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

// Salvatore Alfieri 1 , Nicola Alessandro Iacovelli 2 , Sara Marceglia 3 , Irene Lasorsa 3 , Carlo Resteghini 1 , Francesca Taverna 4 , Arabella Mazzocchi 4 , Ester Orlandi 2 , Marco Guzzo 5 , Roberto Bianchi 5 , Diana Fanti 6 , Laura Pala 7 , Sara Racca 8 , Roee Dvir 8 , Pasquale Quattrone 9 , Annunziata Gloghini 9 , Chiara Costanza Volpi 9 , Roberta Granata 1 , Cristiana Bergamini 1 , Laura Locati 1 , Lisa Licitra 1, 10 and Paolo Bossi 1 1 Department of Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 2 Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3 Department of Engineering and Architecture, University of Trieste, Trieste, Italy 4 Laboratory of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 5 Department of Head and Neck Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 6 Laboratory of Clinical Chemistry and Microbiology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy 7 Department of Medical Oncology of Melanoma and Sarcoma, Istituto Europeo di Oncologia, Milan, Italy 8 Laboratory of Clinical Microbiology & Virology, San Raffaele IRCCS Hospital, Milan, Italy 9 Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 10 Department of Medical Oncology 3, University of Milan, Milan, Italy Correspondence to: Salvatore Alfieri, email: salvatore.alfieri@istitutotumori.mi.it Keywords: nasopharyngeal cancer, Epstein-Barr virus, prognosis, head and neck cancer, non endemic Received: February 06, 2017 Accepted: April 12, 2017 Published: May 11, 2017 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.