RATIONALE AND OBJECTIVES: Immunotherapy combined with chemotherapy has improved outcomes for some esophageal squamous cell carcinoma (ESCC) patients, but accurate pre-treatment risk stratification remains a critical gap. This study constructed a deep learning (DL) model to predict survival outcomes in ESCC patients receiving immunotherapy combined with chemotherapy. MATERIALS AND METHODS: A DL model was developed to predict survival outcomes in ESCC patients receiving immunotherapy and chemotherapy. Retrospective data from 482 patients across three institutions were split into training (N=322), internal test (N=79), and external test (N=81) sets. Unenhanced computed tomography (CT) scans were processed to analyze tumor and peritumoral regions. The model evaluated multiple input configurations: original tumor regions of interest (ROIs), ROI subregions, and ROIs expanded by 1 and 3 pixels. Performance was assessed using Harrell's C-index and receiver operating characteristic (ROC) curves. A multimodal model combined DL-derived risk scores with five key clinical and laboratory features. The Shapley Additive Explanations (SHAP) method elucidated the contribution of individual features to model predictions. RESULTS: The DL model with 1-pixel peritumoral expansion achieved the best accuracy, yielding a C-index of 0.75 for the internal test set and 0.60 for the external test set. Hazard ratios for high-risk patients were 1.82 (95% CI: 1.19-2.46
P=0.02) in internal test set. The multimodal model achieved C-indices of 0.74 and 0.61 for internal and external test sets, respectively. Kaplan-Meier analysis revealed significant survival differences between high- and low-risk groups (P<
0.05). SHAP analysis identified tumor response, risk score, and age as critical contributors to predictions. CONCLUSION: This DL model demonstrates efficacy in stratifying ESCC patients by survival risk, particularly when integrating peritumoral imaging and clinical features. The model could serve as a valuable pre-treatment tool to facilitate the implementation of personalized treatment strategies for ESCC patients undergoing immunotherapy and chemotherapy.