Frontiers in oncology · 2026
An integrated body composition- immunonutritional signature for predicting immunotherapy response and prognosis in gastric cancer: a multicenter retrospective cohort study.
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Li Fang, Zheng Tao, Guo Honghai, Yang Peigang, Meng Ning, Li Xiaolong, Guo Zhenjiang, Tian Yuan, Zhao Qun
Аннотация
BACKGROUND: Response to neoadjuvant PD-1 inhibitor plus chemotherapy in locally advanced esophagogastric adenocarcinoma varies widely, and tumor biomarkers alone do not fully explain the variation. We developed an integrated Body Composition and Immunonutritional Signature (BCIS) from pretreatment CT body composition and routine blood markers, and tested whether it predicts pathological response, immune-related adverse events (irAEs), and survival.
METHODS: From four tertiary hospitals in Hebei Province, China, we enrolled 720 patients with histologically confirmed gastric or gastroesophageal junction (Siewert II/III) adenocarcinoma treated between 2019 and 2023 with neoadjuvant PD-1 inhibitor plus SOX or XELOX followed by D2 gastrectomy. BCIS was a 0-10 additive score from ten prespecified adverse host features. Analyses included logistic regression, restricted cubic spline (RCS) modeling, multivariable Cox regression, DeLong tests for nested AUC comparisons, decision-curve analysis, eleven sensitivity scenarios, and collinearity checks by Spearman correlation and variance inflation factors.
RESULTS: BCIS classified 243 (33.8%) patients as favorable, 303 (42.1%) as intermediate, and 174 (24.2%) as unfavorable. Major pathological response (MPR) rates dropped sharply across strata (64.2%, 39.6%, 21.8%; P-trend<0.001). After adjusting for age, sex, cT/cN, PD-L1 CPS, MMR status, EGJ origin, and regimen, every BCIS point cut the odds of MPR by roughly 40% (adjusted OR = 0.61, 95% CI 0.55-0.68, P<0.001) and pCR by close to half (adjusted OR = 0.55, 95% CI 0.46-0.66, P<0.001). RCS modeling flagged CRP and CAR as nonlinear; BCIS itself was strictly linear. Adding BCIS to a clinical baseline lifted overall AUC for MPR from 0.597 to 0.710 (DeLong P<0.001) and external AUC from 0.588 to 0.704. At 42.5 months' median follow-up, each BCIS point raised the hazard of progression by 53% (adjusted HR = 1.53, 95% CI 1.44-1.63) and of death by 38% (adjusted HR = 1.38, 95% CI 1.29-1.47; both P<0.001). Direction of effect held across every prespecified subgroup (P-interaction>0.10 throughout) and all eleven sensitivity scenarios.
CONCLUSIONS: BCIS is independently associated with pathological response and survival under neoadjuvant PD-1-based immunochemotherapy and adds discrimination beyond tumor-centered biomarkers and clinical staging. Because every component comes from routine pretreatment workup at no extra cost, BCIS could feasibly inform prehabilitation, toxicity surveillance, and shared decision-making.
METHODS: From four tertiary hospitals in Hebei Province, China, we enrolled 720 patients with histologically confirmed gastric or gastroesophageal junction (Siewert II/III) adenocarcinoma treated between 2019 and 2023 with neoadjuvant PD-1 inhibitor plus SOX or XELOX followed by D2 gastrectomy. BCIS was a 0-10 additive score from ten prespecified adverse host features. Analyses included logistic regression, restricted cubic spline (RCS) modeling, multivariable Cox regression, DeLong tests for nested AUC comparisons, decision-curve analysis, eleven sensitivity scenarios, and collinearity checks by Spearman correlation and variance inflation factors.
RESULTS: BCIS classified 243 (33.8%) patients as favorable, 303 (42.1%) as intermediate, and 174 (24.2%) as unfavorable. Major pathological response (MPR) rates dropped sharply across strata (64.2%, 39.6%, 21.8%; P-trend<0.001). After adjusting for age, sex, cT/cN, PD-L1 CPS, MMR status, EGJ origin, and regimen, every BCIS point cut the odds of MPR by roughly 40% (adjusted OR = 0.61, 95% CI 0.55-0.68, P<0.001) and pCR by close to half (adjusted OR = 0.55, 95% CI 0.46-0.66, P<0.001). RCS modeling flagged CRP and CAR as nonlinear; BCIS itself was strictly linear. Adding BCIS to a clinical baseline lifted overall AUC for MPR from 0.597 to 0.710 (DeLong P<0.001) and external AUC from 0.588 to 0.704. At 42.5 months' median follow-up, each BCIS point raised the hazard of progression by 53% (adjusted HR = 1.53, 95% CI 1.44-1.63) and of death by 38% (adjusted HR = 1.38, 95% CI 1.29-1.47; both P<0.001). Direction of effect held across every prespecified subgroup (P-interaction>0.10 throughout) and all eleven sensitivity scenarios.
CONCLUSIONS: BCIS is independently associated with pathological response and survival under neoadjuvant PD-1-based immunochemotherapy and adds discrimination beyond tumor-centered biomarkers and clinical staging. Because every component comes from routine pretreatment workup at no extra cost, BCIS could feasibly inform prehabilitation, toxicity surveillance, and shared decision-making.