The Gut-Onc Collab: Universal Testing Laws, BRCA1 Discordance, and the RAS Wave with Dr. Kim Reiss

The Gut-Onc Collab: Universal Testing Laws, BRCA1 Discordance, and the RAS Wave with Dr. Kim Reiss

On this in-person episode of The Gut Onc Lab podcast, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal welcome world-renowned BRCA specialist Dr. Kim Reiss to dismantle the historic view of pancreatic cancer as a monolithic, chemo-only disease. The group dives deep into the 5% to 9% of pancreatic ductal adenocarcinoma (PDAC) patients harboring germline or somatic homologous recombination repair (HRR) defects and how to maximize their survival. Key discussion points include: * First-Line Crosscurrents: Why the team remains FOLFIRINOX traditionalists over the newly approved NAPOLI-3 Nalirifox regimen, and the operational reality that universal testing must start at day zero. * The APOLLO Trial Blueprint: Dr. Reiss details the international Phase III ECOG-ACRIN EA2192 trial—mirroring breast cancer's landmark Olympia study—bringing a year of adjuvant olaparib maintenance into the curative-intent space. * Brainwashing Fellows & Hunting Rare Variants: Raw advice for junior investigators on leveraging advocacy groups, social media, and temporal NGS tracking to keep specialized clinical trials accruing. * The BRCA1 vs. BRCA2 Paradox: Dissecting Dr. Talia Golan’s Cancer Discovery data revealing why 50% of BRCA1 pancreatic tumors are actually sporadic bystander events, compared to the 90% true biallelic loss seen in BRCA2. * Dismantling Negative Data: A critical look at SWOG 2001 and the European durvalumab/olaparib updates, explaining why adding immunotherapy to PARP inhibitors failed broadly across all-comers unless a specific T-cell inflamed microenvironment is isolated. * The Golden Era of Targeted PDAC: Looking past the immediate RESOLUTE-302 pan-RAS plenary drop to the fast-approaching pipelines of Claudin 18.2 combinations and MTAP-deletion / PRMT5 inhibitors. From the immediate necessity of split-dose Cis-Gem pivots to a world where targeted pills dominate frontline care, this conversation frames the exact moment pancreatic oncology permanently moved into the precision era.   Chapters (00:00) Why Pancreatic Cancer Needs Better Options (01:29) First Line Chemo Choices Today (02:33) Testing and When to Pivot (04:19) Subtype Assays and Practical Limits (05:59) POLO and PARP Maintenance Lessons (07:49) APOLLO Trial Design and Progress (09:28) Recruiting Rare Variant Patients (11:34) Standard Care for BRCA PALB2 (12:13) BRCA1 vs BRCA2 Biology and HRD (13:48) ASCO Outlook and KRAS Era (15:54) PARP Plus Immunotherapy Biomarkers (19:12) Closing Thoughts and RAS Revolution You can find us on X: Gut Onc Lab (@TheGutOncLab) / X [https://x.com/TheGutOncLab]

The Precision Shift: Re-Writing the Colorectal Cancer Roadmap with Dr. Arvind Dasari

