Development and Validation of a General Clinical Model for Predicting Neoadjuvant Chemotherapy Efficacy in Locally Advanced Gastric Cancer: Evidence from Meta-Analysis and Real-World Study

Background Neoadjuvant chemotherapy (NCT) is a cornerstone treatment for locally advanced gastric cancer (LAGC), yet patient responses vary significantly. This study aimed to develop and validate a general clinical model to predict NCT efficacy in LAGC patients. Methods A systematic review and meta-analysis were performed to identify independent clinical features associated with NCT efficacy. Using β coefficients, a risk score-based predictive model was constructed. Model performance was validated in 3 real-world cohorts using Area Under Curve (AUC) metrics. Prognostic utility was analyzed via Kaplan-Meier analysis. Additionally, an online NCT response prediction calculator was developed using R Shiny . Results A total of 4,014 patients from 25 high-quality cohort studies were included in the meta-analysis. Nine clinical features—CEA, tumor location, Lauren classification, histological grade, depth of invasion, lymph node metastasis, clinical stage, HER-2 status (IHC score), and Ki67—were incorporated into the final prediction model for NCT efficacy in LAGC. The present model demonstrated robust predictive performance, with AUCs of 0.760 (95% CI: 0.725–0.795), 0.786 (95% CI: 0.691–0.880), and 0.796 (95% CI: 0.718–0.875) across validation cohorts. NCT response was stratified into 4 levels based on risk scores, with increasing risk levels correlated with a progressive decline in treatment efficacy and poorer prognosis ( P <  0.001). The response rates in low-risk groups were 2.44- and 3.96-fold higher than those in high-risk and very high-risk groups, respectively. Conclusions This study establishes a robust and validated clinical model for predicting NCT efficacy and prognosis in LAGC patients. The accompanying online calculator provides a practical tool for personalized treatment planning. Future efforts will focus on expanding validation cohorts and refining the model to further optimize therapeutic decision-making for LAGC patients undergoing NCT. Trial registration: The protocol for the systematic review and meta-analysis was prospectively registered on PROSPERO (CRD42023483908) on March 12, 2023, prior to data collection. The validation cohorts (Cohorts 1–3) were derived from retrospective real-world data. As this study analyzed existing clinical records without prospective intervention, trial registration was not required for these cohorts.