AUTHOR=Zhang Guisheng , Gong Bingxin , Guo Yusheng , Lou Jie , Peng Ying , Cai Siqian , Fu Zhichao , Xu Yuanji , Yang Lian 

TITLE=The crossroads of inflammation and nutrition: predicting neoadjuvant immunochemotherapy efficacy in esophageal squamous cell carcinoma patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1663268

DOI=10.3389/fimmu.2025.1663268

ISSN=1664-3224

ABSTRACT=BackgroundNeoadjuvant immunochemotherapy (nICT) improves outcomes in esophageal squamous cell carcinoma (ESCC); however, patient response heterogeneity limits its clinical benefit. The aim of this study was to investigate the predictive value of the systemic immune-inflammation index and prognostic nutritional index score (SII-PNI score), which is jointly constructed from the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), for pathological complete response (pCR) and survival outcomes.MethodsThis retrospective study included patients with stage II to IV ESCC who received nICT therapy at Wuhan Union Hospital (WHUH), Fujian Cancer Hospital (FJCH), and 900th Hospital of the Joint Service Support Force of the People’s Liberation Army of China (900th Hospital). The predictive performance of SII-PNI score was validated using receiver operating characteristic (ROC) curves. Multivariate logistic regression confirmed SII-PNI score as an independent predictor of pCR. Additionally, Cox regression model and Kaplan-Meier survival curves were employed to analyze disease-free Survival (DFS) and overall survival (OS).ResultsA total of 345 patients were included, stratified into 0-score (n = 70), 1-score (n = 149), and 2-score (n = 126) groups. The combined cohort (Combined from FJCH cohort, WHUH cohort, 900th Hospital cohort) area under the ROC curve (AUC) revealed that SII-PNI score (AUC = 0.803) outperformed SII (AUC = 0.679, DeLong’s test P < 0.001) and PNI (AUC = 0.667, DeLong’s test P < 0.001) in predicting pCR. Compared with 0-score patients, those with 1-score (odds ratio [OR] = 0.159, 95% confidence interval [CI]:0.080-0.319, P < 0.001) and 2-score (OR = 0.025, 95% CI:0.009-0.073, P < 0.001) had significantly lower pCR rates. The 2-score group showed had shorter of DFS (hazard ratio [HR] = 2.487, 95% CI:1.414-4.374, P = 0.002) and OS (HR = 4.473, 95% CI:2.138-9.357, P < 0.001) versus the 0-score group.ConclusionsThis study demonstrated for the first time that the SII-PNI score can be used as an independent predictor of pCR in patients with ESCC treated with nICT and has prognostic stratification value. This suggests that it has the potential to be a pre-treatment assessment tool for evaluating treatment response and prognosis before nICT treatment.