Circulating cytokines and inflammatory indices associate with prognosis and toxicities in first line extensive stage small cell lung cancer immunochemotherapy

Although chemoimmunotherapy has been the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), survival benefits remain unsatisfactory and effective biomarkers are lacking. Circulating cytokines and inflammatory indices provide non-invasive, dynamic monitoring advantages. However, their prognostic value and associations with immune-related adverse events (irAEs) remain unclear. This study retrospectively analyzed a two-center cohort of 96 ES-SCLC patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy. High baseline IFN-γ and TNF-α were associated with shorter progression-free survival (PFS), while high IL-5 was associated with longer PFS. Liver metastasis, high baseline SIRI, IFN-γ, and RDW were associated with shorter overall survival (OS). Notably, post-treatment elevation of IFN-γ was associated with longer survival, which was contrary to the baseline status. The nomograms exhibited acceptable predictive performance, with AUCs of 0.74 for 12-month PFS and 0.89 for 24-month OS. Thirty-three patients experienced irAEs. Exploratory analyses showed that high baseline IL-4, IL-1β, and PLR were associated with increased irAE risk. In contrast, high TNF-α and NLR were associated with reduced risk. Interestingly, post-treatment elevation of TNF-α predicted the occurrence of irAEs. These findings suggest that circulating cytokines and inflammatory indices may serve as non-invasive biomarkers for both prognosis and toxicities in ES-SCLC. This study further highlights the potential value of dynamic monitoring and provides a predictive tool to assist clinicians in optimizing individualized treatment strategies.