Abstract
While immune checkpoint inhibitors have revolutionized small cell lung carcinoma (SCLC) management, clinical benefits remain restricted to a subset of patients. This study investigates baseline biomarkers for predicting outcomes in unresectable SCLC patients receiving first-line chemoimmunotherapy with or without radiotherapy. We retrospectively analyzed treatment-naïve, unresectable SCLC patients undergoing first-line chemoimmunotherapy at Peking University Cancer Hospital (between June 2020 and November 2022). Clinicopathological parameters, pretreatment hematologic indices, and immunohistochemical profiles (ASCL1, NEUROD1, POU2F3, YAP1, PD-L1, CD8, MHC-I, and Rb) were correlated with survival outcomes using Cox proportional hazards models. Composite biomarker strategies were evaluated for therapeutic stratification. A total of 143 SCLC patients were included (LS=41, ES=102). The SCLC-A subtype demonstrated optimal median overall survival (OS) than other subtypes (18 months vs. 11 months, P = 0.02), and SCLC-P patients exhibited poorer prognosis than NE phenotypes (SCLC-A, SCLC-N, SCLC-AN). Multivariate analysis identified VALSG stage (P = 0.02) and bone metastases (P = 0.045) as independent OS predictors in the entire cohort. Patients stratified by ASCL1/INSM1 positivity and NLR thresholds showed markedly divergent outcomes, with ASCL1+/NLRlow group and or INSM1+/NLRlow group achieving superior OS in the overall cohort, LS-SCLC, and ES-SCLC. The ASCL1/INSM1-NLR composite biomarker stratifies survival outcomes for unresectable SCLC patients treated with first-line chemoimmunotherapy with or without radiotherapy. Prospective multicenter validation is required.