Optimizing the cumulative cisplatin dose during radiotherapy in nasopharyngeal carcinoma: Dose-effect analysis for a large cohort

Objectives: Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). The cumulative cisplatin dose (CCD) during radiotherapy is an important prognostic factor; however, the optimal CCD is undetermined. Materials and methods: In this retrospective analysis, patients with locoregionally advanced NPC treated with single-agent cisplatin-based CCRT or RT alone from 2009 through 2015 were identified. CCD was entered into a multivariate Cox regression model as a continuous variable using natural cubic splines to allow for a nonlinear relationship between CCD and outcomes. The primary endpoint was overall survival, and the secondary endpoints were locoregional relapse-free survival and distant metastasis-free survival. Results: A total of 2 924 patients were included in our study, with a median CCD of 160 mg/m(2) (range, 0-300 mg/m(2)). As the CCD increased, the risk of death remained steady until 180 mg/m(2), then decreased sharply until 250 mg/m(2), and then increased until 300 mg/m(2). The optimal CCD of 230-270 mg/m(2) was associated with the lowest risk of death and disease relapse. However, the CCD had less prognostic value for disease control, especially for distant control among high-risk patients (N2-3 or T4). Conclusions: A CCD dose of 230-270 mg/m(2) (240 mg/m(2) is recommended) is optimal for patients with locoregionally advanced NPC, especially for those at low risk (T1-3 and N0-1). For high-risk patients (N2-3 or T4), additional chemotherapy should be administered before or after CCRT.