Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area.

Salvatore Alfieri,Roee Dvir,Annunziata Gloghini,Roberta Granata,Arabella Mazzocchi,Chiara Costanza Volpi,Pasquale Quattrone,Diana Fanti,Irene Lasorsa,Sara Racca,Carlo Resteghini,Sara Marceglia,Nicola Alessandro Iacovelli,Francesca Taverna,Roberto Bianchi,Marco Guzzo,Laura Pala,Paolo Bossi,Ester Orlandi,Lisa Licitra,Cristiana Bergamini,Laura D Locati

doi:10.18632/oncotarget.17822

Abstract

The prognostic value of pre-treatment Epstein-Barr Virus (EBV) DNA viral load for non-endemic, locally-advanced, EBV-related nasopharyngeal cancer (NPC) patients is yet to be defined. All patients with EBV encoded RNA (EBER)-positive NPC treated at our Institution from 2005 to 2014 with chemotherapy (CT) concurrent with radiation (RT) +/- induction chemotherapy (ICT) were retrospectively reviewed. Pre-treatment baseline plasma EBV DNA (b-EBV DNA) viral load was detected and quantified by PCR. Median b-EBV DNA value was correlated to potential influencing factors by univariate analysis. Significant variables were then extrapolated and included in a multivariate linear regression model. The same variables, including b-EBV DNA, were correlated with Disease Free Survival (DFS) and Overall Survival (OS) by univariate and multivariate analysis.A total of 130 locally-advanced EBER positive NPC patients were evaluated. Overall, b-EBV DNA was detected in 103 patients (79.2%). Median viral load was 554 copies/mL (range 50–151075), and was positively correlated with T stage (p=0.002), N3a-b vs N0-1-2 stage (p=0.048), type of treatment (ICT followed by CTRT, p=0.006) and locoregional and/or distant disease recurrence (p=0.034). In the overall population, DFS and OS were significantly longer in patients with pre-treatment negative EBV DNA than in positive subjects at the multivariate analysis.Negative b-EBV DNA can be considered as prognostic biomarker of longer DFS and OS in NPC in non-endemic areas. This finding needs confirmation in larger prospective series, with standardized and inter-laboratory harmonized method of plasma EBV DNA quantification.

Highlights

Nasopharyngeal cancer (NPC), commonly affecting Asian countries, is a very rare disease in Caucasian countries (0.5 new cases/year per 100.000 persons/year) [1, 2]
This study evaluates the prognostic role of baseline Epstein-Barr Virus (EBV) DNA viral load for locally-advanced EBV-related nasopharyngeal cancer (NPC) patients in a non-endemic area
The results were the same (Table 3) and the relationship between b-EBV DNA and Disease Free Survival (DFS) and Overall Survival (OS) remained significant (P

Summary

Introduction

Nasopharyngeal cancer (NPC), commonly affecting Asian countries (incidence rate as high as 20-50 per 100.000 persons/year), is a very rare disease in Caucasian countries (0.5 new cases/year per 100.000 persons/year) [1, 2]. Epstein-Barr Virus (EBV) is one of the most important causative factors of NPC It has a heterogeneous diffusion, which might account, at least in part, for the different incidence between Southern China or Southeast Asia (endemic area) and Europe or USA (non-endemic area). In the non-endemic area, only two limited case series (34 and 36 patients, respectively) investigating the role of EBV DNA have been reported [7, 8]. These studies showed a direct relationship between pre-treatment EBV DNA viral load and baseline clinical tumor stage, and between EBV DNA increase and tumor recurrence during follow-up. Ferrari et al [8] tried to demonstrate a prognostic significance of pre-treatment EBV DNA by reporting a significant correlation between higher baseline EBV DNA values and shorter DiseaseFree Survival (DFS) at univariate analysis (not confirmed after adjusting for age)

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Conclusion