The impact of body composition parameters on severe toxicities in patients with locoregionally advanced nasopharyngeal carcinoma undergoing neoadjuvant chemotherapy

Background: Neoadjuvant chemotherapy (NACT) treatment in locoregionally advanced nasopharyngeal carcinoma ( LA-NPC) can lead to considerable toxicity. Loss of skeletal muscle mass showed relevance with increased chemotherapy-related toxicity and poor survival in various cancer types, but its significance in NPC remains unclear. This study aimed to investigate the relationship between body composition parameters and the incidence of NACT toxicity in LA-NPC patients. Methods: Ninety-six LA-NPC patients were retrospectively enrolled. All patients had pre-treatment abdominal computed tomography (CT) images to exclude distant metastasis. Lean body mass (LBM, kg) was estimated based on cross-sectional muscle area at the third lumbar vertebra (L3) level on CT, and skeletal muscle index (SMI, cm(2)/m(2)) was calculated. Doses of chemotherapeutics were normalized as dose/LBM (mg/kg). Grade 3-4 toxicity was defined as severe. The associations between body composition parameters and severe toxicities were assessed using univariate and multivariate logistic regression analyses. Optimal cutoff points were obtained with a receiver operating characteristic (ROC) curve. Results: Of the 96 patients, 81.2% received the docetaxel + cisplatin (TP) regimen, and the rest received the gemcitabine + cisplatin (GP) regimen. Males had more LBM and a higher SMI at baseline, and females received a markedly higher dose of docetaxel and gemcitabine per kg LBM (P<0.001). With a cutoff value of 52.7 cm(2)/m(2), patients with higher SMI showed lower risk of severe toxicity. For TP regimen group, those presented with grade 3-4 neutropenia had a higher dose per kg LBM. Univariate and multivariate analyses showed that the LBM-adjusted dose was significantly associated with severe neutropenia in the TP regimen group (P<0.001). The LBM-normalized docetaxel cutoff value of 2.64 mg/kg was a prominent predictor of = grade 3 neutropenia (P=0.003), but a higher dose of docetaxel per kg LBM did not provide a better objective response rate. Conclusions: LA-NPC patients with lower SMI and higher dose of docetaxel per kg LBM are more likely to suffer from severe treatment-related toxicity. Higher docetaxel dose per kg LBM is a prominent predictor for severe neutropenia, but not for NACT response. LBM showed good potential in toxicity risk prediction and dose determination.