Longitudinal evaluation of C3- and L3-derived skeletal muscle indices for cancer-specific survival and recurrence endpoints in radiotherapy-treated head and neck cancer.

PURPOSE: To determine whether longitudinal skeletal muscle assessment improves prognostic evaluation for head and neck cancer-specific survival (HNC-Surv) and recurrence outcomes in radiotherapy-treated patients, and secondarily to compare prognostic performance of C3- versus L3-derived skeletal muscle indices. METHODS: This prognostic study included 206 patients with HNC treated with curative-intent radiotherapy. Skeletal muscle index (SMI) was assessed at baseline and post-treatment imaging, and longitudinal metrics (percentage change and change rate) were calculated. Fine-Gray competing-risk regression was used for HNC-Surv, and Cox regression for locoregional recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS). Discrimination was evaluated using time-dependent ROC analysis and compared using the DeLong test. RESULTS: Over a median follow-up of 5.6 years, 68 deaths occurred, including 52 HNC-related deaths; 59 patients (29%) developed recurrence. Post-treatment SMI was the most consistent independent prognostic factor across outcomes. In the C3-based HNC-Surv model, SMI percentage change remained independently prognostic in addition to post-treatment SMI. Discrimination was similar between C3- and L3-based models for HNC-Surv (AUC 0.685 vs. 0.706; p = 0.738), LRFS (0.638 vs. 0.658; p = 0.778), and DRFS (0.640 vs. 0.660; p = 0.880). CONCLUSION: Longitudinal muscle assessment, particularly post-treatment SMI and, for HNC-Surv, C3 SMI percentage change, improves prognostic evaluation in radiotherapy-treated HNC. C3- and L3-based models show comparable discrimination, supporting the use of cervical-level metrics when abdominal imaging is unavailable.