Aimee-Kaufman/9781647428280 About Your Host, Kate I'm Kate Brownfield, Certified Whole Person & ADHD Parent Coach, author of How We Roll: A Parent's Journey Raising a Child with ADHD, and host of The ADHD Kids Can Thrive Podcast. It's honestly my pleasure to help you understand ADHD more deeply—because every child with ADHD is unique, and so are their strengths and struggles.

Dr. Monty Pal and Dr. Mina Sedrak discuss the science behind cancer treatment-induced accelerated aging and the development of drug therapies and technologies aimed at helping older patients and cancer survivors. TRANSCRIPT Transcript: Cancer and Aging: Researching the Path to Longer, More Vibrant Lives Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Monty Pal. I am a medical oncologist and professor and vice chair of medical oncology here at the City of Hope Comprehensive Cancer Center. I am also host of this podcast. Today, we are going to be talking to somebody that I consider to be my little brother, if you will, in oncology, Mina Sedrak. Mina is an expert in the area of cancer and aging, which really includes the development of drug therapies and technologies that help enable older adults and survivors to live longer, healthier, and more vibrant lives. I am really excited to chat with him. He is an expert not just in cancer and aging but also breast cancer. He was my former colleague here at City of Hope before he moved over to the UCLA Jonsson Comprehensive Cancer Center, where he is an associate professor and director there of the Cancer and Aging Program. Dr. Sedrak's research involves mechanisms behind cancer treatment-induced accelerated aging and really aims to take this science into more of a therapeutic direction, which I am super, super excited about.  Mina, thanks so much for joining us today, and just FYI for our listeners, we have all of our disclosures in the transcript of this episode. Dr. Mina Sedrak: Thank you, Monty. Thank you, Dr. Pal, for having me. I am really excited to be here. Dr. Monty Pal: I feel like we have to go on a first-name basis here with how well we know each other. So Mina, you and I together have witnessed this evolution in cancer and aging. I mean, both of us worked together here with just a legendary figure in the field of geriatric oncology, I will call it, Dr. Arti Hurria, mentor to me, mentor to you, mentor to so many. Can you give us a sense of where cancer and aging has gone since the time that you and I started here together at City of Hope? Dr. Mina Sedrak: Dr. Hurria and her collaborators, Dr. [Willliam] Dale and Dr. [Supriya] Mohile, they were like huge pioneers in the field. They were one of the very first people to highlight the importance of looking at older adults beyond just their chronological age and their comorbidities and moving us beyond just seeing patients and making decisions using what we call the eyeball test. "Oh, this person looks fit or not fit, frail or robust," to really using objective measures to assess our patient's health status and incorporate that assessment into our evaluation of the treatment, prognostication, and discussions with our patients throughout the cancer continuum. And so that is what geriatric oncology has and continues to be, and it is a huge, important part. And their work has laid the foundation to show that when we look at our patients beyond just their chronological age and we look at their functional age, and we do these objective assessments, we can gain much more deeper information to tailor the treatment for our patient that is sitting in front of us, rather than do a prescriptive treatment or over- or undertreatment in that population. So that is sort of where the field is growing, and a lot of the work now is, how do we implement that? How do we put that into clinical practice? Dr. Monty Pal: Well, let me kind of spearhead that discussion, right? I have these moments when I go to the ASCO Annual Meeting – I remember this happened to me a while ago when Dr. Jennifer Temel presented that terrific work around early palliative care interventions, right? Or it even happened to me this year, right, when Dr. Christopher Booth presented the CHALLENGE trial around exercise and colon cancer. You know, these amazing, I am going to say simple, they are not simple, but they are simple interventions relative to, you know, some of the complex drugs and mechanisms that we are using nowadays that really help outcomes for our cancer patients. The big question becomes, how do you implement, right? But my understanding is that there are easy ways for us to take tools in cancer and aging and sort of plug them into our daily practice. Am I right about that? Dr. Mina Sedrak: Yes, and that is something that they are – the Cancer and Aging Research Group, which was founded by Dr. Hurria and now is co-led by Dr. Dale, Dr. Mohile, and Dr. [Heidi] Klepin, they have been incredible at really trying to develop practical tools, like the Practical Geriatric Assessment, which is now endorsed by the ASCO and other NCCN guidelines. And so, there are tools that are becoming more and more practical to help incorporate that into clinic.  Now, what might be practical in a resource-intensive setting may not be practical in some of the limited resources, whether it is rural and/or other countries where the resources may be more limited. So that is why Cristiane Bergerot, Enrique Soto, and others have been really working hard. There was actually a really beautiful paper that was just published in the Journal of Global Oncology, where they have shown that there are guidelines [ASCO Geriatric Assessment Global Guideline] about how to implement these tests, these tools, these assessments in clinical practice, even in different resource settings. So I think we are going to get to the future where this is much more – it is definitely important, but it is much more easily ‘incorporatable' into our practice. Dr. Monty Pal: Yeah, you know how close I am to Cris, and I was so proud when I saw that paper come out. That was really exciting. You know, I skimmed it. I have to tell