Prognostic Value of Masseter Muscle Index, Masseter Radiodensity, and the Global Immune-Nutrition-Inflammation Index in Laryngeal Carcinoma Treated with Definitive Radiotherapy

Background: This retrospective study evaluated pretreatment masseter muscle index (MMI), masseter radiodensity (HUAC), and Global Immune–Nutrition–Inflammation Index (GINI) as prognostic markers in patients with laryngeal squamous cell carcinoma treated with definitive radiotherapy. Methods: MMI and HUAC were measured on simulation computed tomography, and GINI was calculated from pretreatment laboratory values. Biomarkers were analyzed continuously using Firth penalized Cox models adjusted for age, performance status, tumor site, and T and N categories. Nonlinearity was assessed using restricted cubic splines. Joint models and multiple imputation assessed robustness. HUAC associations were assessed over time. Exploratory cutoffs were derived using censoring-aware three-year time-dependent receiver operating characteristic analysis, with radiotherapy initiation as time zero. Results: Among 146 patients, 30 died and 48 experienced progression or death; GINI was available in 116. Each standard-deviation decrease in MMI was associated with worse overall survival (OS; adjusted hazard ratio 1.92, 95% confidence interval 1.21–3.05; p = 0.002) and progression-free survival (PFS; 1.91, 1.35–2.71; p < 0.001). These associations weakened after further adjustment for body mass index and concurrent systemic therapy. GINI findings were not robust in adjusted, joint, and missing-data analyses. Lower HUAC showed an exploratory association with poorer outcomes later in follow-up, based on few late events. Three-year OS/PFS estimates were 92.5%/81.1% versus 68.9%/59.5% for MMI > 2.830 versus ≤2.830 cm2/m2, and 90.2%/81.9% versus 45.1%/38.0% for GINI < 139.67 versus ≥139.67. The GINI cutoff was unstable, with a 95% bootstrap interval of 20.104–180.985. Conclusions: Lower MMI showed the most consistent prognostic association. This initial evaluation of GINI in laryngeal cancer supports further investigation of its prognostic potential. HUAC findings and cohort-derived cutoffs remain exploratory and require external validation.