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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)47780-47789
Number of pages10
JournalOncotarget
Volume8
Issue number29
DOIs
Publication statusPublished - Jul 18 2017

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Nasopharyngeal Neoplasms
Human Herpesvirus 4
DNA
Viral Load
Therapeutics
Disease-Free Survival
Induction Chemotherapy
Linear Models
Multivariate Analysis
RNA
Survival
Survival Analysis
Statistical Factor Analysis

Keywords

  • Journal Article

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Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area. / Alfieri, Salvatore; Iacovelli, Nicola Alessandro; Marceglia, Sara; Lasorsa, Irene; Resteghini, Carlo; Taverna, Francesca; Mazzocchi, Arabella; Orlandi, Ester; Guzzo, Marco; Bianchi, Roberto; Fanti, Diana; Pala, Laura; Racca, Sara; Dvir, Roee; Quattrone, Pasquale; Gloghini, Annunziata; Volpi, Chiara Costanza; Granata, Roberta; Bergamini, Cristiana; Locati, Laura; Licitra, Lisa; Bossi, Paolo.

In: Oncotarget, Vol. 8, No. 29, 18.07.2017, p. 47780-47789.

Research output: Contribution to journalArticle

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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.",
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T1 - Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area

AU - Alfieri, Salvatore

AU - Iacovelli, Nicola Alessandro

AU - Marceglia, Sara

AU - Lasorsa, Irene

AU - Resteghini, Carlo

AU - Taverna, Francesca

AU - Mazzocchi, Arabella

AU - Orlandi, Ester

AU - Guzzo, Marco

AU - Bianchi, Roberto

AU - Fanti, Diana

AU - Pala, Laura

AU - Racca, Sara

AU - Dvir, Roee

AU - Quattrone, Pasquale

AU - Gloghini, Annunziata

AU - Volpi, Chiara Costanza

AU - Granata, Roberta

AU - Bergamini, Cristiana

AU - Locati, Laura

AU - Licitra, Lisa

AU - Bossi, Paolo

PY - 2017/7/18

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N2 - 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.

AB - 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.

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