Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma

Abstract

Epstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups. Patients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077-3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392-3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072-2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987-3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis. Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.