Exploring the Optimal Chemotherapy Strategy for Locoregionally Advanced Children and Adolescent Nasopharyngeal Carcinoma Based on Pretreatment Epstein-Barr Virus DNA Level in the Era of Intensity Modulated Radiotherapy

The present study aimed to explore the optimal chemotherapy strategy for locoregionally advanced children and adolescent nasopharyngeal carcinoma (LcaNPC), based on the level of pretreatment plasma Epstein-Barr virus DNA (pEBV-DNA) in the era of intensity modulated radiation therapy (IMRT).This real-world, retrospective study consecutively reviewed locoregionally advanced nasopharyngeal carcinoma patients younger than 22 years old from 2006 to 2016 in the Sun Yat-sen University Cancer Center. The Kaplan-Meier method with the log-rank test and the Cox regression model were used to investigate the survival outcomes of different chemotherapy intensities and pEBV-DNA. Treatment-related toxicity was also evaluated using the chi-squared test or Fisher's exact test.A total of 179 patients were enrolled, including 86 patients in the high-risk group (pEBV-DNA ≥7,500 copies/ml) and 93 patients in the low-risk group (pEBV-DNA <7,500 copies/ml). Among all patients, those receiving low intensity induction chemotherapy (IC courses = 2) had a better 5-year overall survival (OS) than those receiving no IC (P = 0.025) and high intensity IC (IC courses >2) (P = 0.044). In the high-risk group, receipt of low intensity IC showed significant 5-year OS (P = 0.032), progression-free survival (PFS) (P = 0.027), and 5-year distant metastasis-free survival (DMFS) (P = 0.008) benefits compared with not receiving IC. Multivariate analyses identified that not receiving IC was a risk factor compared with low intensity IC for OS (hazard ratio (HR) = 10.933, P = 0.038) among all patients. Moreover, in the high-risk group, not receiving IC was a risk factor for 5-year OS (HR = 10.878, P = 0.038), 5-year PFS (HR = 5.705, P = 0.041), and 5-year DMFS (HR = 10.290, P = 0.040) compared to low intensity IC. There were no differences in survival for patients treated with or without concurrent chemotherapy.Two courses of platinum-based IC might be the optimal induction chemotherapy intensity to reduce risk of death, progression, and distant metastasis in patients with high pEBV-DNA levels.