Baseline visceral adipose tissue radiodensity as biomarker of survival in advanced NSCLC treated with first-line single-agent immunotherapy.

INTRODUCTION: Body composition (BC) has emerged as a potential prognostic biomarker in oncology. In advanced non-small cell lung cancer (NSCLC), the impact of adipose tissue quality on outcomes with first-line immune checkpoint inhibitors (ICIs) remains unclear. We investigated the association between CT-derived BC parameters and survival in patients treated with single-agent immunotherapy. METHODS: We conducted a retrospective single-center cohort study including 140 patients with advanced NSCLC (PD-L1 ≥50%) treated with first-line single-agent ICIs. Baseline contrast-enhanced CT scans were analyzed using automated volumetric segmentation (L2-L4) to quantify visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle (SM) radiodensity. Associations with overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox models adjusted for age, sex, and ECOG PS, histology, disease stage, smoking history, PD-L1 expression. Sensitivity analysis was performed using L3 single-slice segmentation. RESULTS: In multivariable Cox models adjusted for clinical covariates, higher VAT radiodensity was independently associated with worse OS (HR 1.02 per 1-HU increase; 95% CI 1.01-1.03; p<0.001) and PFS (HR 1.02 per 1-HU increase; 95% CI 1.01-1.03; p<0.001). SAT radiodensity showed weaker associations with outcomes, whereas SM radiodensity was not prognostic. The addition of VAT radiodensity improved discrimination compared with clinical variables alone (ΔC-index +0.044 for OS and +0.037 for PFS). Findings were consistent in pembrolizumab-only and L3 single-slice analyses. CONCLUSION: Baseline VAT radiodensity emerged as an independent prognostic biomarker in advanced NSCLC treated with first-line immunotherapy. Adipose tissue quality may represent a relevant host-related factor associated with ICI outcomes.