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Sarcopenia is associated with reduced survival and increased vulnerability to toxicity in malignant diseases including squamous cell carcinoma of the head and neck (HNSCC). The prevalence of sarcopenia increases with age and is an important cause of functional decline in the elderly. We evaluated the influence of pre- and posttherapeutic sarcopenia in elderly (>65 years) HNSCC patients undergoing (chemo-)radiation regarding oncologic outcome and therapy-related toxicity.

280 elderly patients receiving radiotherapy or chemoradiation for HNSCC at the University of Freiburg Medical Center were included in this analysis. Pretherapeutic and posttherapeutic CT-scans of the head & neck region were available for 280 and 109 patients, respectively. Skeletal muscle area as an indicator for sarcopenia was outlined and quantified at the level of the third cervical vertebra (C3MA) in all CT scans. Using a previously published formula, C3MA was converted to the cross-sectional muscle area at the third lumbal vertebra (L3MA) and normalized for height (L3MI). After sex-specific standardization, pretherapeutic muscle indices were correlated with clinical parameters. After dichotomous categorization into “sarcopenic” and “non-sarcopenic” based on established cut-off values, the influence of pre- and posttherapeutic sarcopenia on overall-survival (OS), progression-free-survival (PFS) and treatment-related toxicity was calculated.

L3MA correlated significantly with pretherapeutic hemoglobin levels (p<0.01), pretherapeutic weight (p<0.01), and inversely with patient age (p<0.01). Patients classified as sarcopenic showed significantly larger tumors (T3/4 52.8% vs 69.0%, p<0.01) and a higher burden of comorbidity (CCI 4.8 vs 4.2, p=0.015) and experienced significantly higher chronic toxicities (CTCAE grade 3/4 24.0% vs 11.8%, p=0.022). OS and PFS were significantly deteriorated in sarcopenic patients with a median of 91 vs 23 month (p=0.002) and 47 vs 12 month (p<0.01), respectively. In the multivariate analysis taking into account patient performance status and smoking history, sarcopenia defined as low LM3A remained a significant prognostic factor deteriorating OS (HR 1.64, CI 1.07-2.52, p=0.023) . Upon completion of therapy, 33% of previously non-sarcopenic patients were classified as sarcopenic based on follow-up CT imaging. 97% of patients with pre-treatment sarcopenia remained sarcopenic. Median weight decreased by 5.6%, whereas median L3MA decreased by less than 1% over the course of therapy. Neither posttherapeutic sarcopenia nor the onset of sarcopenia during/after therapy significantly affected OS.

Pretherapeutic sarcopenia defined as a low skeletal muscle mass is a significant prognostic factor in elderly HNSCC patients undergoing (chemo-)radiation. Skeletal muscle indices seem to be independent prognosticators of therapy beyond patient weight loss and could allow for tailored supportive interventions to improve oncologic outcomes.