Pre-screening value of serum albumin and the glucose-lymphocyte ratio as the "transport-activation" effectors of immune checkpoint inhibitors in small cell lung cancer.

Background: Small cell lung cancer (SCLC), a therapy-resistant neuroendocrine carcinoma, shows variable responses to immune checkpoint inhibitors (ICIs) and chemotherapy regimens. This study aimed to evaluate the pre-screening utility of peripheral blood serum albumin (ALB) and the glucose-to-lymphocyte ratio (GLR) as biomarkers for identifying populations of SCLC patients likely to benefit from ICIs. Methods: A retrospective cohort of SCLC patients receiving ICIs between 2018 and 2023 was analyzed. The optimal prognostic thresholds for ALB and the GLR were determined using maximally selected rank statistics. The survival outcomes were assessed via Kaplan-Meier analysis and Cox regression. A propensity score matching (PSM) analysis adjusted for confounders was performed. A prognostic nomogram integrating ALB, the GLR, and clinical variables was developed. Model performance was assessed using the concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curves. Results: Among 126 eligible patients, 93 (73.8%) had extensive-stage SCLC at diagnosis, and 33 (26.2%) presented with brain metastasis. The optimal cut-off values of ALB and the GLR for predicting overall survival (OS) were 40.9 g/L and 5.02, respectively. Multivariable Cox regression identified ALB [hazard ratio (HR) =0.415, 95% confidence interval (CI): 0.247-0.696] and GLR (HR =0.560, 95% CI: 0.315-0.994) as independent prognostic factors favoring longer OS, with ALB showing stronger protective association. Patients with both high ALB and a high GLR demonstrated the most favorable OS among the four subgroups (P<0.001). The prognostic model, which incorporated ALB, the GLR, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and clinical stage, had a C-index of 0.752 [area under the curve (AUC) values: 0.804 at 12 months and 0.781 at 24 months]. Conclusions: Pre-treatment serum ALB and the GLR represent cost-effective, readily accessible biomarkers for stratifying SCLC patients who may derive survival benefits from ICI-based regimens. These findings warrant validation in prospective multicenter studies.