In this special in-person episode filmed straight from the floor at ASCO 2026, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal welcome guest Dr. Arvind Dasari (MD Anderson) to discuss why colorectal cancer is officially having its precision medicine moment. From the epidemic of young-onset disease to the frontline tracking of ultra-specific biomarkers, the panel discusses why molecular profiling is now just as critical as a histological diagnosis.    Key discussion points include: * Universal Testing & The ALASCCA Data: Why every patient—localized or metastatic—requires immediate biomarker staging, including a look at using adjuvant aspirin to target PI3K/PTEN/PIK3CA pathway alterations.  * The CIRCULATE-North America Blueprint: Dr. Dasari shares the technical and regulatory hurdles of designing a major serial ctDNA trial, the removal of the Phase II/III FDA hold, and how the study is dynamically expanding eligibility rules for stage III de-escalation.  * The Turnaround Revolution: A practical look at clinic operations in 2026—how combining liquid biopsy with fast-tracked DPYD and UGT1A1 panels delivers actionable genomic results in under seven days.  * Targeting the Known Frontiers: Breaking down the current state of Breakwater (BRAF V600E), CheckMate 8HW (Nivo/Ipi doublets in dMMR), and the downstream nuances of RAS co-occurrence in HER2-targeted therapies vs. ADCs.  * Post-Conference Takeaways: The panel's real-time analysis of the major ASCO abstracts, including the Dutch PUMP trial (adjuvant hepatic artery infusion pumps for liver metastases) and the data validating the cessation of immunotherapy for complete responders.    From institutional operator expertise in HAI pumps to the future of "unknown target" molecular glues, this session bridges the gap between massive data drops and Monday morning clinic realities.    Chapters: (00:00) Welcome and Introductions (00:54) Meet Dr Dasari (04:15) Who Gets Molecular Testing (07:41) CIRCULATE Trial Explained (09:00) Trial Design Challenges (14:11) Whats Next in CRC Therapy (16:16) HER2 Positive Approach (17:02) ASCO Highlights and Practice Changers (18:43) Nonoperative and Supportive Care (20:25) HAI Pump PUMP Study (21:45) Closing Thoughts and Sign Off   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X [https://x.com/TheGutOncLab]

ASCO 2026: GI Oncology Abstracts to Look Forward To.

With the 2026 ASCO Annual Meeting just days away, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal sit down for a rapid-fire, "mouth-to-butt" preview of the most practice-altering abstracts hitting the floor in Chicago. Armed with top-line press releases and early data, the team highlights their top three high-stakes selections across the entire GI tract. Key previews include: * The Upper GI Blockbusters (Tim’s Picks): Updated HORIZON-GEA data showing why HER2/PD-1 bispecific synergy doesn't care about baseline PD-L1 expression; a compliance deep-dive from the Matterhorn trial; and the arrival of IsaBrin (an EGFR/HER3 bispecific ADC) moving the needle in second-line squamous cell esophageal cancer. * The Midgut & Plenary Hype (Udhayvir’s Picks): Front-row seats for RESOLUTE-302, the monumental plenary session showcasing deruxantrib doubling overall survival (13 months vs. 6.7 months) in second-line RAS-mutant pancreatic cancer. Plus, the PHITE-302 trial proving frontline pemigatinib works for FGFR2-rearranged cholangiocarcinoma despite notorious accrual challenges. * Below-the-Belt Tech & Wild West De-escalation (Nick’s Picks): The highly anticipated late-breaking PUMP trial testing adjuvant hepatic artery infusion (HAI) pumps for colorectal liver metastases. Then, a massive look at China's Abstract 3502, confirming that MSI-High colorectal patients who hit a Complete Clinical Response can safely stop maintenance immunotherapy and maintain a 100% 3-year overall survival rate. * The Sci-Fi Future: A look outside the box at the Archer trial in lung cancer—utilizing a prophylactic peptide vaccine to train the immune system to short-circuit targeted therapy resistance mutations before they occur. Chapters: (00:00) Welcome and ASCO Preview (00:46) Top Three Picks Setup (01:28) HORIZON GEA HER2 Triplet (03:55) Matterhorn DFLOT Completion (06:11) IsaBrin for ESCC Second Line (08:10) RESOLUTE-302 RAS Inhibitor (13:12) PHITE 302 Pemigatinib Frontline (20:10) PUMP Trial Hepatic Infusion (24:02) MSI-High CRC Stop PD-1 (29:15) Archer Vaccine vs Resistance (33:30) Closing Thoughts and Chicago   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X [https://x.com/TheGutOncLab]

