Determinants of survival after neoadjuvant chemotherapy in resectable gastric cancer: adjuvant dose intensity, radiotherapy, and pathologic response.

[BACKGROUND] Neoadjuvant chemotherapy (NACT) is the standard of care for locally advanced gastric cancer, but adjuvant therapy is not tailored to pathological response and outcomes are poor. This study evaluated the impact of adjuvant chemotherapy (ACT) dose intensity, radiotherapy, and pathologic factors on disease-free survival (DFS) and overall survival (OS).

[METHODS] A total of 197 patients with locally-advanced gastric cancer treated with NACT followed by gastrectomy from seven cancer centers were analyzed. Clinical, surgical, and pathological data were extracted. ACT regimens, dose-reductions, and receiving radiotherapy were recorded. Primary outcomes were DFS and OS. Kaplan-Meier and Cox-models were used to identify predictors of survival.

[RESULTS] Most patients received FLOT (84.8%) as NACT and D2-lymphadenectomy. Full-dose ACT was delivered to 66.1%. At 24 months, DFS and OS were 77.1% and 84.1% with full-dose ACT versus 35.8% and 63.6% with reduced-dose ACT. Dose reduction independently increased recurrence risk (HR 4.73) and mortality (HR 2.84). Positive margins, higher ypT/ypNstage, <50% tumor-regression, lymphovascular and perineural invasion were associated with shorter DFS. Adjuvant radiotherapy did not significantly improve survival outcomes.

[CONCLUSIONS] Reduced-dose ACT after NACT and surgery was associated with inferior DFS and OS, indicating that maintaining full-dose adjuvant therapy is critical. These findings are limited by retrospective design; prospective response-adapted trials are needed.