Abstract
BACKGROUND: Gastric cancer remains a leading cause of cancer-related mortality. While immune checkpoint inhibitors (ICIs) have emerged as promising therapies, their efficacy is hindered by the lack of robust patient-centric biomarkers. Obesity, traditionally linked to cancer risk, paradoxically correlates with improved immunotherapy responses in some cancers, termed the "obesity paradox". However, traditional measurements like body mass index (BMI) may not fully capture metabolic-immune interactions. This study evaluates the predictive significance of lipid accumulation product (LAP) and visceral adiposity index (VAI), two metabolic indices, in gastric cancer patients receiving programmed death receptor-1 (PD-1) inhibitors. METHODS: A retrospective study was conducted on 146 gastric adenocarcinoma patients (stage III: n = 61; stage IV: n = 85) treated with PD-1 inhibitors at Wuhan Union Hospital from September 5, 2020, to October 15, 2023. We evaluated two metabolic obesity indices: LAP and VAI. LAP was calculated using waist circumference (WC) and triglyceride (TG) levels, while VAI incorporated WC, BMI, TG, and high-density lipoprotein cholesterol (HDL-C), with gender-specific formulas. Measurements followed standardized protocols with biochemical assays. Patients were stratified into high/low LAP and VAI groups using X-tile-derived optimal cut-offs. Survival outcomes were analyzed through Kaplan-Meier curves with log-rank testing. Prognostic factors were identified via univariate and multivariate Cox regression analyses. Subgroup analyses further validated the model's robustness across clinical strata. Predictive accuracy was quantified using time-dependent receiver operating characteristic (ROC) curves, while clinical utility was assessed through decision curve analysis (DCA). RESULTS: Patients with high LAP and high VAI had significantly better PFS and OS than those with lower indices (log-rank test, P < 0.001). Multivariate Cox regression analysis confirmed that high LAP (PFS: HR: 0.403, 95% CI: 0.233- 0.698, P = 0.001; OS: HR: 0.287, 95% CI: 0.153-0.541, P < 0.001) and high VAI (PFS: HR: 0.370, 95% CI: 0.214-0.642, P < 0.001; OS: HR: 0.300, 95% CI: 0.164-0.548, P < 0.001) were independent protective factors for both PFS and OS. CONCLUSION: LAP and VAI may serve as independent predictors of long-term survival in gastric cancer patients undergoing immunotherapy.