Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients

Kim, Kelly Y.; Le, Quynh‐Thu; Yom, Sue S.; Ng, Raymond; Chan, Kenneth Chun-Ho; Bratman, Scott V.; Welch, John J.; Divi, Rao L.; Petryshyn, Ray; Conley, Barbara A.

doi:10.1016/j.ijrobp.2017.03.018

Cited by 77 publications

(70 citation statements)

References 30 publications

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“…For the past 20 years, the DNA fragment corresponding to the BamHI-W region in the EBV genome has been extensively studied in PCR for quantification of plasma EBV DNA in NPC. [9][10][11][12][13][14][15] Lo et al devised one of the first methodologies of quantifying plasma EBV DNA in 1999 with continuous refinement that is also used in their recent NPC screening study and also our current study. 26 It has been the most accurate biomarker for screening, diagnosis, treatment response monitoring, surveillance for recurrence and prognostication of NPC in endemic areas.…”

Section: Discussionmentioning

confidence: 97%

“…7,8 Plasma Epstein-Barr virus (EBV) DNA has also been shown to be an accurate surrogate marker and has been adopted widely in screening, diagnosis, treatment monitoring and posttreatment surveillance from relapse for NPC for the past two decades. [9][10][11][12][13][14][15] There is a paucity of information on the use of circulating tumor DNA in the past editions of TNM. However, accumulating evidence suggests that plasma EBV DNA carries important prognostic value and that the current TNM staging system is not suited for outcome prediction in patients who are continuously monitored by plasma EBV DNA.…”

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confidence: 99%

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The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

Lee

Kwong

Leung

et al. 2018

Intl Journal of Cancer

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The 8 edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of non-anatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with non-metastatic NPC treated with radical IMRT +/- chemotherapy based on the 8 edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma EBV DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. 5-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066, and p = 0.002 respectively). RPA derived 4 new stages: RPA-I (T1-T4N0-N2 & EBV DNA <500 copies/ml) (PFS 94%, OS 89%, CSS 96%), RPA-II (T1-T4N0-N2 & EBV DNA ≥500 copies/ml) (PFS 80%, OS 83%, CSS 89%), RPA-III (T1-T2N3) (PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4N3) (PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1-T2N0-N2; II: T3-T4N0-N2 or T1-T2N3, and III: T3-T4N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA-based stage groups revealed better survival prediction compared to the 8 edition TNM and the AHR stage groups. This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

Lee

Kwong

Leung

et al. 2018

Intl Journal of Cancer

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“…Outcome of patients with positive EBV DNA was plotted as green curve. 13 While late histological responder is a known observation, 21 it is unclear whether there is also a subgroup of "late responders" in terms of plasma EBV DNA. B, Overall survival (OS) was defined as the time from primary diagnosis to death from any cause.…”

Section: Eight Weeks Post-rtmentioning

confidence: 99%

“…10 However, like many other tumor markers, cell-free EBV DNA is not a perfect biomarker. 12,13 Measurements from different laboratories are typically not directly comparable, imposing difficulty in the interpretation of study results. The kinetics of cell-free EBV DNA is not well understood, and the estimated half-life of plasma EBV DNA differs in radiotherapy (RT) and post-surgical setting.…”

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confidence: 99%

Potential pitfalls in incorporating plasma Epstein‐Barr virus DNA in the management of nasopharyngeal carcinoma

Wong

Hung

2019

Head & Neck

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Background: This study identifies potential pitfalls in incorporating plasma Epstein-Barr virus (EBV) DNA into the management of nasopharyngeal carcinoma (NPC).Methods: A total of 208 NPC patients without distant metastasis who received radical treatment and had measurements of EBV DNA at baseline, 8 weeks and 26 weeks postradiotherapy were analyzed. Prognostic and predictive values at each time-point were compared.Results: Risk stratification by pretreatment level failed to identify a poor prognostic group. Detectable EBV DNA at 8 weeks and 26 weeks postradiotherapy were both associated with significantly poorer 5-year disease-free survival (HR 0.30, P < .001 and HR 0.03, P < .001, respectively) and overall survival (HR 0.27, P = .009 and HR 0.03, P < .001, respectively). Eighty percentage had detectable EBV DNA at recurrence (53.3% for local only, 100% for regional only, and 100% for distant failure).Conclusions: Posttreatment EBV DNA, particularly at 26 weeks post-radiotherapy, has high prognostic and predictive values. Surveillance endoscopy/ imaging are recommended for the detection of local recurrence. K E Y W O R D Sbiomarker, nasopharyngeal carcinoma, pitfalls, plasma EBV DNA, prognostication

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“…EBV has a high exposure rate, with more than 95% of the populations worldwide being infected with EBV [2]. It is well known that EBV causes infectious mononucleosis, a frequent and relatively modest chronic inflammatory syndrome, and it is also related to other diseases and numerous cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma (NPC), and gastric carcinoma (GC) [3].…”

Section: Introductionmentioning

confidence: 99%

Association of the Aquaporin 3 Gene Polymorphism (rs2231231) with Epstein-Barr Virus-Associated Cancers in China

Wang

Zhao

et al. 2018

Intervirology

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Background/Aims: Aquaporins are widely expressed in a variety of cancers and were found to play an important role in cell migration, angiogenesis, tumor formation, and tumor development. Thus, they have been proposed as a potential biomarker for some cancers. Accordingly, we analyzed the association between a single-nucleotide polymorphism locus of aquaporin 3 (rs2231231) and Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (EBVaNPC), lymphoma (EBVaL), and gastric carcinoma in China. Methods: Sequenom MassARRAY technique and polymerase chain reaction sequencing were used to test the genotype of 393 cases of patients with cancer and 148 normal control (NC) samples. A χ² test or correction for continuity or the likelihood ratio was used for statistical analysis, and two-sided p values < 0.05 were considered a statistically significant difference. Results: We found that the genotype distributions were significantly different between either the EBVaNPC group and the NC group or the EBVaL case group and the NC group. However, no statistical associations between rs2231231 and gastric carcinoma was observed in the current study. Conclusions: The AQP3 gene polymorphism is associated with a susceptibility to EBVaNPC and EBVaL, and the homozygous AA genotype is more frequently observed in individuals who develop EBVaNPC and EBVaL.

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Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients

Cited by 77 publications

References 30 publications

The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

Potential pitfalls in incorporating plasma Epstein‐Barr virus DNA in the management of nasopharyngeal carcinoma

Association of the Aquaporin 3 Gene Polymorphism (rs2231231) with Epstein-Barr Virus-Associated Cancers in China

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