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

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.

Impact of age on survival of locoregional nasopharyngeal carcinoma: An analysis of the Surveillance, Epidemiology, and End Results program database, 2004‐2013

“…EBV infection also contributes to pathogenesis of NPC via the Epstein‐Barr nuclear antigen 1 ( EBNA1 ), latent membrane protein 1 ( LMP1 ), LMP2 , and BamH1‐A fragment rightward reading frame 1 ( BARF1 ) genes (reviewed in Tsang et al, 2015 and Zhang et al, 2017). A growing body of evidence supports the hypothesis that activity of these and other genes in EBV‐positive patients with NPC results in substantially poorer outcomes in endemic as well as non‐endemic countries . Future studies of other cancer registries and databases in the US should be used to examine the relationship between HPV infection status, age, and race in more detail.…”

Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

“…A higher concentration was associated with a higher mortality, poorer PFS and poorer DMFS. 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 23 Leung et al . 5 retrospectively reviewed 376 NPC patients who were treated with conventional RT.…”

“… 3 Others confirmed the prognostic value of pre-EBV in predicting clinical outcomes despite the different pre-EBV cut-off values. 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 The persistent post-treatment EBV DNA concentration (post-EBV) has the strongest risk of disease relapse and distant metastasis 4 , 7 , 12 , 13 , 14 and may help in treatment modification, such as the intensification of adjuvant chemotherapy regimens. 15 …”

Baseline MRI-Radiomics Can Predict Overall Survival in Non-Endemic EBV-Related Nasopharyngeal Carcinoma Patients

“…EBER status assessment and quantification techniques for EBV-DNA positivity were defined according to our previous work [ 15 ].…”

“…However, whether radiomics signatures could assist in predicting outcome in non-endemic areas and/or it could be a potential tool for increasing the precision of TNM criteria in addition to well-known prognostic biomarkers and baseline Epstein-Barr virus-DNA (EBV-DNA) load has been poorly studied [ 15 ].…”