scholarly journals Analysis of Plasma Epstein-Barr Virus DNA in Nasopharyngeal Cancer After Chemoradiation to Identify High-Risk Patients for Adjuvant Chemotherapy: A Randomized Controlled Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3091-3100 ◽  
Author(s):  
Anthony T.C. Chan ◽  
Edwin P. Hui ◽  
Roger K.C. Ngan ◽  
Stewart Y. Tung ◽  
Ashley C.K. Cheng ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Adjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Epstein Barr Virus ◽  
Controlled Trial ◽  
Nasopharyngeal Cancer ◽  
Barr Virus ◽  
Randomized Controlled ◽  
Ebv Dna ◽  
Epstein Barr

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.

scholarly journals Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Viral Load ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Tumor Volume ◽  
Nasopharyngeal Cancer ◽  
Dna Quantification ◽  
Barr Virus ◽  
Nasopharyngeal Biopsy ◽  
Ebv Dna ◽  
Epstein Barr

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

Diagnostic and prognostic performance of circulating levels of the Epstein-Barr virus microRNAs BART 7-3p and BART 13-3p in nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Tianzhu Lu ◽  
Qiaojuan Guo ◽  
Keyu Lin ◽  
Honglin Chen ◽  
Yixin Chen ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Distant Metastasis ◽  
Plasma Levels ◽  
Epstein Barr Virus ◽  
Cox Regression ◽  
Prognostic Performance ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Circulating Levels

Abstract Background Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV BamHI A rightward transcripts (BART) encode microRNAs (EBV-miR-BARTs) abnormally highly expressed and play an essential role in NPC. Our previous study indicated that circulating EBV-miR-BARTs was potentially severed as a biomarker of NPC. This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Methods Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. Results Plasma EBV DNA was detected in 93.7% of NPC subjects vs. 8.6% of controls. The microRNAs BART7-3p and miR-BART13-3p were detected in 96.1% and 97.9% of NPC subjects vs. 3.39% and 3.3% of controls. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV-DNA were independent risk for shorter distant metastasis-free survival (DMFS) (HR=2.94, 95%CI: 1.44-5.97, p=0.003; HR=2.27, 95%CI:1.26-4.10, p=0.006) in multivariate Cox regression. In the 245 patients who received radiotherapy, EBV DNA, miR-BART7-3p, and miR-BART13-3p were detectable immediately afterward in, respectively, 28.6%, 17.6%, and 54.7% of patients. Four-year DMFS rate was lower in patients with detectable miR-BART7-3p (73.0% vs. 89.7%, p<0.001), miR-BART13-3p (61.4% vs. 90.0%, p<0.001), and EBV-DNA (82.7% vs. 89.5%, p=0.035) after radiotherapy. In multivariate Cox regression, detectable miR-BART7-3p and EBV-DNA were independent risks for shorter DMFS (HR=4.13, 95%CI: 1.89-9.01, p<0.001; HR = 2.14, 95%CI: 1.04-4.42, p=0.039). Four-years DMFS rate was 92.0% in subjects (n=156) with neither detectable miR-BART7-3p nor EBV-DNA after radiotherapy, 80.0% in subjects (n=65) with either detectable miR-BART7-3p or EBV-DNA after radiotherapy, and 52.9% in subjects (n=24) with both detectable miR-BART7-3p and EBV-DNA after radiotherapy (p<0.001). Conclusions Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy may help stratify patients by risk of poor DMFS.

Is there a correlation between serum Epstein-Barr virus DNA level and tumor metabolic activity, TNM staging and tumor load in nasopharyngeal cancer patients?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17543-e17543 ◽  
Author(s):  
Aysel Ahmedova ◽  
Kubra Ozkaya ◽  
Makbule Tambas ◽  
Ugur Gezer ◽  
Emre Ozgur ◽  
...  
Keyword(s):  
Copy Number ◽  
Epstein Barr Virus ◽  
Tumor Volume ◽  
Nasopharyngeal Cancer ◽  
Significant Relation ◽  
Dna Copy Number ◽  
Barr Virus ◽  
Pet Ct ◽  
Ebv Dna ◽  
Epstein Barr

