Prevalence and significance of plasma Epstein-Barr Virus DNA level in nasopharyngeal carcinoma

Abstract

Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I-IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P < 0.001). Our study demonstrated the clinical significance of the plasma EBV DNA level at specific time points, as well as of the dynamic changes in the EBV DNA level. Disappearance of plasma EBV DNA after treatment was associated with better survival.

Keywords: EBV DNA; IMRT; dynamic change; intensity-modulated radiotherapy; nasopharyngeal carcinoma; predictor.

Fig. 1.

Progression-free survival (A) and overall survival (B) according to pre-treatment plasma EBV DNA level and progression-free survival (C) and overall survival (D) according to staging and pre-treatment plasma EBV DNA level. PFS = progression-free survival; OS = overall survival, U = undetectable, D = detectable.

Fig. 2.

Dynamic changes in plasma EBV DNA level in 204 nasopharyngeal carcinoma patients.

Fig. 3.

PFS (A) and OS (B) according to plasma EBV DNA level post-treatment, and PFS (C) and OS (D) according to dynamic change in plasma EBV DNA level post-treatment. PFS = progression-free survival; OS = overall survival, U = undetectable, D = detectable; U_pre = EBV DNA undetectable pre-treatment, U_post = EBV DNA undetectable post-treatment, D_pre = EBV DNA undetectable pre-treatment, D_post = EBV DNA undetectable post-treatment.