Pre-radiotherapy cachexia is associated with treatment discontinuation in patients with head and neck squamous cell carcinoma receiving definitive radiotherapy.

Purpose: This study aimed to evaluate the association between pre-radiotherapy cachexia and treatment discontinuation, as well as other treatment-related outcomes, in patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive radiotherapy. Methods: This single-center retrospective cohort study consecutively enrolled M0 HNSCC patients who received definitive radiotherapy between July 2023 and December 2025. Cachexia was defined using an operational approach based on core diagnostic variables available in the medical records, informed by the Asian Working Group for Cachexia (AWGC) 2023 criteria. The primary outcome was treatment discontinuation. Secondary outcomes included unplanned radiotherapy interruptions, treatment-related adverse events, timing of acute radiation toxicity, timing of acute myelosuppression, nutritional risk during radiotherapy, and blood transfusion requirements. Logistic regression analyses were performed to assess the association between cachexia and treatment discontinuation. Results: A total of 137 patients were included, of whom 72 (52.6%) were classified as having cachexia. Treatment discontinuation was significantly higher in the cachexia group compared to the non-cachexia group (25.0% vs. 4.6%; P<0.001), and the incidence of treatment-related adverse events was also higher (97.2% vs. 78.5%; P<0.001). The distribution of first documented acute radiation toxicity across fraction-based categories differed between groups (P = 0.037). No significant differences were observed in unplanned interruptions, timing of acute myelosuppression, nutritional risk, or transfusion requirements. In univariable logistic regression, cachexia was significantly associated with treatment discontinuation (OR = 6.89; 95% CI 1.92-24.67; P = 0.003). After adjustment for age, Eastern Cooperative Oncology Group (ECOG) performance status, and concurrent chemotherapy, cachexia remained significantly associated with treatment discontinuation (OR = 6.05; 95% CI, 1.63-22.49; P = 0.007). Sensitivity analysis using Firth's penalized logistic regression yielded consistent results. Conclusions: In M0 HNSCC patients receiving definitive radiotherapy, pre-radiotherapy cachexia is significantly associated with treatment discontinuation and is accompanied by a higher incidence of treatment-related adverse events. Assessment of cachexia prior to radiotherapy may provide clinically relevant information on treatment tolerance and help identify patients at high risk of therapy discontinuation.