Conversion surgery following nivolumab plus SOX therapy for unresectable advanced esophagogastric junction cancer:...

Nivolumab plus SOX chemotherapy has emerged as an effective first-line treatment for HER2-negative unresectable advanced gastric cancer, and conversion surgery following favorable treatment response is increasingly considered as a potential curative strategy. Here, we report two cases of HER2-negative esophagogastric junction cancer initially diagnosed as unresectable. Case 1 presented with splenic metastasis and tumor thrombus in the splenic vein, and Case 2 with multiple liver metastases and extensive lymph node involvement. Both cases were classified as cStage IVB. After receiving nivolumab plus SOX chemotherapy, they demonstrated significant tumor shrinkage and disappearance of distant metastases, making CS feasible. Robotic gastrectomy was successfully performed in both cases. Pathological examination revealed tumor downstaging in both, while Case 1 showed neuroendocrine carcinoma and Case 2 revealed mucinous and signet-ring cell carcinoma components. Genomic profiling before and after treatment demonstrated persistence of TP53 mutation in Case 1 and SYNE1 mutation in Case 2, with no significant changes in allele frequency. These findings suggest that while therapy-sensitive clones were eliminated, resistant clones remained. Nivolumab plus SOX chemotherapy may help make conversion surgery possible in patients with HER2-negative advanced gastric cancer. Analyzing treatment-resistant tumor characteristics pathologically and genomically could support the development of personalized therapies.

The online version contains supplementary material available at 10.1007/s13691-025-00838-y.