Upper GI Treatment Algorithm (Esophageal, Gastric, GEJ) - Dr. Sam Klempner

Treatment algorithms for upper GI cancers, including esophageal, GE-junction, and gastric adenocarcinoma, have shifted toward intensive systemic therapy and biomarker-directed approaches. For resectable disease, the standard of care involves peri-operative durvalumab combined with FLOT chemotherapy, followed by surgery and continued durvalumab to improve event-free and overall survival. Metastatic management requires precise assessment of HER2, MSI, PD-L1, and Claudin 18.2 status to guide therapeutic selection. Zanidatamab now serves as a preferred option for HER2-positive cases, while Zolbetuximab targets Claudin 18.2, necessitating careful management of gastrointestinal toxicities. Dr. Sam Klempner, a GI medical oncologist at MGH, emphasizes that while second-line options like paclitaxel and ramucirumab remain standard for biomarker-negative disease, the field is rapidly evolving with the integration of antibody-drug conjugates. These advancements reflect a broader transition toward personalized, high-intensity regimens aimed at maximizing curative potential and long-term survival outcomes for patients.