scholarly journals Prognostic role of plasma Epstein-Barr virus DNA load for nasopharyngeal carcinoma: a meta-analysis

2017 ◽  
Vol 40 (1) ◽  
pp. 1 ◽  
Author(s):  
Ting-bo Liu ◽  
Zhi-hong Zheng ◽  
Jie Pan ◽  
Li-li Pan ◽  
Li-hong Chen

Purpose: Predicting prognosis and treatment outcomes for patients with for nasopharyngeal carcinoma (NPC) has been difficult due to the heterogeneous nature of the disease This study aimed to evaluate pretreatment copy number of plasma Epstein-Barr virus (EBV) DNA as an outcome marker for survival in NPC. Methods: MEDLINE, CENTRAL and Embase databases were searched until April 7, 2015. Included studies were randomized controlled trials, two-arm prospective studies, or retrospective studies in patients with newly diagnosed NPC. The primary outcome was overall survival and secondary outcomes were progression-free, relapse-free, disease-free and distant metastasis-free survival. Sensitivity, quality and publication bias assessments were performed. Results: Sixteen studies were included in the meta-analysis, with a total of 7698 patients. For overall survival, pooled HR was 3.005 (95% confidence interval [CI] = 2.245–4.022; P < 0.001), indicating that higher levels of EBV DNA were associated with a greater risk of death. Pooled estimates for relapse-free, disease-free, progression-free and distant metastasis-free survival indicated that higher levels of EBV DNA were associated with an increased risk of relapse, disease recurrence, disease progression and distant metastasis in comparison with lower levels of EBV DNA (P values < 0.001). Conclusion: This meta-analysis found that high EBV DNA levels indicate poor prognosis and reduced long-term survival in patients with newly diagnosed NPC; hence, EBV DNA levels are highly prognostic of survival in patients with NPC. None of the included studies used the WHO standard for EBV DNA measurement, indicating a greater need for harmonization in future studies.

2020 ◽  
Author(s):  
Tianzhu Lu ◽  
Qiaojuan Guo ◽  
Keyu Lin ◽  
Honglin Chen ◽  
Yixin Chen ◽  
...  

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.


2001 ◽  
Vol 19 (10) ◽  
pp. 2607-2615 ◽  
Author(s):  
Jin-Ching Lin ◽  
Kuang Y. Chen ◽  
Wen-Yi Wang ◽  
Jian-Sheng Jan ◽  
Wen-Miin Liang ◽  
...  

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC.PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model.RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P = .001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1–positive (n = 88) and those who were EBNA-1–negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1–positive patients and only one of 36 EBNA-1–negative patients developed distant metastases (P = .00015). Kaplan-Meier estimates of overall survival (P = .0010), metastasis-free survival (P = .0004), and progression-free survival (P = .0004) were significantly lower for the patients in the EBNA-1–positive group than for those in the EBNA-1–negative group. Multivariate Cox analysis confirmed the same results.CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.


2017 ◽  
Vol 1 (11) ◽  
pp. 681-684 ◽  
Author(s):  
Jennifer J. G. Welch ◽  
Cindy L. Schwartz ◽  
Meghan Higman ◽  
Lu Chen ◽  
Allen Buxton ◽  
...  

Key Points EBV DNA in cell-free blood in patients with Hodgkin lymphoma correlated with the presence of virus in tumor. Persistence of EBV DNA in cell-free blood 1 week after initiation of therapy predicted inferior event-free survival.


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 ◽  
...  

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.


2018 ◽  
Vol 10 ◽  
pp. 175883591878233 ◽  
Author(s):  
Hu Liang ◽  
Xing Lv ◽  
Lin Wang ◽  
Yi-Shan Wu ◽  
Rui Sun ◽  
...  

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein–Barr virus (EBV) DNA levels. Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders. Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5–155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218–5.216], disease-free survival (HR 2.168, 95% CI 1.349–3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194–4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results. Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Ze-Long Liu ◽  
Xi-Wen Bi ◽  
Pan-Pan Liu ◽  
De-Xin Lei ◽  
Wen-Qi Jiang ◽  
...  

Background. Circulating Epstein-Barr virus (EBV) DNA concentrations were reported to have prognostic value for NK/T-cell lymphoma patients in limited small-scale studies. In this study, we aimed to evaluate the clinical utility of circulating EBV-DNA concentrations to a large sample of NK/T-cell lymphoma patients. Methods. We conducted this meta-analysis, which included a total of 15 prospective and retrospective comparable studies to assess the association between pretreatment EBV-DNA (pre-DNA), posttreatment EBV-DNA (post-DNA), and clinical outcomes of NK/T-cell lymphoma patients. We chose overall survival (OS) as the primary endpoint and progression-free survival (PFS), complete response (CR), and overall response rate (ORR) as secondary endpoints. Results. High pre-DNA and detectable post-DNA were both significantly correlated with poorer OS in NK/T-cell lymphoma patients (P<0.05), with hazard radios (HRs) equal to 3.45 and 2.30, respectively. High pre-DNA and detectable post-DNA also predicted poorer PFS. Additionally, high pre-DNA was found to be significantly correlated with both worse CR and ORR, which indicated worse treatment response. Conclusion. Circulating EBV-DNA concentrations provides prognostic values of survival and treatment response in NK/T-cell lymphoma patients.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Johan S. Nilsson ◽  
Ola Forslund ◽  
Fredrik C. Andersson ◽  
Malin Lindstedt ◽  
Lennart Greiff

