Published online Aug 7, 2026. doi: 10.3748/wjg.119809
Revised: February 25, 2026
Accepted: March 27, 2026
Published online: August 7, 2026
Processing time: 161 Days and 14.7 Hours
Advanced gastric cancer (GC) remains a major cause of cancer-related mortality worldwide. Perioperative chemotherapy has been established as a standard treatment strategy to improve resectability and survival outcomes. Recently, the incorporation of immune checkpoint inhibitors into chemotherapy regimens has demonstrated promising survival benefits in advanced and metastatic settings. However, real-world evidence comparing immunochemotherapy with intensified chemotherapy regimens in the perioperative context remains limited, and the prognostic factors influencing progression-free survival (PFS) in this population are not fully understood.
To compare the efficacy and safety of oxaliplatin plus S-1 combined with sin
A total of 323 patients with advanced GC who received neoadjuvant chemotherapy followed by standard D2 radical gastrectomy were retrospectively analyzed. Among them, 101 patients were treated with SOX + XDL, 148 with P-SOX, and 74 with CAPOX. By using the sample function in R software, all patients were randomly assigned to a training set and a validation set, which were used for model development and validation, respectively. Short-term efficacy, long-term outcomes, and treatment-related adverse events were compared among the three groups. In addition, clinical factors associated with PFS were further investigated.
Based on the tumor regression grade, compared with the P-SOX and CAPOX groups, the SOX + XDL group achieved a significantly greater pathological response (85.15% vs 72.30% vs 59.46%, P < 0.001). According to the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, the objective response rate was numerically higher in the SOX + XDL group (68.32%) than in the P-SOX (60.14%) and CAPOX (55.41%) groups, but the difference was not statistically significant (P = 0.196). Kaplan-Meier analysis revealed significant differences in overall survival (OS) and PFS among the three regimens. Patients treated with SOX + XDL had better OS (log-rank P = 0.004) and longer PFS (log-rank P = 0.026) than did those treated with P-SOX or CAPOX. All regimens were generally well tolerated, with predominantly mild to moderate adverse events. No significant differences in hematologic toxicity or liver function abnormalities were detected among the groups (all P > 0.05). However, alopecia occurred more frequently in the P-SOX and CAPOX groups than in the SOX + XDL group (P = 0.002).
Compared with the other regimens, the SOX + XDL regimen showed superior short-term efficacy and improved survival outcomes, with better OS and PFS. Favorable treatment response, smaller tumor size (≤ 2 cm), earlier clinical tumor-node-metastasis stage, and well-differentiated tumors were associated with better prognosis in patients with advanced GC.
Core Tip: This real-world study systematically compared perioperative oxaliplatin plus S-1 combined with sintilimab, nab-paclitaxel plus oxaliplatin and S-1, and capecitabine plus oxaliplatin regimens in patients with advanced gastric cancer, focusing on treatment efficacy, survival outcomes, and safety. Beyond conventional survival analyses, a prognostic model was developed and validated to stratify progression-free survival risk using readily available clinicopathological and treatment response variables. The findings demonstrate that oxaliplatin plus S-1 combined with sintilimab is associated with favorable survival outcomes with manageable toxicity, and the proposed nomogram provides a practical tool for individualized risk assessment and treatment decision-making in perioperative advanced gastric cancer.