scholarly journals Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management

2018 ◽  
Vol 11 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Paolo Gamba ◽  
Luigina Rota ◽  
C. Abeni ◽  
Alessandra Huscher ◽  
Gabriele Saldi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Distant Metastases ◽  
Disease Stage ◽  
Diagnostic Model ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response.

scholarly journals Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Disease Stage ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment ◽  
Moroccan Patients

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

scholarly journals Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Program ◽  
Southern China ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

scholarly journals Circulating Plasma Epstein–Barr virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Kaplan Meier ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Landmark Analyses ◽  
Predictive Indicator

Abstract PURPOSE Epstein Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma, while the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan–Meier estimates. 12 and 24-month landmark analyses for OS data were performed according to the EBV groups. RESULTS Patients with post-EBV < 2,500 copies/mL achieved better survival than the higher ones. Furthermore, patients with continuously elevated EBV DNA had significantly poorer OS (HR: 2.542, 95%CI: 2.077–3.111, P < 0.001), DMFS (HR: 2.970, 95%CI: 2.392–3.687, P < 0.001), LRFS (HR: 1.699, 95%CI: 1.072–2.692, P = 0.013), and PFS (HR:2.535, 95%CI: 1.987–3.233, P < 0.001) than patients with continuously normal EBV or those with elevated levels at any time-point. The 5-year OS with elevated EBV was lower than the remission group by the 12 and 24-month landmark analysis. CONCLUSIONS Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis and unfavorable prognosis for NPC. In addition, EBV DNA was predictable no matter how long the follow-up time.

scholarly journals Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes

2019 ◽  
Vol 121 (8) ◽  
pp. 690-698
Author(s):  
John Malcolm Nicholls ◽  
Victor Ho-Fun Lee ◽  
Sik-Kwan Chan ◽  
Ka-Chun Tsang ◽  
Cheuk-Wai Choi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Primary Tumour ◽  
Cancer Specific Survival ◽  
Early Stage Disease ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment

Abstract Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.

Use of Plasma Epstein-Barr virus DNA Monitoring as a Tumor Marker in follow-up of Patients with Nasopharyngeal Carcinoma: Preliminary Results and Report of two Cases

2007 ◽  
Vol 22 (3) ◽  
pp. 194-199 ◽  
Author(s):  
E. Özyar ◽  
M. Gültekin ◽  
A. Alp ◽  
G. Hasçelik ◽  
Ö. Ugur ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Nasopharyngeal Cancer ◽  
Barr Virus ◽  
Group A ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Group B

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77–13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.

scholarly journals Prevalence and significance of plasma Epstein-Barr Virus DNA level in nasopharyngeal carcinoma

2017 ◽  
Vol 58 (4) ◽  
pp. 509-516 ◽  
Author(s):  
Anussara Prayongrat ◽  
Chakkapong Chakkabat ◽  
Danita Kannarunimit ◽  
Pokrath Hansasuta ◽  
Chawalit Lertbutsayanukul
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Treatment Outcomes ◽  
Epstein Barr Virus ◽  
Locally Advanced ◽  
World Health ◽  
Disease Stage ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) DNA has been recognized as a promising tumor marker for nasopharyngeal carcinoma (NPC). This study aims to demonstrate the prevalence of plasma EBV DNA and its temporal correlation with treatment outcomes in the modern era. A total of 204 patients with Stage I–IVB NPC treated with intensity-modulated radiotherapy (IMRT) were enrolled. Quantitative plasma EBV DNA measurement was performed before treatment (pre-IMRT), on the fifth week of radiation (mid-IMRT), at 3 months after radiation (post-IMRT), then every 6 months until disease relapse. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Plasma EBV DNA was detected in 110 patients (53.9%), with a median pre-IMRT EBV DNA level of 8005 copies/ml. Significant correlation was noted between pre-IMRT EBV DNA level and disease stage, but not between pre-IMRT EBV DNA level and World Health Organization classification. With a median follow-up time of 35.1 months, the 3-year PFS and OS rates were higher in the group with undetectable pre-IMRT EBV DNA level compared with in the group in which it was detectable. When classified according to disease stage and pre-IMRT EBV DNA, patients with early disease and detectable pre-IMRT EBV DNA experienced poorer survival than those with locally advanced disease and undetectable pre-IMRT EBV DNA. According to the dynamic changes in EBV DNA level between pre-IMRT and mid/post IMRT, survival was significantly higher in patients who achieved an undetectable level following treatment. On multivariate analysis, post-IMRT EBV DNA level was the strongest predictor of all treatment outcomes (P &lt; 0.001). Our study demonstrated the clinical significance of the plasma EBV DNA level at specific time points, as well as of the dynamic changes in the EBV DNA level. Disappearance of plasma EBV DNA after treatment was associated with better survival.

