Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Sep 15, 2026; 18(9): 121765
Published online Sep 15, 2026. doi: 10.4251/wjgo.121765
Chemotherapy regimens with immunotherapy in advanced gastric cancer: A prognostic study using Cox modeling
Shao-Wei Jiang, Chen-Guang Zhang, Ke-Di Wang, Kun-Peng Shang, Peng-Jie Yu, Huan-Li Wang
Shao-Wei Jiang, Department of Radiation Oncology, Qinghai University Affiliated Hospital, Xining 810000, Qinghai Province, China
Chen-Guang Zhang, Department of Otolaryngology, Qinghai University Affiliated Hospital, Xining 810000, Qinghai Province, China
Ke-Di Wang, Kun-Peng Shang, Department of Gastrointestinal Oncology, Qinghai University Affiliated Hospital, Qinghai University, School of Clinical Medicine, Xining 810000, Qinghai Province, China
Peng-Jie Yu, Department of Gastrointestinal Oncology, Qinghai University Affiliated Hospital, Xining 810000, Qinghai Province, China
Huan-Li Wang, Qinghai University Affiliated Hospital Tumor Day Chemotherapy Center, Qinghai University Affiliated Hospital, Xining 810000, Qinghai Province, China
Co-first authors: Shao-Wei Jiang and Chen-Guang Zhang.
Co-corresponding authors: Peng-Jie Yu and Huan-Li Wang.
Author contributions: Jiang SW and Zhang CG were responsible for conceptualization, investigation, methodology, software, formal analysis, project administration, resources, data curation, writing original draft as co-first authors; Wang KD was responsible for software, writing original draft; Shang KP was responsible for data curation, writing original draft; Yu PJ and Wang HL were responsible for writing review editing, visualization, validation, funding acquisition, supervision as co-corresponding authors.
Supported by Qinghai Provincial Science and Technology Program, No. 2023-ZJ-787.
Institutional review board statement: This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Qinghai University Affiliated Hospital (No. SL-2022-035)
Informed consent statement: All participants provided informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request, subject to institutional and ethical regulations.
Corresponding author: Huan-Li Wang, Professor, Qinghai University Affiliated Hospital Tumor Day Chemotherapy Center, Qinghai University Affiliated Hospital, No. 29 Tongren Road, Chengxi District, Xining 810000, Qinghai Province, China.
229572196@qq.com
Received: April 1, 2026
Revised: April 20, 2026
Accepted: June 2, 2026
Published online: September 15, 2026
Processing time: 147 Days and 7.3 Hours
BACKGROUND
Locally advanced gastric cancer (GC) remains associated with a substantial risk of recurrence and poor long-term survival despite advances in multimodal treatment. Perioperative chemotherapy is a standard strategy, but the integration of immunotherapy into neoadjuvant treatment has shown promising potential. However, real-world comparative evidence regarding the efficacy and safety of different perioperative regimens remains limited.
AIM
To compare the efficacy and safety of three neoadjuvant treatment regimens – nab-paclitaxel plus oxaliplatin and S-1, oxaliplatin plus leucovorin and fluorouracil, and S-1 combined with sintilimab and oxaliplatin – in patients with locally advanced GC. Additionally, independent prognostic factors associated with progression-free survival (PFS) were identified, and a predictive model was developed to enable individualized risk stratification and prognostic assessment.
METHODS
This retrospective study included 298 patients with locally advanced GC who met the inclusion and exclusion criteria. Patients were randomly divided into a training set and a validation set at a 7:3 ratio using a fixed random seed. In the training set, least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation was used to select variables on the basis of the λ.1se criterion. Variables with nonzero coefficients were entered into a multivariable Cox proportional hazards model to identify independent factors associated with PFS, with hazard ratios (HRs) and 95%CIs calculated. The model was developed in the training set and validated in the validation set. Short-term efficacy, survival outcomes, and adverse events were compared among the three groups. Model performance was evaluated using receiver operating characteristic curves and calibration plots.
RESULTS
LASSO regression identified five variables with nonzero coefficients, including tumor differentiation, N stage, TNM stage, Response Evaluation Criteria in Solid Tumors 1.1 response, and tumor regression grade. Among these, TNM stage IIIC had the largest coefficient, indicating that it had the strongest impact on prognosis. These variables were subsequently included in a multivariable Cox proportional hazards model. The results demonstrated that poor differentiation (HR = 1.86; 95%CI: 1.19-2.91; P = 0.006), lymph node metastasis (HR = 1.69; 95%CI: 1.11-2.57; P = 0.013), and locally advanced clinical stage (cTNM stage IIIC; HR = 3.94; 95%CI: 2.47-6.28; P < 0.001) were independent risk factors for PFS in patients with GC. In contrast, a favorable response based on Response Evaluation Criteria in Solid Tumors 1.1 (HR = 0.65; 95%CI: 0.46-0.92; P = 0.016) and a lower tumor regression grade (HR = 0.56; 95%CI: 0.39-0.82; P = 0.003) were identified as protective factors.
CONCLUSION
This study demonstrated that compared with plus oxaliplatin and S-1 and oxaliplatin plus leucovorin and fluorouracil, the S-1 combined with sintilimab and oxaliplatin regimen resulted in a greater pathological response rate in patients with locally advanced GC and resulted in superior outcomes in terms of both PFS and overall survival, with an overall acceptable safety profile. The predictive model constructed based on LASSO and multivariable Cox regression exhibited good discrimination and calibration and may serve as a useful tool for post-treatment prognostic assessment and individualized risk stratification.
Core Tip: This study compares three commonly used neoadjuvant regimens (S-1 combined with oxaliplatin and sintilimab, plus oxaliplatin and S-1, and oxaliplatin plus leucovorin and fluorouracil) in advanced gastric cancer and demonstrates that the addition of a programmed cell death protein 1 inhibitor improves pathological response without increasing unacceptable toxicity. Furthermore, a prognostic model integrating treatment response (Response Evaluation Criteria in Solid Tumors 1.1 and tumor regression grade) with clinicopathological factors provides reliable prediction of progression-free survival, highlighting the value of response-based variables in individualized risk stratification.
