Successful Conversion Surgery after S-1 plus oxaliplatin Plus Zolbetuximab for Initially Unresectable Gastric Cancer with Pancreatic Invasion: A Case Report.

INTRODUCTION: Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), has recently demonstrated significant survival benefits when combined with chemotherapy for advanced gastric cancer. However, evidence regarding conversion surgery following SOX plus zolbetuximab therapy remains extremely limited. CASE PRESENTATION: A 59-year-old woman presented with epigastric discomfort. Endoscopy revealed a depressed lesion in the lower gastric body, and biopsy confirmed signet-ring cell carcinoma. Imaging and diagnostic laparoscopy indicated Type 4 gastric cancer with pancreatic invasion (cT4b, cN0, cP0, cCY0, cM0, cStage IVA). The tumor was HER2-negative, mismatch-repair proficient, PD-L1 combined positive score <1, and strongly positive for CLDN18.2. The patient received 13 courses of SOX plus zolbetuximab, resulting in radiological downstaging (ycT4a, ycN0, ycM0, ycStage IIB). It was determined that an R0 resection was feasible, and total gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction was performed. Pathology revealed a minimal residual tumor (5 × 2 mm) with ypT2, ypN0, ypStage IB and a histological response of Grade 2b. R0 resection was achieved. The patient remains recurrence-free 7 months postoperatively. CONCLUSIONS: To our knowledge, this is the first published case describing successful conversion surgery following SOX plus zolbetuximab therapy. This case suggests that CLDN18.2-targeted therapy may facilitate curative resection in selected patients with initially unresectable gastric cancer.