Sarcopenia as a Prognostic Marker in Elderly Head and Neck Squamous Cell Carcinoma Patients Undergoing (Chemo-)Radiation

SIMPLE SUMMARY: Sarcopenia, i.e., the loss of muscle mass is a risk factor for reduced survival and increased treatment-associated toxicities in many cancers, and it increases with age. In this analysis, we investigated sarcopenia and sarcopenia dynamics during treatment in elderly patients (>65 yrs) with head-and-neck cancers undergoing (chemo)radiotherapy. Patients who exhibited sarcopenia prior to radiotherapy had a significantly reduced overall survival as well as an increased risk for incurring higher-grade toxicities. Additionally, pre-treatment sarcopenia in elderly patients correlated with a decreased body weight, a higher level of comorbidities, larger tumor size and increasing age. During (chemo)radiotherapy, muscle mass in patients remained relatively stable, and post-therapeutic sarcopenia did no longer correlate with patient survival. Considering the vulnerability of elderly patients with head-and-neck cancers, assessing sarcopenia prior to radiotherapy may help in shared decision-making regarding the optimal treatment. Additionally, sarcopenia can be a valuable predictive marker regarding the necessity of early supportive measures in elderly patients with head-and-neck cancers undergoing radiotherapy. ABSTRACT: Sarcopenia is associated with reduced survival and increased toxicity in malignant diseases. The prevalence of sarcopenia increases with age and is an important cause of functional decline. We analyzed sarcopenia and sarcopenia dynamics in elderly head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiation. Skeletal muscle mass of 280 elderly HNSCC-patients (>65 yrs) receiving curative (chemo)radiation was manually outlined and quantified on CT scans at the level of the C3 (C3MA). Cross-sectional muscle area at L3 (L3MA) was calculated and normalized to height (L3MI). Frequency distributions of clinical parameters as well as overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were calculated regarding sarcopenia. Calculated L3MA correlated with pretherapeutic hemoglobin-levels (ρ = 0.280) bodyweight (ρ = 0.702) and inversely with patient-age (ρ = −0.290). Sarcopenic patients featured larger tumors (T3/4 69.0% vs. 52.8%, p < 0.001), a higher burden of comorbidity (age-adjusted Charlson Comorbidity Index 4.8 vs. 4.2, p = 0.015) and more severe chronic toxicities (CTCAE grade 3/4 24.0% vs. 11.8%, p = 0.022). OS was significantly deteriorated in sarcopenic patients with a median of 23 vs. 91 months (logrank p = 0.002) (HR 1.79, CI 1.22–2.60, p = 0.003) and sarcopenia remained an independent prognostic factor for reduced OS in the multivariate analysis (HR 1.64, CI 1.07–2.52, p = 0.023). After therapy, 33% of previously non-sarcopenic patients developed sarcopenia, while 97% of pre-treatment sarcopenic remained sarcopenic. Median bodyweight decreased by 6.8%, whereas median calculated L3MA decreased by 2.4%. In contrast to pretherapeutic, post-therapeutic sarcopenia is no prognosticator for reduced OS. Pretherapeutic sarcopenia is a significant prognostic factor in elderly HNSCC patients undergoing (chemo-)radiation and should be considered in pretherapeutic decision-making. Its role as a predictive marker for tailored supportive interventions merits further prospective evaluation.