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:
You can find us on X:Gut Onc Lab (@TheGutOncLab) / X
Contributors:
Dr. Nicholas Hornstein, MD, PhD, is a gastrointestinal medical oncologist and Assistant Professor Northwell Health.
Dr. Timothy Brown, MD, MSCE, is a gastrointestinal medical oncologist and Assistant Professor at UT Southwestern.
Dr. Udhayvir Grewal, MD, MBBS, is a gastrointestinal medical oncologist and Assistant Professor at Emory University School of Medicine.
