Relationship of Sarcopenia to Tolerance of Chemotherapy During Definitive Treatment of Primary Anal Squamous Cell Carcinoma

Abstract

Primary therapy for anal squamous cell carcinoma consists of definitive radiation with concurrent chemotherapy, most commonly 5-fluorouracil and mitomycin-C. This regimen is associated with significant cutaneous, hematologic, and gastrointestinal toxicity. Sarcopenia, or low skeletal muscle mass, has been described as an adverse prognostic factor and predictor of poor tolerance to therapy across a range of malignancies, including breast, gynecologic and head and neck cancers. Here, we sought to determine if the presence of sarcopenia at the initiation of therapy is associated with increased rates of toxicity and poorer tolerance of definitive treatment for primary anal squamous cell carcinoma. This was a review of patients treated with curative intent for anal squamous cell carcinoma at a single academic medical center between 2007 and 2017, median follow up was 38 months. Analysis was limited to patients receiving definitive radiation with concurrent chemotherapy. Sarcopenia was objectively defined, using previously validated methods, as a skeletal muscle index (SMI) <41 cm2/m2 for female patients regardless of body mass index (BMI); for male patients sarcopenia was defined as SMI<43cm2/m2 for BMI<25 and <53 cm2/m2 for BMI >25. SMI calculations were performed using the average skeletal muscle cross sectional areas of two sequential axial CT slices at the L3 vertebral level obtained from radiation planning computed tomography scans. The image analysis was performed by a single trained observer using Sliceomatic software with a Hounsfield unit threshold of -29 to 150 to define skeletal muscle. Sarcopenia as a predictor for treatment toxicity was analyzed using Chi-Square testing. Overall survival and progression free survival were compared with 2-sample t tests. Sixty-one patients were included in the analysis with 49% meeting criteria for sarcopenia. Stage did not differ although sarcopenic patients were significantly more elderly than those without sarcopenia (mean 72 vs 58 years, p<0.001). Patients with sarcopenia were significantly more likely to have chemotherapy breaks, chemotherapy dose reductions, and incomplete chemotherapy courses compared to non-sarcopenic patients (33.3% vs 9.7%; p = 0.02). Sarcopenia was not predictive of more radiation treatment breaks, hematologic toxicity, progression free survival or overall survival. Sarcopenia is predictive of reduced tolerance to chemotherapy among patients receiving definitive combined modality therapy for primary anal carcinoma. We found no association between sarcopenia and tolerance of radiation therapy or survival outcomes.