Pre-treatment Plasma Epstein-Barr Virus DNA Levels Research Articles

Value of dynamic contrast-enhanced magnetic resonance imaging for determining the plasma Epstein-Barr virus status and staging of nasopharyngeal carcinoma

AimTo determine the associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters and plasma Epstein-Barr virus (EBV) DNA status and nasopharyngeal carcinoma (NPC) stages. MethodsWe prospectively studied the DCE-MRI results of 47 patients with newly diagnosed NPC and their pre-treatment plasma EBV DNA levels. We recruited all patients who had undergone MRI (1.5 T) simulation at the radiation therapy department of our institute between January 2018–2019. Regions of interest were drawn at primary tumors, and DCE-MRI parameters, including mean values of Ktrans, Kep, Ve, and Vp, were recorded. Spearman's rank correlation was used to identify significant associations between the DCE-MRI parameters and the plasma EBV DNA level and NPC stages. Mann-Whitney U tests and unpaired t-test were performed to compare the DCE-MRI parameters among different groups and to identify optimal cut-off values using receiver operating characteristic curves. ResultsWe found that the DCE-MRI parameters correlated with the plasma EBV DNA levels and NPC stages. Positive plasma EBV DNA was correlated with lower Kep (optimal cut-off value, 2.1 min−1; area under the curve [AUC], 0.714) and higher Ve (optimal cut-off value, 0.675; AUC, 0.706). Ve higher than 0.765 (AUC, 0.678) was correlated with plasma EBV DNA (≥2300 copies mL−1). Higher Ktrans (cut-off value, 1.495 min−1) was correlated with high-T stage (AUC, 0.767) and high-stage group (AUC, 0.711). ConclusionsThe DCE-MRI parameters are correlated with the plasma EBV DNA status and NPC stages. Therefore, DCE-MRI findings may be used as imaging biomarkers for patients with NPC.

Prognostic value of plasma Epstein\u2013Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

BackgroundThe value of Epstein–Barr virus (EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma (NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment follow-up in the patients with NPC who have undergone intensity-modulated radiotherapy.MethodsThe medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within 3 months after treatment, and then every 3–12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.ResultsOf the 385 patients, 267 (69.4%) had detectable pretreatment plasma EBV DNA (> 0 copy/mL) and 93 (24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months (range 9.3–73.8 months). Detectable EBV DNA during posttreatment follow-up was found in 14.4% (17/118) and 28.5% (76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8% (40/313) of patients who remained disease-free, 56.4% (22/39) of patients with locoregional recurrence alone, and 93.9% (31/33) of patients with distant metastasis as the first recurrence event (P < 0.001); 6.5% (19/292) of patients with undetectable EBV DNA and 57.0% (53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve (AUC) value (0.804, 95% confidence interval 0.741–0.868) for predicting tumor recurrence (sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).ConclusionPlasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status.

PurposeThe main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV).ResultsOf the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC.Methods and MaterialsData on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared.ConclusionsEBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients.

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma.

The level of Epstein-Barr virus DNA (EBV-DNA) in the plasma prior and subsequent to treatment is a reliable biomarker for the screening, diagnosis, monitoring and prognosis of nasopharyngeal carcinoma (NPC). The present retrospective study aimed to determine whether pre- and post-treatment levels of plasma EBV-DNA were predictive of survival in a large sample of patients with NPC. The level of plasma EBV-DNA in 637 NPC patients prior and subsequent to treatment was determined by quantitative polymerase chain reaction. The value of pre- and post-treatment plasma EBV-DNA in predicting the survival of NPC patients was then analyzed. The results revealed that pre-treatment plasma EBV-DNA loads were significantly higher in patients with NPC than those in healthy controls (P<0.001). The percentage of patients with positive plasma EBV-DNA was markedly higher prior to treatment (70.64%; median, 1150 copies/ml; range, 0-9.75×106 copies/ml) than following treatment (25.99%; median, 0 copies/ml; range, 0-3.83×106 copies/ml) (P<0.001). Patients with a high plasma EBV-DNA load presented with a higher clinical tumor classification, lymph node status, metastatic status and overall cancer stage. The risk of NPC relapse and mortality was higher in patients with pre-treatment plasma EBV-DNA levels of ≥1,500 copies/ml than that in patients with <1,500 copies/ml. Furthermore, the risk of relapse and mortality was higher in patients with positive post-treatment plasma EBV-DNA than in patients with negative post-treatment plasma EBV-DNA. Detectable post-treatment plasma EBV-DNA was the most significant prognostic factor to affect relapse-free survival, whilst metastasis was the prognostic factor with the greatest effect on overall survival. These data indicated that pre- and post-treatment levels of plasma EBV-DNA were able to predict the prognosis of NPC. This finding may provide novel references for research and clinical practice.

Clinical significance of plasma Epstein–Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma (NPC) is an Epstein–Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia. ObjectivesTo evaluate the clinical values of pre-treatment plasma EBV DNA levels in Malaysian NPC patients. Study designPlasma EBV DNA levels were measured by quantitative PCR (Q-PCR) in a large and multi-ethnic cohort of Malaysian patients with NPC (n=459) and 72 control subjects. ResultsWe show for the first time that, compared to controls, NPC patients with stage I disease had significantly higher levels of EBV DNA (p<0.001). Further, the median level of plasma EBV DNA in stage IV patients with distant metastasis was >9-fold higher than those without systemic spread (p=0.001), suggesting plasma EBV DNA measurement could aid in the diagnosis of metastatic disease in advanced cases. Further, using a cut-off value of 8000copies/mL, we demonstrate that EBV DNA level is a strong predictor for overall survival of NPC patients. ConclusionsOur data show that pre-treatment plasma EBV DNA is a potential biomarker for early stage and metastatic NPC. We conclude that the quantification of plasma EBV DNA is a useful tool in developing countries to stratify patients for MRI or PET/CT scans where such imaging protocol is not routinely applied.

Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy

Plasma Epstein-Barr virus (EBV) DNA is widely used in screening, monitoring, and prediction of relapse in nonmetastatic nasopharyngeal carcinoma (NPC). However, data regarding utility of plasma EBV DNA in metastatic NPC are rare. The current study was to test the prognostic implication of plasma EBV DNA level in metastatic/recurrent NPC patients treated with palliative chemotherapy. Plasma EBV DNA level was measured at baseline and thereafter at the start of each treatment cycle in 127 histologically proven metastatic/recurrent NPC patients treated with palliative chemotherapy. Correlations of pre-treatment and post-treatment plasma EBV DNA levels to survival and response were analyzed. Patients with a low pre-treatment plasma EBV DNA level (<median) had significantly better survival than those with a high pre-treatment plasma EBV DNA level (≥median). Patients with a post-treatment plasma EBV DNA decline to an undetectable level had better survival and better tumor response compared with those with a sustained detectable post-treatment plasma EBV DNA level. The early decrease of post-treatment plasma EBV DNA to an undetectable level after 1 cycle of chemotherapy was associated with significantly increased survival. Patients with low pre-treatment plasma EBV DNA level and undetectable post-treatment plasma EBV DNA showed a favorable prognosis (5-year overall and progression-free survival of 50.6% and 21.7%, respectively). Plasma EBV DNA is of predictive value for prognosis in metastatic/recurrent NPC patients undergoing palliative chemotherapy. The pre-treatment plasma EBV DNA level as well as the early decrease of plasma EBV DNA after chemotherapy enabled easy and early discrimination between patients who will and those who will not benefit from continued treatment.