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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.