The risk of developing esophageal cancer is between 30 and 125 times higher in patients with Barrett's esophagus. Interleukins can aid in the development of a tumor-directed immune response to improve immunotherapy. Drs. David H. Ilson and Nataliya Uboha highlight the final OS results of the phase 3 SPOTLIGHT study. Claudin 18 isoform 2 is an emerging therapeutic target in gastric and gastroesophageal cancers. qFME with oral administration of bevacizumab-800CW and cetuximab-800CW is feasible, and can shorten procedure time. Dr. Eng opines on how the ESOPEC study will alter the treatment paradigm for patients with esophageal/GEJ adenocarcinoma. The trio pondered the evolving landscape of upper GI cancer treatments, particularly in localized and advanced stages. Switch maintenance may extend the benefits of an initial treatment strategy and can delay clinical deterioration. Drs. Filippo Pietrantonio and Nataliya Uboha break down the results of the phase 3 ARMANI trial. The primary end point of the analysis was OS, and secondary end points included PFS and ORR. Patients with mPR experienced improved PFS and OS with pembrolizumab plus chemotherapy over placebo plus chemotherapy. Drs. Wainberg and Uboha highlight exciting developments set to occur at the ASCO Meeting, including ESOPEC and ARC-9. RELATIVITY-060 investigated the efficacy of first-line relatlimab and nivolumab with chemotherapy for gastric or GEJ cancers. Drs. Wainberg and Uboha discuss updated results from the FIGHT trial, noting improved OS in gastric cancer/GEJ cancer. Capecitabine was compared with XELOX and fluorouracil plus cisplatin. Dr. Kim provides an overview of the FDA approval of tislelizumab for the treatment of advanced, metastatic esophageal cancer. Dr. Sethi continues his comments on NER deficiency in gastric cancer cell lines in response to cisplatin treatment. Dr. Sethi discusses homologous recombination and nucleotide excision repair pathways in DNA repair for cancers. Matthew Strickland, MD, discusses the current management of defective mismatch repair in gastroesophageal adenocarcinoma. The effects of primary tumor and LN volume on clinical outcomes in ESCC following neoadjuvant CCRT and surgery are unknown.