The effect of skeletal muscle mass on dose-limiting toxicities during (chemo)radiotherapy in patients with head and neck cancer: A systematic review and meta-analysis.

Radiotherapy (RT) is a standard treatment for head and neck cancer (HNC) and chemoradiotherapy (CRT) is indicated for patients with locally advanced disease. Toxicities during treatment are common and can lead to early cessation of chemotherapy and radiotherapy (RT) interruptions, which can affect oncologic outcomes. Skeletal muscle mass (SMM) is a new biomarker to predict toxicities and overall survival. The aim of this systematic review is to provide an overview of studies towards the associations between SMM and dose limiting toxicity (DLT) and/or RT interruptions in HNC patients. A systematic literature search was conducted and yielded 270 studies. Inclusion criteria were articles published in English that investigated the effect of low SMM measured in humans with HNC on toxicities during CRT or RT. Studies that did not investigate oral cavity, oropharynx, larynx, hypopharynx, nasopharynx cancers or carcinoma of unknown primary were excluded. This led to the inclusion of 22 original studies. The prevalence of low SMM ranged from 19.7 % to 74.7 %. SMM was often assessed by measuring the cross-sectional muscle area at the level of the third cervical vertebra on computed tomography scans. Cut-off values used to categorize patients in SMM groups varied. In the meta-analyses heterogeneity was moderate (I = 68 % and 50 % respectively). Patients with low SMM had higher, but only borderline significant, odds of DLT during CRT (OR 1.60; 95 % CI 1.00-2.58; p = 0.0512) and RT interruptions (OR 1.89; 95 % CI 1.00-3.57; p = 0.0510) compared to patients without low SMM. To conclude, in HNC patients low SMM, defined with different methods and cut-off values, is associated with DLT and RT interruptions during (C)RT, although the difference is only borderline statistically significant.