Combining pretreatment plasma Epstein-Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: A cohort study

Abstract

This study aimed to evaluate the prognostic value of combining pretreatment Epstein-Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression-free survival (PFS). Kaplan-Meier curves with log-rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low-level EBV DNA group or non-CNN group had significantly better 5-year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129-3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005-2.214, P = .047), distant metastasis-free survival (DMFS) (HR = 1.661, 95% CI: 1.044-2.644, P = .032), but not locoregional relapse-free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of .324 (P < .001). Compared with low-level EBV DNA and non-CNN grouping, high-level EBV DNA and CNN grouping had poor PFS. The combined classification was an independent prognostic factor for OS (P < .001), PFS (P = .001), and DMFS (P = .018). Pretreatment plasma EBV DNA level and CNN status both closely correlated with prognosis of NPC patients in the IMRT era. Combined EBV DNA level and CNN status improves risk stratification and prognostic value.

Keywords: EBV; cervical node necrosis; cohort; nasopharyngeal carcinoma.

Figure 1

Lymph node status in four patient groups with nasopharyngeal carcinoma (NPC) by magnetic resonance images (MRI). (A) Axial T2‐weighted and (B) contrast‐enhanced T1‐weighted MRI in a 31‐y‐old man with pretreatment EBV DNA level of 6150 copies/mL and CNN; (C) Axial T2‐weighted and (D) contrast‐enhanced T1‐weighted MRI in a 42‐y‐old man with pretreatment EBV DNA level of 67 700 copies/mL and non‐CNN; (E) Axial T2‐weighted and (F) contrast‐enhanced T1‐weighted MRI in a 50‐y‐old woman with pretreatment EBV DNA level of 1460 copies/mL and CNN; (G) Axial T2‐weighted and (H) contrast‐enhanced T1‐weighted MRI in a 31‐y‐old man with pretreatment EBV DNA level of 1120 copies/mL and non‐CNN

Figure 2

The percentage of CNN status(left) and EBV DNA level(right) in different clinical stages. *II, clinical stage II; III, clinical stage III; IV, clinical stage IV; *non‐CNN, non cervical node necrosis; CNN, cervical node necrosis

Figure 3

Kaplan‐Meier curves of overall (A), Progression‐free (B), Locoregional relapse‐free (C), and Distant metastasis‐free (D) survival outcomes for the 607 NPC patients stratified by EBV DNA level

Figure 4

Kaplan‐Meier curves of overall (A), Progression‐free (B), Locoregional relapse‐free (C), and Distant metastasis free (D) survival outcomes for the 607 NPC patients stratified by CNN status

Figure 5

Kaplan‐Meier curves of overall (A), Progression‐free (B), Locoregional relapse‐free (C) and Distant metastasis‐free (D) survival outcomes for the 607 NPC patients stratified by EBV DNA level and CNN. *LLE and non‐CNN, low‐level EBV DNA and non‐CNN; LLE and CNN, low‐level EBV DNA and CNN; HLE and non‐CNN, high‐level EBV DNA and non‐CNN; HLE and CNN, high‐level EBV DNA and CNN