e17543 Background: To investigate the relationship between pretreatment Epstein-Barr virus (EBV) DNA copy number and tumor metabolic activity, TNM stage and tumor volume in nasopharyngeal cancer (NPC) patients. Methods: Blood samples were collected 0-3 weeks before treatment and number of EBV DNA copies were determined by PCR . MRI and PET-CT were performed 0-4 weeks before treatment. The primary tumor volume (TVnp) and total volume of metastatic lymph nodes (TLV) were delineated separately on MRI by the same radiologist by the aid of program “Osirix” and recorded in cm3. Maximum SUV values of primary tumor (Tsuv) and metastatic lymph nodes (LNsuv) were determined with each PET-CT images. Kruskal Wallis test and Spearman's Correlation Analysis were used for the comparison of 3 or more groups with no normal distribution and the evaluation of the inter-parameter relations, respectively. Results: The study included 50 NPC patients treated between 2011 and 2015. There was no significant relation between serum EBV DNA copy number and the distribution of T stage (p = 0.81), N stage (p = 0.08), TVnp (r:0.009; p = 0.95), and Tsuv (r:-0.007, p = 0.96). However, a significant correlation was detected between EBV DNA copy number and both LNsuv (r:0.337; p = 0.017) and TLV (r:0.579; p = 0.001) (LNsuv and TLV increased as virus load increased). Conclusions: There is no significant relation between pretreatment EBV DNA load and T and N stages and TVnp in NPC patients. However, EBV DNA load has a significant correlation with TLV and LNsuv. These results may imply that TLV can be included in nodal staging and together with LNsuv be integrated in treatment planning.[Table: see text] [Table: see text]

scholarly journals Markers of Epstein–Barr virus in clinical assessment of Russian patients with nasopharyngeal cancer

2021 ◽  
Vol 8 (3) ◽  
pp. 14-24
Author(s):  
K. V. Smirnova ◽  
N. B. Senuta ◽  
I. V. Botezatu ◽  
A. V. Ignatova ◽  
T. E. Dushenkina ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Clinical Significance ◽  
Clinical Condition ◽  
Epstein Barr Virus ◽  
Nasopharyngeal Cancer ◽  
Viral Dna ◽  
Barr Virus ◽  
Iga Antibodies ◽  
Ebv Dna ◽  
Epstein Barr

Introduction. Epstein–Barr virus (EBV) is equally widespread in the endemic and non-endemic world regions for nasopharyngeal cancer (NPC). High incidence of NPC in endemic countries and low in non-endemic countries suggest there are different mechanisms and conditions for tumor occurrence and, possibly, different clinical significance of EBV-associated markers. However, significance of these markers for determining NPC in non-endemic regions is still poorly understood. Objective – to determine clinical significance of titers of IgG/IgA antibodies to EBV capsid antigen and concentrations of the viral DNA in patients’ blood plasma as diagnostic and monitoring markers for NPC in a non-endemic region of Russia. Materials and methods. Titers of EB-specific antibodies were determined by indirect immunofluorescence, and concentration of the viral DNA in plasma was measured using a quantitative polymerase chain reaction in real time. Study group included patients with NPC (n = 96), and control group – blood donors (n = 171) and patients with other head and neck tumors (n = 33).Results. Titers of IgG/IgA antibodies to EBV capsid antigen, being an important diagnostic marker of nasopharyngeal cancer, did not always correlate with patients’ clinical condition. Humoral response to emerging events often delayed due to inertia of the immune system. Concentration of EBV DNA in patients’ blood plasma clearly reflected the dynamics of the pathological process: it decreased to background values in remission and increased while the disease progressed. In contrast to endemic regions, we did not find any correlation between the studied EBV markers and clinical manifestations of the disease, evaluated in accordance with the TNM classification (Tumor, Nodus and Metastasis).Conclusion. In non-endemic countries, such as Russia, serological and molecular markers of EBV can be successfully used for the primary diagnosis of NPC. However, for the disease monitoring, it is preferable to use the value of the concentrations of circulating EBV DNA, which, in contrast to the values of IgG/IgA antibody titers to VCA EBV, more accurately reflect the patient’s clinical condition.

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