scholarly journals Circulating Plasma Epstein–Barr virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Dynamic Changes ◽  
Barr Virus ◽  
Kaplan Meier ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Landmark Analyses ◽  
Predictive Indicator

Abstract Background: Epstein Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma, while the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival.Methods: We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan–Meier estimates. 12 and 24-month landmark analyses for OS data were performed according to the EBV groups.Results: Patients with post-EBV < 2,500 copies/mL achieved better survival than the higher ones. Furthermore, patients with continuously elevated EBV DNA had significantly poorer OS (HR: 2.542, 95%CI: 2.077–3.111, P < 0.001), DMFS (HR: 2.970, 95%CI: 2.392–3.687, P < 0.001), LRFS (HR: 1.699, 95%CI: 1.072–2.692, P = 0.013), and PFS (HR:2.535, 95%CI: 1.987–3.233, P < 0.001) than patients with continuously normal EBV or those with elevated levels at any time-point. The 5-year OS with elevated EBV was lower than the remission group by the 12 and 24-month landmark analysis.Conclusions: Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis and unfavorable prognosis for NPC. In addition, EBV DNA was predictable in the long follow-up time.

Prospective Study of Tailoring Whole-Body Dual-Modality [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography With Plasma Epstein-Barr Virus DNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging

2013 ◽  
Vol 31 (23) ◽  
pp. 2861-2869 ◽  
Author(s):  
Lin-Quan Tang ◽  
Qiu-Yan Chen ◽  
Wei Fan ◽  
Huai Liu ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Epstein Barr Virus ◽  
Distant Metastases ◽  
Emission Tomography ◽  
Barr Virus ◽  
Positron Emission ◽  
Pet Ct ◽  
Risk Patients ◽  
Ebv Dna ◽  
Epstein Barr

Purpose To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [18F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. Patients and Methods Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. Results Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low–risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively. Conclusion PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Wing-Yan Au ◽  
Annie Pang ◽  
Carolyn Choy ◽  
Chor-Sang Chim ◽  
Yok-Lam Kwong
Keyword(s):  
Multivariate Analysis ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Disease Stage ◽  
Tumor Biomarker ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Immunocompetent Patients

Abstract In Epstein-Barr-virus (EBV)–positive lymphomas in immunocompetent patients, release of EBV DNA from tumor cells into the plasma might be useful for disease monitoring and prognostication. To test this hypothesis, we quantified serially plasma EBV DNA by quantitative polymerase chain reaction in 39 cases of EBV-positive (natural killer [NK] cell, n = 23; T cell, n = 8; B cell, n = 4; Hodgkin, n = 4) lymphomas. As control, EBV DNA was undetectable in 34 cases of EBV-negative lymphomas at diagnosis and during chemotherapy. In all cases of EBV-positive lymphomas, EBV DNA was detectable (105-1010 copies/mL) at diagnosis. It paralleled the clinical course, with EBV DNA becoming undetectable at remission and remaining elevated in refractory disease. On multivariate analysis, high-presentation EBV DNA (&gt; 7.3 × 107 copies/mL) was significantly associated with an inferior overall survival (OS). Subgroup analysis of NK cell lymphomas, the largest cohort in this study, showed that presentation EBV DNA was correlated with disease stage and lactate dehydrogenase. On multivariate analysis, high-presentation EBV DNA (&gt; 6.1 × 107 copies/mL) was significantly associated with an inferior disease-free survival. During treatment, patients with EBV DNA that showed further increases or failed to become undetectable had significantly inferior OS. In EBV-positive lymphomas, plasma EBV DNA is valuable as a tumor biomarker and for prognostication.

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