Organ Preservation in Upper GI Cancers

In this landmark fifth episode of The Gut Onc Lab, Drs. Nicholas Hornstein and Timothy Brown welcome their first guest, radiation oncologist Dr. Nina Sanford, to discuss one of the most significant shifts in modern oncology: Organ Preservation. Historically, esophageal and gastric cancers have required highly morbid, "life-changing" surgeries. Today, the team explores how we can leverage advanced imaging, radiation, and immunotherapy to potentially spare the organ without sacrificing survival.   Key highlights include: * Defining Organ Preservation: Why avoiding esophagectomy or gastrectomy is the goal, provided we maintain oncologic outcomes. * The SANO Trial Deep Dive: A look at the Phase 3 data establishing "Watch and Wait" as a non-inferior strategy for complete responders, and the modeling studies that suggest where surgery might still pull ahead long-term. * The MSI-High Exception: How medical oncology is leading the way with chemo-free immunotherapy (PD-1 and CTLA-4 doublets) to achieve near-miraculous clinical complete responses in a subset of patients. * Radiation as a Biological Tool: Dr. Sanford explains why "one-size-fits-all" radiation is a thing of the past. * The Burden of Surveillance: A realistic look at "Time Toxicity"—the intensive endoscopy, PET, and CT schedules required to safely manage patients who forgo surgery. * Multidisciplinary Buy-In: Why organ preservation isn't just about biology; it’s about having a surgical team ready for "salvage" and a GI team dedicated to frequent monitoring. Whether you're curious about the biological "Magic Rays" of radiation or the latest "Infinity" and "NEONIKA" trial results, this episode defines the current frontier of upper GI sparing.   Chapters: (00:00) Why Organ Preservation Matters (03:48) Immunotherapy Enters the Chat (06:45) Key Evidence for Watch and Wait (09:45) Quality of Life and Long Term Tradeoffs (13:10) Radiation Dose and Adaptive Future (17:32) Cross vs FLOT and RT in Gastric (20:38) MSI High Chemo Free Pathway (26:48) Surveillance Protocols and Logistics (28:23) Ideal Candidates and Feasibility (31:43) Infrastructure for Community Practice (33:03) Final Takeaways and Wrap Up   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X [https://x.com/TheGutOncLab]

MSI-High in GI Oncology: When Biology Opens the Door

In this episode of The GutOnc Lab, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal break down MSI-High GI cancers. A cancer diagnosis is never good news—but this is a setting where tumor biology meaningfully changes what’s possible, with immunotherapy offering real potential for durable responses and even cure.    Key discussion points include: * MMR vs. MSI: A diagnostic primer on the difference between IHC (protein) and NGS/PCR (molecular), including how to handle the discordance. * The “Parachute” Data: Breaking down the practice-changing CheckMate 8HW results—and why a hazard ratio of 0.21 is hard to ignore. Nick walks through why nivo/ipi is increasingly his frontline default. * The COMMIT Curveball: Why the COMMIT trial data didn’t deliver—and what it may tell us about PD-L1 vs PD-1 strategies in colorectal cancer. * Pseudoprogression vs Hyperprogression: Tim shares practical, in-the-clinic ways to tell whether a scan is showing immune infiltration… or true disease acceleration. * ctDNA at 6 Weeks: How Nick uses early ctDNA dynamics as a real-time readout of response—especially when you’re pushing toward non-operative management. * When IO Fails: What next? From CTLA-4 “immune salvage” approaches to where targeted therapy (including BRAF-directed options) fits. Whether you’re screening for Lynch or choosing between single-agent PD-1 and dual checkpoint blockade, this episode covers how we’re actually managing dMMR/MSI-H disease right now.   Chapters: (00:00) MSI High Basics (02:31) MSI vs MMR Methods (05:12) Choosing Tests in Practice (09:59) TMB Pitfalls (12:14) Pivotal Immunotherapy Trials (15:13) CheckMate 8HW Results (21:03) Biomarkers for Ipi Nivo (25:47) PD1 vs PDL1 Debate (31:52) Using ctDNA in Practice (34:42) How Long to Treat   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X [https://x.com/TheGutOncLab]