Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with RT

Purpose/Objective Sarcopenia, defined as the loss of skeletal muscle mass and strength, is emerging as an adverse prognostic factor for both survival and complication risk in cancer patients. The aim of this study was to determine the impact of sarcopenia on several survival parameters and late toxicity in a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) treated with primary radiotherapy (RT). Material/methods Patients with HNSCC who were treated with definitive RT with or without systemic treatment from January 2007 to June 2016 were included. Prospectively collected variables were retrospectively analysed. The planning CT-scan was used to measure the cross-sectional area (CSA) of skeletal muscles at the level of the third cervical vertebra (C3). The prediction rule by Swartz et al. was used to estimate CSA at the third lumbar vertebra (L3). L3 skeletal muscle index (SMI) was calculated. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was investigated using univariate (Kaplan Meier) and multivariate (Cox proportional hazards regression) analysis. To analyse the association of sarcopenia with physician-rated grade ≥2 toxicity (i.e. xerostomia and dysphagia) and with moderate-to-severe patient-rated xerostomia, multivariable logistic regression analyses were performed to create association models. Results The study population was composed of 750 patients with HNSCC. The cut-off value of sarcopenia was set at SMI <42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding with the lowest gender specific quartile. Patients with sarcopenia had significantly poorer survival rates than others. The 3-year OS in sarcopenic patients was 53% compared to 73% in non-sarcopenic patients (p<0.001) and the 3-year DFS was resp. 59% and 76% (p<0.001). However, sarcopenia was only significantly associated with OS and DFS in patients with WHO performance score (WHO-score)>0 (resp. p<0.001 and p=0.003) and in those with locally advanced disease (stage III-IV) (both p<0.001) (Figure 1 OS stratified by stage of disease). The multivariate analysis showed that sarcopenia was an independent adverse prognostic factor for OS (p=0.004), next to age, WHO-score, tumour stage and primary tumour site and for DFS (p=0.013), next to age, WHO-score and tumour stage (Table 1). In the univariate analysis, sarcopenia was associated with more radiation-induced xerostomia and dysphagia at six and twelve months after treatment, but no such association was found in multivariate analysis after correcting for confounders. Conclusion In this prospective cohort study, sarcopenia was significantly associated with poorer OS and DFS, for patients with lower performance (WHO-score >0) and locally advanced disease (stage III-IV), with similar prognostic value as WHO-score, tumour stage and primary tumour site. Given that the SMI can be easily assessed on planning-CT scan, clinical introduction is easy and adds important and clinically relevant information to assess patient outcome.