Subcutaneous adipose tissue radiodensity as a prognostic marker in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors

Introduction: Radiodensity of subcutaneous adipose tissue (SAT), measurable on routine computed tomography (CT), may reflect metabolic status and cachexia, both of which influence cancer outcomes.However, its prognostic role in metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) remains unclear.This study aimed to evaluate the prognostic value of SAT radiodensity in this patient population.Material and methods: The retrospective analysis included 92 patients with stage IV NSCLC receiving ICI.Subcutaneous adipose tissue radiodensity (Hounsfield units) was measured from pre-treatment CT at the L3 level and categorized into quartiles.Kaplan-Meier analysis, log-rank test, and Cox proportional hazards models were used.Nonlinear associations were assessed using restricted cubic splines.Cox models were?adjusted for demographic, clinical, and treatment factors.A p-value < 0.05 was considered statistically significant.Results: Median overall survival for Q1, Q2, Q3, and Q4 was 13.4, 26.3, 18.4, and 14.2 months, respectively (log-rank p = 0.0226).Compared with Q1, Q2 showed a significantly reduced mortality risk across all models (fully adjusted hazard ratios = 0.32, 95% CI: 0.15-0.64,p = 0.002).Q3 and Q4 were not significantly different from Q1.Restricted cubic spline analysis revealed a mild U-shaped relationship (p for nonlinearity = 0.0094), with intermediate SAT density linked to best outcomes.Programmed death ligand 1 expression significantly modified the SAT-survival association (p for interaction < 0.0001).Conclusions: Moderate SAT radiodensity was associated with improved survival in metastatic NSCLC patients on ICI, potentially reflecting an optimal metabolic-immune balance.Subcutaneous adipose tissue density, easily obtained from routine imaging, warrants further prospective validation as a scalable prognostic biomarker.