Body Composition As A Predictor Of Critical Toxicities In Patients With Locoregionally Nasopharyngeal Carcinoma Undergoing Neoadjuvant Chemotherapy

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Growing evidence has supported the use of neoadjuvant chemotherapy (NACT) prior to concurrent chemoradiation in locoregionally nasopharyngeal carcinoma (NPC). However, classical dosing of NACT agents based on body surface area (BSA) remains toxic in a considerable number of patients. Loss of skeletal muscle mass has been suggested in other malignancies to correlate with increased chemotherapy-induced toxicity, but its importance in NPC remains unclear. The aim of this study was to evaluate the impact of body composition on NACT-induced toxicities in patients with locoregionally NPC. A cohort of 96 NPC patients receiving NACT followed by concurrent chemoradiotherapy were analyzed. Based on pretreatment BSA, 78 patients were prescribed with TP regimen (docetaxel 75 mg/m2 d1+ cisplatin 25 mg/m2 d1-3) and 18 received GP (gemcitabine 1 g/m2 d1,8+ cisplatin 25 mg/m2 d1-3). Skeletal muscle index (SMI) (cm2/m2) and lean body mass (LBM) (kg) were measured through the cross-sectional images at the third lumbar vertebra on computerized tomography (CT). Dose of docetaxel and gemcitabine were normalized as dose/LBM (mg/kg). The ratio of male to female patients was 3:1 (72 vs. 24). Critical hematological toxicity (grade 3-4) was observed in 52 patients (54.2 %), majorly featured by neutrocytopenia for TP and thrombocytopenia for GP. Female patients (16/24) had more severe toxicity than male (36/72) (P = 0.059). Men had significantly higher mean SMI (53.4 vs. 41.1 cm2/m2, P<0.001) and LBM (mean: 52.6 vs. 37.1 kg, P<0.001). When normalized by LBM, women received remarkably higher dose of docetaxel (3.08 vs. 2.49 mg/kg, P<0.001) and gemcitabine (39.7 vs. 31.4 mg/kg, P = 0.006). Using a cut-off point of 50.2 cm2/m2, lower SMI was associated with higher incidence of severe chemotherapy toxicity (63.6% vs. 40.4%, P = 0.013). A stronger correlation was observed between LBM-adjusted dose and the incidence of chemotherapy toxicity. In TP regimen, with a cut-off value of 2.64 mg/kg, patients receiving higher docetaxel dose per LBM had much higher frequency of ≥grade 3 neutrocytopenia (67.6% vs. 36.6%, P = 0.003). Similar results were found in GP regimen, where gemcitabine dose/LBM over 31.86 mg/kg led to higher rate of ≥grade 3 thrombocytopenia (72.7% vs. 28.6%, P = 0.069). No correlation was found between chemotherapy and body mass index or BSA. High dose of docetaxel or gemcitabine/LBM seemed to forge no better objective response after NACT (complete/partial response rate: 80.0% vs. 72.2%, P = 0.439) than lower dose did. Low SMI and higher dose of docetaxel or gemcitabine per LBM were strongly related to severe toxicity after NACT in NPC patients, probably explaining the variation in toxicity among patients even with similar BSA and BMI. While BSA was insufficient in predicting toxicity, body composition showed good potential in guiding NACT dose for NPC patients. Future efforts are warranted to optimize the dosing strategy and further to improve prognosis.