Impact of body composition on prognosis, treatment toxicity, and surgical complications in locally advanced gastric cancer

Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the L3 vertebra is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced gastric cancer (LA-GC), stage IB – III, treated in four Portuguese hospitals, between January 2020 and December 2022. Skeletal muscle area was assessed on baseline CT at the L3 vertebra level, using Data Analysis Facilitation Suite (DAFS) software, and skeletal muscle index (SMI) was calculated. Sarcopenia was defined as an SMI below sex specific mean. The primary objective was to evaluate the association of sarcopenia with FLOT Chemotherapy Dose Limiting Toxicities (DLTs). Secondary objectives were to evaluate the association between sarcopenia and Postoperative Complications after gastrectomy, Relapse Free Survival (RFS) and Overall Survival (OS). Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49,6 cm²/m² in males and 40,9 cm²/ m² in females. SMI correlated positively, though moderately, with BMI (p , 0.01; r = 0.424). Sarcopenia was associated with higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15-5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11-4.21). Although sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30 months follow up, a numerical difference was observed (64% vs 56% of patients did not relapse and 74% vs 63% were alive, for non sarcopenic vs sarcopenic patients). Conclusions: Sarcopenia significantly increased the risk of chemotherapy toxicity and postoperative complications in LA-GC. The effect of sarcopenia on OS and RFS was not statistically significant in this locally advanced disease cohort, possibly because surgical intervention modifies the disease trajectory. The lack of standardized CT based sarcopenia cut-offs remains a major barrier to clinical implementation. Nevertheless, early detection of sarcopenia using CT imaging may represent a valuable and precise tool to identify patients requiring closer monitoring, chemotherapy dose optimization, and early referral for multimodal interventions, including pharmacologic therapy, structured exercise programs, and personalized nutritional support. Research Sponsor: None.