Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era

Abstract

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000 copies/mL, patients with an EBV DNA ≥ 4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

FIGURE 1

Log (EBV DNA) are expressed as the median and 5% to 95% percentile in patients (A) with/without progression, (B) with/without distant metastasis, and (C) survivor or deaths. P value was calculated by Wilcoxon rank-sum test.EBV DNA = Epstein–Barr Virus DNA, MF = median follow-up time.

FIGURE 2

Kaplan–Meier curves of progression-free survival, distant metastasis-free survival, and overall survival according to the pretreatment EBV DNA levels (<4000 copies/mL vs ≥4000 copies/mL) for local and regionally advanced NPC patients: disease-free survival (A), distant metastasis-free survival (B), and overall survival (OS).EBV DNA = Epstein–Barr Virus DNA, NPC = nasopharyngeal carcinoma, OS = overall survival.

FIGURE 3

Kaplan–Meier curves of progression-free survival and distant metastasis-free survival according to the pretreatment EBV DNA levels (<4000 copies/mL vs ≥4000 copies/mL) for subgroup analysis. Progression-free survival (A), distant metastasis-free survival (B), and overall survival (C) for patients staged III; progression-free survival (D), distant metastasis-free survival (E), and overall survival (F) for patients staged IVa-b. EBV DNA = Epstein–Barr Virus DNA.