Association of Underweight, Sarcopenia, and Cancer Cachexia with Survival Outcomes in Hypopharyngeal Cancer...

Objectives: This study investigates the association of pretreatment underweight, sarcopenia, and cancer cachexia with survival outcome in hypopharyngeal cancer (HPC) radiotherapy. Methods: This retrospective observational study analyzed 167 patients with newly diagnosed HPC treated with definitive radiotherapy. The definitions of underweight, sarcopenia, and cancer cachexia are based on the international consensus of the European Palliative Care Research Collaborative. Underweight and sarcopenia were analyzed in all 167 patients, while cachexia analyses were restricted to the 117 patients for whom pretreatment weight-loss data were available. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test, and subsequently analyzed using multivariate Cox proportional hazards models. Results: The median follow-up period was 28 months. Cachexia analyses were restricted to the 117 patients for whom pretreatment weight-loss data were available; of these, 45 (38%) met criteria for cancer cachexia. Patients with underweight (n = 76, 46%) or cancer cachexia had significantly lower locoregional control, disease-free survival, and overall survival compared to those not underweight and without cachexia, respectively, whereas there was no difference in any outcome between patients with sarcopenia (n = 54, 32%) and those without. Given the definitional overlap among underweight, sarcopenia, and cachexia, these three variables were entered into the multivariate analysis separately-which included age, sex, performance status, double cancer, T-classification, N-classification, chemotherapy administration, treatment era, and radiation dose-confirming that underweight and cancer cachexia remained independently associated with worse LRC, DFS, and OS. In the fully adjusted multivariate Cox proportional hazards models, the hazard ratios for mortality risk were 1.9 (95% confidence interval [CI], 1.1-3.4; p = 0.030) and 2.0 (95% CI, 1.1-3.8; p = 0.032) for patients with underweight or cancer cachexia, respectively. Conclusions: Pretreatment underweight and cancer cachexia negatively impact survival outcomes, including locoregional control, in HPC radiotherapy. Prospective studies with standardized nutritional assessment protocols, pre-specified intervention arms, and sufficient sample sizes are essential to validate these findings and to establish the clinical benefit of pre-treatment nutritional optimization in this patient population.