Abstract Nasopharyngeal cancer (NPC) is associated with the Epstein-Barr virus (EBV). The clinical presentation and prognosis of NPC is well described, but not in relation to intralesional EBV-DNA load. In a retrospective design, 48 patients with NPC were examined. Patient history was re-evaluated, and diagnostic biopsies were re-examined. Furthermore, intralesional EBV-DNA was quantitated and HPV status determined. Cancer stage, disease-free survival (DFS), and overall survival (OS) were assessed. Of the 48 patients, 36 (75%) patients featured lesions that were positive for EBER (Epstein–Barr virus-encoded small RNA) and 40 (83%) were positive for EBV-DNA. Seven patients (15%) were HPV positive. The levels of EBV-DNA ranged from 0.0005 to 94617 copies/cell. An EBV-DNA load of more than 70 copies/cell was associated with a prolonged DFS for EBV-DNA positive patients treated with curative intent (p = 0.046). In conclusion, the EBV-DNA load in NPC lesions appears to vary greatly. For patients with EBV-DNA positive NPC treated with curative intent, an EBV-DNA load of more than 70 copies/cell is associated with a better outcome in terms of 7-year DFS.


Author(s):  
Xiao-Yun Li ◽  
Dong-Hua Luo ◽  
Ling Guo ◽  
Hao-Yuan Mo ◽  
Rui Sun ◽  
...  

PURPOSE Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, –4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.


2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Haiqin Peng ◽  
Zhanzhan Li ◽  
Yujiao Long ◽  
Jiahui Li ◽  
Zhiyuan Liu ◽  
...  

Abstract Background: To evaluate the diagnostic value of Epstein–Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. Methods: Articles related to the diagnosis of recurrent or metastatic NPC by the detection of EBV DNA in plasma or serum were retrieved from different databases. Sensitivity, specificity, summary receiver operating characteristic (SROC) curves, and likelihood ratios were pooled to assess the diagnostic value of individual diagnostic tests. Results: This meta-analysis pooled 25 eligible studies including 2496 patients with NPC. The sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of EBV DNA in the diagnosis of NPC were 0.858 (95% confidence interval (CI): 0.801–0.901), 0.890 (95% CI: 0.866–0.909), 7.782 (95% CI: 6.423–9.429) and 0.159 (95% CI: 0.112–0.226), respectively. The diagnostic odds ratio (DOR) was 48.865 (95% CI: 31.903–74.845). The SROC for EBV DNA detection was 0.93 (95% CI: 0.90–0.95). Conclusion: The detection of EBV DNA for the diagnosis of recurrent or metastatic NPC has good sensitivity and specificity and might be helpful in monitoring recurrent or metastatic NPC.


2020 ◽  
Vol 12 ◽  
pp. 175883592093205
Author(s):  
Lu-Lu Zhang ◽  
Meng-Yao Huang ◽  
Fei-Xu ◽  
Ke-Xin Wang ◽  
Di Song ◽  
...  

Aim: The present study aimed to evaluate the combined value of locoregional extension patterns (LEPs) and circulating cell-free Epstein–Barr virus (cf EBV) DNA for risk stratification of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) to better guide therapeutic strategies. Methods: A total of 7227 cases of LA-NPC were reviewed retrospectively and classified into six groups according to their LEP (ascending, descending, or mixed type) and pre-treatment cf EBV-DNA load (⩾ versus <4000 copy/ml). Using a supervised statistical clustering approach, patients in the six groups were clustered into low, intermediate, and high-risk clusters. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan–Meier method and differences were compared using the log-rank test. Results: Survival curves for the low, intermediate, and high-risk clusters were significantly different for all endpoints. The 5-year survival rate for the low, intermediate, and high-risk clusters, respectively, were: PFS (83.5%, 73.2%, 62.6%, p < 0.001), OS (91.0%, 82.7%, 73.2%, p < 0.001), DMFS (92.3%, 83.0%, 73.4%, p < 0.001), and LRRFS (91.0%, 88.0%, 83.3%, p < 0.001). The risk clusters acted as independent prognostic factors for all endpoints. Among the patients in the high-risk cluster, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (CCRT) significantly improved the patients 5-year PFS (66.4% versus 57.9%, p = 0.014), OS (77.6% versus 68.6%; p < 0.002), and DMFS (76.6% versus 70.6%; p = 0.028) compared with those treated with CCRT. Conclusion: Our results could facilitate the development of risk-stratification and risk-adapted therapeutic strategies for patients with LA-NPC.


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