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 ◽  
...  

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.

2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  

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.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  

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.


2007 ◽  
Vol 22 (3) ◽  
pp. 194-199 ◽  
Author(s):  
E. Özyar ◽  
M. Gültekin ◽  
A. Alp ◽  
G. Hasçelik ◽  
Ö. Ugur ◽  
...  

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.


2018 ◽  
Vol 11 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Paolo Gamba ◽  
Luigina Rota ◽  
C. Abeni ◽  
Alessandra Huscher ◽  
Gabriele Saldi ◽  
...  

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.


2017 ◽  
Vol 58 (4) ◽  
pp. 509-516 ◽  
Author(s):  
Anussara Prayongrat ◽  
Chakkapong Chakkabat ◽  
Danita Kannarunimit ◽  
Pokrath Hansasuta ◽  
Chawalit Lertbutsayanukul

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.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  

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.


Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3547-3553 ◽  
Author(s):  
Jennifer A. Kanakry ◽  
Hailun Li ◽  
Lan L. Gellert ◽  
M. Victor Lemas ◽  
Wen-son Hsieh ◽  
...  

Key Points Plasma EBV-DNA is highly concordant with EBV tumor status in Hodgkin lymphoma. Plasma EBV-DNA has prognostic significance in Hodgkin lymphoma, both before therapy and at month 6 of follow-up.


2014 ◽  
Vol 66 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Ana Banko ◽  
Ivana Lazarevic ◽  
M. Folic ◽  
Maja Cupic ◽  
Tanja Jovanovic

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease.


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