Spleen volume change as a prognostic and immunologic imaging biomarker in extensive-stage small-cell lung cancer receiving chemo-immunotherapy.

BACKGROUND: The spleen, the largest secondary lymphoid organ, plays an essential role in systemic immune regulation. Its function in tumor progression and treatment response has gained increasing attention. OBJECTIVES: This study aimed to evaluate the prognostic value of spleen volume (SV) change in patients with extensive-stage small-cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy (CIT) and to explore its associations with tumor-infiltrating lymphocytes (TILs) and peripheral immune parameters. DESIGN: A single-center retrospective cohort study. METHODS: A total of 292 ES-SCLC patients who received first-line CIT were retrospectively analyzed. SV was measured on baseline and post-treatment CT scans, and the relative change was used to classify patients into increased or decreased SV groups. Cox proportional hazards regression models were used to assess the effects of SV metrics, immune-related indices, and clinicodemographic factors on overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR) differences were tested using the chi-square test, and immune parameters were compared using Wilcoxon rank-sum tests and correlation analyses. RESULTS: Multivariate analysis identified increased SV after CIT as an independent adverse prognostic factor for both OS (hazard ratio (HR) = 1.561, 95% confidence interval (CI), 1.193-2.041, p = 0.001) and PFS (HR = 1.411, 95% CI, 1.106-1.800, p = 0.006). Patients with increased SV exhibited significantly shorter OS and PFS and a lower ORR (all p < 0.005). Increased SV was also associated with markedly lower total, CD4+, and CD8+ TIL densities and, at the systemic level, lower absolute lymphocyte count (ALC), and higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (all p < 0.0001), indicating both local and systemic immune suppression. CONCLUSION: SV change reflects both local and systemic immune remodeling during CIT in ES-SCLC. As a noninvasive and measurable imaging biomarker, SV change holds translational potential for immune monitoring and treatment response assessment.