Prospective Evaluation of Sarcopenia in Head and Neck Cancer Patients Treated with Radiotherapy or Radiochemotherapy

SIMPLE SUMMARY: Radiation therapy (RT) is a key treatment for head and neck squamous cell carcinoma (HNSCC) patients. RT generates acute toxicity and weight loss, especially when combined with chemotherapy. Frail patients (malnourished or with poor performance status) have poor outcomes and increased toxicity when treated by RT. Among non-frail patients, predicting RT outcome is a challenge. Loss of muscle mass, also known as sarcopenia, is associated with poor outcome in HNSCC patients treated by RT and chemotherapy, but the level of evidence remains weak. Conflicting results exist regarding the impact of sarcopenia on acute RT toxicity. This prospective study confirmed that in non-frail HNSCC patients baseline sarcopenia is frequent (37%) and is associated with decreased overall and disease-free survival, but not with acute toxicity. Interestingly, a worse impact of sarcopenia occurred despite optimal nutritional support and even when patients were treated by RT without chemotherapy. Sarcopenia should be regarded as an independent prognostic factor in that setting. ABSTRACT: Highlights: Sarcopenia is frequent in patients treated with radiation therapy (RT) or radiochemotherapy (RTCT) for head and neck squamous cell carcinomas. Sarcopenia is associated with poor disease-free survival and overall survival outcomes. Sarcopenia is not associated with a higher rate of treatment-related toxicity. Background: Sarcopenia occurs frequently with the diagnosis of head and neck squamous cell carcinoma (HNSCC). We aimed to assess the impact of sarcopenia on survival among HNSCC patients treated with radiotherapy (RT) or radiochemotherapy (RTCT). Methods: Patients treated between 2014 and 2018 by RT or RTCT with curative intent were prospectively included (NCT02900963). Optimal nutritional support follow-up, including weekly consultation with a dietician and an oncologist and daily weight monitoring, was performed. Sarcopenia was determined by measuring the skeletal muscles at the L3 vertebra on the planning CT scan for radiotherapy. For each treatment group (RT or RTCT), we assessed the prognostic value of sarcopenia for disease-free survival (DFS) and overall survival (OS) and its impact on treatment-related toxicity. Results: Two hundred forty-three HNSCC patients were included: 116 were treated by RT and 127 were treated by RTCT. Before radiotherapy, eight (3.3%) patients were considered malnourished according to albumin, whereas 88 (36.7%) patients were sarcopenic. Overall, sarcopenia was associated with OS and DFS in a multivariate analysis (HR 1.9 [1.1–3.25] and 1.7 [1.06–2.71], respectively). It was similar for patients treated with RT (HR 2.49 [1.26–4.9] for DFS and 2.24 [1.03–4.86] for OS), whereas for patients treated with RTCT sarcopenia was significantly associated with OS and DFS in univariate analysis only. Sarcopenia was not related to higher treatment-related toxicity. Conclusions: Pretherapeutic sarcopenia remains frequent and predicts OS and DFS for non-frail patients treated with curative intent and adequate nutritional support.