Objective To investigate the effect of interaction between body mass index (BMI) and gender on the survival of advanced gastric cancer after immunotherapy.

Methods The retrospective cohort study was conducted. The clinicopathological data of 317 patients with advanced gastric cancer who were admitted to the Nanfang Hospital, Southern Medical University from November 2019 to October 2023 were collected. There were 205 males and 112 females, aged 56 (range, 21-79)years. All 317 patients were divided into three groups based on BMI of patients, including 58 cases with BMI < 18.5 kg/m² were classified as the low body mass group, 183 cases with BMI 18.5-24.0 kg/m² were classified as the normal body mass group, and 76 cases with BMI > 24.0 kg/m² were classified as the overweight or obese group. Patients included in the study were treated with a programmed death-ligand 1 (PD-L1) based immunotherapy regimen for 3 cycles based on their specific conditions, and further decision was made whether to undergo radical surgery or continue comprehensive treatment after evaluating the efficacy. Observation indicators: (1) clinicopathological characteristics of patients; (2) follow-up and mortality status; (3) analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Comparison of measurement data with normal distribution among groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test. Comparison of count data among groups was conducted using the chi-square test. The Cox proportional hazard model was used for univariate and multivariate analyses. Nonlinear trend was analyzed using the restricted cubic spline (RCS) curve, and trend and correction graphs were created using the rcssci package (v1.0).

Results (1) Clinicopathological characteristics of patients. There was no significant difference in gender, age, Borrmann classification, Lauren classification, combined positive score of PD-L1, expression of human epidermal growth factor receptor 2, Epstein-Barr virus infection, carcino-embryonic antigen, CA19-9, CA72-4, alpha-fetoprotein, conversion surgery among the 3 groups of patients (P > 0.05), and there was a significant difference in mismatch repair combined with micro-satellite stability among the 3 groups of patients (P < 0.05). (2) Follow-up and mortality status. Of the 317 patients, 316 cases completed follow-up and 1 case in the overweight or obese group was lost to follow-up. The follow-up time of the 316 cases was 13.8(range, 0.9-48.2)months. During the follow-up, the number of death in the low body mass group, normal body mass group and overweight or obese group were 27, 70 and 31, respectively. (3) Analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Results of multivariate analysis showed that gender and BMI were independent factors affecting survival of patients with advanced gastric cancer after immunotherapy (hazard ratio=0.066, 0.922, 95% confidence interval as 0.005-0.846, 0.855-0.994, P < 0.05). Results of further analysis showed that the interaction between BMI and gender was an independent factor affecting survival of patients with advanced gastric cancer after immuno-therapy (hazard ratio=1.152, 95% confidence interval as 1.024-1.296, P < 0.05). Results of Cox regre-ssion analysis based on different gender showed that took patients of the normal body mass group as a reference, the male patients of the low body mass group had a significantly increased risk of death, showing a significant statistically difference (hazard ratio=1.809, 95% confidence interval as 1.037-3.155, P < 0.05). Results of RCS curve analysis showed that there was a non-linear correlation between BMI and survival of patients with advanced gastric cancer after immunotherapy (P < 0.05). Results of corrected RCS curve analysis using the rcssci package showed that there was a U-shaped relationship between BMI and survival of patients with advanced gastric cancer after immuno-therapy (P < 0.05), with the optimal cut-off value of BMI as 22.2 kg/m². Results of RCS curve analysis based on different gender showed that there was a U-shaped relationship between BMI and survival of male patients with advanced gastric cancer after immunotherapy (P < 0.05), with the optimal cut-off value of BMI as 22.7 kg/m².

Conclusions Gender, BMI and the interaction between BMI and gender are independent factors affecting survival of patients with advanced gastric cancer after immuno-therapy. There is a U-shaped relationship between BMI and survival of patients, with the optimal cut-off value of BMI as 22.2 kg/m², and there is a U-shaped relationship between BMI and survival of male patients, with the optimal cut-off value of BMI as 22.7 kg/m².