you, I did not get into the weeds, but it was apparent to me that, you know, some of these geriatric oncology tools are things that, you know, I could probably plug and play into my practice where I am double- and triple-booked over, you know, most slots, right? I mean, I could still probably afford a little bit of time or maybe have, like, a nurse or an extender kind of help participate in the evaluation process. I thought that was, yeah, really, really interesting. Dr. Mina Sedrak: I will just say that at UCLA, we are working with Dr. Arash Naeim, who is a geriatric oncologist, and he has developed an AI platform where the assessments can be done by an AI computer. So it is like talking to your ChatGPT. They can talk to you, and for a few minutes, they will ask you the questions. So you do not even have to fill it out on a piece of paper. You could give the patient a little iPad, put them in a private room while they are waiting for their doctor, and get the results, and it is right there for you. And so, we have been trying to think about how can technology help with the completion of the assessment, at least doing that? And I think it is actually, it has been very cool. We did a pilot study. He is writing that up, and we are going to continue to do some of this exciting work. How do we think about AI in the context of this? And, you know, older adults, they are not like what they used to be. A lot of older adults are very familiar with and comfortable with phones and computers and iPads, much more so today than they were even at the time when Dr. Hurria was alive. Dr. Monty Pal: That is so interesting. You mentioned this, the AI approach is something I have been thinking about in this context because what if, for instance, you know, we have got video monitors all over our hospital, right? What if you are actually just taking a look at that patient as they make their way towards your clinic? Capture that video, use an AI algorithm to say, "Hey, you know, the timed get-up-and-go test in this patient is not particularly good based on what I am seeing here," right? There are so many ways that you could, you know, stir the pot and come up with creative ways to get these tests done. Dr. Mina Sedrak: That's right. And Arash is looking at also sensors. So he has some studies where he is putting sensors inside people's homes, where they would put them, like, on top of an Alexa app or the equivalent. A lot of people have these apps, and basically, they can sense how you are moving around and what you are doing, just movement-wise. And then they can collect that information to gain information about your life beyond just what we are seeing in the 20-minute visit in the clinic. Even when I do a walk test where I get gait speed or physical performance, short physical performance battery, the chair sit-up, those are oftentimes a single, cross-sectional, static measure. But what about the dynamic ability of capturing what has been happening for the last 7 days? What has been happening for the last 25 days between the visits, between the cycles of chemotherapy? And could that inform how I make decisions when I see patients and who do I need to target and identify? And so, we are very excited because really at UCLA, Arash is leading the technology efforts and thinking about implementation of these important measures and these important tools but leveraging new technology. And we do not want to be behind; we want to be ahead of the game. Dr. Monty Pal: I love that idea because there is a Hawthorne effect, isn't there, where you observe a process, and it naturally gets better. I mean, when you ask that patient to get up in the clinic and move, they are probably functioning to the best of their abilities, but we could probably learn a lot from just watching how fast that patient picks up a remote control at home. Some simple movement like that that is volitional would probably help out a ton. And I got to tell you, it is so funny when you mention Arash Naeim's name. I distinctly remember him serving as an attending on the wards when he was brand new at UCLA on faculty when I was a resident there. And his dad is a legendary hematopathologist, right? Dr. Mina Sedrak: I did not know that. Dr. Monty Pal: Yeah, yeah. Faramarz Naeim wrote the book on a lot of heme-path malignancies. Incredible guy. Very, very storied hematopathologist at UCLA.  I could probably go on this topic forever, but in the interest of time, I am going to shift to something that again, I could probably talk about forever, which is this area of senescence that you are involved in. You know, you had mentioned this to me, I am going to say during your outro from City of Hope and towards your transition to UCLA, it is such an exciting area. I mean, understanding the actual biologic process of aging and using those underpinnings to really sort of tailor therapy. So tell us where the state of the science is there with this body of work that you are doing. Dr. Mina Sedrak: As I said before, we have tools now to assess patients and to then do something about the deficits. So if a patient is falling, what we do is we refer them to physical therapy where they can do fall precautions and strength training to give them the information. But all of these supportive care interventions are very important. They are great. But they oftentimes are not targeting the root cause of why they are happening. And so that is really where I have been very interested in, how can we understand why is it that something like chemotherapy or immunotherapy is causing a decline in cognitive function or a decline in physical function? And so that has really led us to think about geriatric oncology rather than a discipline of older adults, but to think about aging as a physiologic process. We are all aging. As every day goes by, we are aging. And what that means is that our bodies are accumulating damage, the cells are being exposed to various stressors, and the repair mechanisms are declining. And as we get older, it is really more damage and less repair mechanism at the cellular molecular