Negative Epstein-Barr Virus DNA Research Articles

Histogram analysis of quantitative parameters from synthetic MRI: correlations with prognostic factors in nasopharyngeal carcinoma.

To evaluate the correlation between histogram parameters derived from synthetic magnetic resonance imaging (SyMRI) and prognostically relevant factors in nasopharyngeal carcinoma (NPC). Fifty-nine consecutive NPC patients were prospectively enrolled. Quantitative parameters (T1, T2, and proton density (PD)) were obtained by outlining the three-dimensional volume of interest (VOI) of all lesions. Then, histogram analysis of these quantitative parameters was performed and the correlations with prognostically relevant factors were assessed. By choosing appropriate cutoff, we divided the sample into two groups. Independent-samples t test/Mann-Whitney U test was used and ROC curve analysis was further processed. Histogram parameters of the T1, T2, and PD maps were positively correlated with the Ki-67 expression levels, and PD_mean was the most representative parameter (AUC: 0.861). The PD map exhibited good performance in differentiating epidermal growth factor receptor (EGFR) expression levels (AUC: 0.706~0.732) and histological type (AUC: 0.650~0.660). T2_minimum was highest correlated with Epstein-Barr virus (EBV) DNA levels (r = - 0.419), and PD_75th percentile exhibited the highest performance in distinguishing positive and negative EBV DNA groups (AUC: 0.721). T1_minimum was statistically correlated with EA-IgA expression (r = - 0.313). Additionally, several histogram parameters were negatively correlated with tumor stage (T stage: r = - 0.259 ~ - 0.301; N stage: r = - 0.348 ~ - 0.456; clinical stage: r = - 0.419). Histogram parameters of SyMRI could reflect tissue intrinsic characteristics and showed potential value in assessing the Ki-67 and EGFR expression levels, histological type, EBV DNA level, EA-IgA, and tumor stage. • SyMRI combined with histogram analysis may help clinicians to assess different prognostic factor statuses in nasopharyngeal carcinoma. • The PD map exhibited good discriminating performance in the Ki-67 and EGFR expression levels. • Histogram parameters of SyMRI were negatively correlated with EBV-related blood biomarkers and TNM stage.

Radiotherapy Alone Versus Concurrent or Adjuvant Chemoradiotherapy for Nasopharyngeal Carcinoma Patients with Negative Epstein–Barr Virus DNA after Induction Chemotherapy

The purpose of this study was to compare the efficacy and toxicity of induction chemotherapy (IC) plus radiotherapy (RT) and IC plus concurrent or adjuvant chemoradiotherapy (CCRT/AC) in nasopharyngeal carcinoma (NPC) patients with negative Epstein-Barr virus DNA (EBV DNA) after IC. A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC + RT group and the IC + CCRT/AC group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan-Meier method. Propensity score matching (PSM) was performed to balance the variables. The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC + RT and the IC + CCRT/AC groups, both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that the treatment schedule was not an independent predictor for survival rates. Patients in the IC + RT group had fewer treatment-related acute toxicities and better tolerance. IC + RT displayed similar survival outcomes as IC + CCRT/AC for NPC patients with negative post-IC EBV DNA.

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA

BackgroundInflammatory parameters and Epstein–Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA.MethodsA total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan–Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher’s exact test.ResultsThe optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters.ConclusionsThe SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein-Barr virus DNA.

To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004). NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.

Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

BackgroundCirculating cell-free Epstein–Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons.MethodsWe analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI).ResultsA total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.ConclusionsAnalysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399.)

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

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.

Quantification of circulating Epstein–Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance

Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its significance in natural killer/T-cell lymphoma treated with the novel regimen SMILE was investigated. EBV DNA was quantified with a World Health Organization EBV standard in 910 plasma samples collected during 230 courses of SMILE in 56 patients. Median presentation EBV DNA was 1900 (0-1.4 × 10(7)) IU/ml. Presentation EBV DNA was significantly associated with tumor load and treatment response. To examine lymphoma chemosensitivity, EBV DNA changes after SMILE were evaluated. EBV DNA after SMILE (I) significantly correlated with tumor load and treatment response. Two dynamic parameters were further analyzed: negative EBV DNA after SMILE (I) and EBV DNA change patterns during treatment (A: persistently undetectable; B: persistently detectable<presentation; C: persistently detectable>presentation). Negative EBV DNA after SMILE (I) and pattern A EBV DNA change significantly correlated with lower tumor load and superior outcome. Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBV DNA after SMILE (I) had the most significant impact (P<0.001) on overall survival and pattern A EBV DNA change had the most significant impact (P=0.002) on disease-free survival. Presentation EBV DNA, IPI and Korean prognostic scores were not independent prognostic factors.

Early detection of nasopharyngeal carcinoma by plasma Epstein‐Barr virus DNA analysis in a surveillance program

Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

Prognostic Significance of Circulating Epstein-Barr Virus (EBV) DNA in Non-Hodgkin's Lymphoma.

Abstract 1936Poster Board I-959 Introduction:Epstein-Barr virus (EBV) is well-known as an etiologic agent of lymphoproliferative disorders. Almost all types of sporadic non-Hodgkin's lymphoma (NHL) of both B-cell and T-cell origins have been demonstrated to have EBV-infected tumor cells. However, the prognostic significance of EBV viral load has not been established yet. Methods: To monitor quantitative EBV DNA load, real time quantitative PCR of EBV BZLF1 DNA was done using RealArt® EBV LC PCR reagents (Artus) from whole blood samples drawn from newly diagnosed NHL patients at the time of diagnosis and during the follow-up. Results: Between July 2006 and March 2009, a total of 233 patients (including 120 [51.5%] diffuse large B-cell lymphoma [DLBCL]; 18 [7.7%] natural killer (NK)/T-cell lymphoma; and 11 [4.7%] peripheral T-cell lymphoma, unspecified) were reviewed and analyzed. Among them, 33 (14%) patients, had a detectable EBV DNA (positive group) while 200 (85%) patients did not (negative group). Those in positive group had a more advanced disease and a higher LDH level than those in negative group (P=0.003 and 0.007, respectively). With a median follow up of 11.3 months (range 1.2-34.9), 14 (42.4%) of the 33 patients in positive group had a progressive or relapsed disease while 30 (15%) of the 200 patients in negative group did (P<0.001). One-year overall survival (OS) rate was 72.5% in positive group while that was 82.9% in negative group (log-rank P=0.001). Interestingly, conversion to negative EBV DNA during the follow-up was associated with a lower probability of progressive or relapsed disease (P=0.004). NK/T-cell lymphoma patients having an EBV DNA survived shorter than those having not. However, in DLBCL patients, there was no difference in survival between those having an EBV DNA and those not. Conclusions: The presence of EBV DNA at diagnosis and the negative conversion of EBV DNA during the follow-up might have prognostic significance in patients with NHL. Disclosures:No relevant conflicts of interest to declare.