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