level. And it turns out that these processes of how our cells repair and respond to damage are fundamental processes of biological aging. And there has been a large amount of preclinical and now really exciting clinical work to show that there are hallmarks that could be used to assess the rate of which we age by looking at these processes. And that includes things like epigenetics, telomeres, inflammation, and something called ‘cellular senescence.' And we have been interested in my lab in senescence because it is a unique process that has an important role in aging, but it also has a really important role in cancer. Senescence is a cell state. Cells, when they are stressed, they respond to entering this state of senescence. The stress could come from anything. It could come from an oncogene activation. It could come from a reactive oxygen species. It could come from a direct damage to the cell. But it is a cell state, just like apoptosis, necrosis. Senescence is a state in which the cell, in response to that stressor, undergoes an arrest from the G to the S phase. And that arrest is oftentimes associated with a resistance to apoptosis. So then the cell does not die, but it is alive, and it remains metabolically active. And in fact, downstream pathways of these cell cycle inhibition of this G-to-S phase lead to the increase of these transcription factors in the chromatin and lead to the development of these pro-inflammatory factors. So these cells, which can occur in various tissues in the body, can continue to live despite having developed these changes, and then they secrete these proinflammatory molecules like cytokines, chemokines, metalloproteinases, all of these, which are called the senescence-associated secretory phenotype, or SASP. And as we age, we accumulate more and more of these cells, and our bodies are no longer able – our immune system, like macrophages and T cells – are no longer able to remove them effectively. And as we accumulate them in various organs, these organs release a lot of inflammatory cytokines, and the chronic inflammation in that tissue leads to the tissue being damaged, and it does not work as well, and then it starts to decline in function. And that is believed to be how senescence plays a role in aging. It is the accumulation of senescent cells that occurs with increased damage and then the repair mechanism of clearing these cells effectively, which then leads to build up of inflammation and chronic inflammation leads up to damage in multiple tissues. Dr. Monty Pal: This concept to me is fascinating. And I guess the big question is – senescence is bad, right – is it not reasonable to think that this body of research, I mean, if you are able to sort of have a meaningful impact on senescence, it could have implications well beyond oncology. Is that fair? You really could extend lifespan all around. Is that reasonable to think, all-cause mortality? Dr. Mina Sedrak: One hundred percent. And that is what they have been shown in animal models. And the reason senescence is exciting is because it turns out that you can target these cells and you can induce apoptosis of these cells, but it requires active targeting of various pathways, but it can occur. And when it does, and it is done either genetically or pharmacologically in mice, we see that the mice can reverse damage. So if you take an old mouse and you genetically engineer it to remove senescent cells, that mouse will go from being frail to fit. And if you take a young mouse and you induce senescent cells at a high rate and you accumulate them in that mouse, that mouse, even though it is young, will become frail.  So that has really led to this exciting opportunity of, can we translate this finding that we are seeing in animals and in in vivo cells, cell cultures, into humans? And could that have a benefit beyond just one disease? Could it have a benefit in multiple diseases? And not just really longevity, which I think it would be great, but what people are really looking for is, how do we live healthy as we get older? How do we move the curve so that people are not developing chronic diseases in their 60s, but they are developing them in their 80s towards shortening the period of their life with disability rather than what we have currently, which is people are living to 70s, the average life expectancy is in the mid-70s, but they are spending 10 or 11 years in disability of that life. And so, how could we reduce that time frame? Dr. Monty Pal: This is brilliant, Mina. And for our audience, this compelling dialogue that we have had here thankfully is translating to funding for Mina's work. He just scored in the second percentile for his NIH R01 based on this topic. We are so, so proud of you. I mean, it is just remarkable work. It is not easy in the current climate to get funding, and a second percentile score is just absolutely wonderful. You know, Mina, I could probably go on with you for a couple more hours here talking about your work in cancer and aging. I think I am going to have to have you back on the podcast here. But a million thanks for sharing your thoughts here today on the ASCO Daily News Podcast.  And thanks to our listeners too. If you value the insights that you heard today on the ASCO Daily News Podcast, please do not forget to rate, review, and subscribe wherever you get your podcasts. Thanks, Mina. Dr. Mina Sedrak: Thank you so much. 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. Mina Sedrak @minasedrakmd   Follow ASCO on social media:      @ASCO on Twitter     ASCO on Bluesky    ASCO on Facebook      ASCO on LinkedIn      Disclosures:     Dr. 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. Mina Sedrak: Patents, Royalties, Other Intellectual Property: Up-to-Date

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

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 

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.

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/

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!

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