Plasma epstein‐barr virus DNA concentration and clearance rate as novel prognostic factors for metastatic nasopharyngeal carcinoma

Hsu, Cheng‐Lung; Chang, Kai‐Ping; Lin, Chien‐Yu; Chang, Hsien‐Kun; Wang, Cheng‐Hsu; Lin, Tung‐Liang; Liao, Chun‐Ta; Tsang, Ngan‐Ming; Lee, Li‐Yu; Chan, Sheng-Chieh; Ng, Shu‐Hang; Li, Hsin‐Pai; Chang, Yu‐Sun

doi:10.1002/hed.21890

Cited by 62 publications

(66 citation statements)

References 23 publications

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“…EBV-DNA may be detected in NPC cells (5,6), and cell-free EBV-DNA may be detected in the plasma of patients with NPC (7)(8)(9)(10)(11)(12)(13). Furthermore, the levels of plasma EBV-DNA in recently diagnosed NPC patients have been significantly correlated with tumor volume (14,15), response to treatment (16), tumor clearance (17,18) and tumor recurrence (19)(20)(21). Similarly, it has been observed that a positive post-treatment detection of plasma EBV-DNA is predictive of poor outcomes in terms of subsequent relapse rate, overall survival (OS) and relapse-free survival (RFS) (11,13).…”

Section: Introductionmentioning

confidence: 99%

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma

et al. 2015

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Abstract. The level of Epstein-Barr virus DNA (EBV-DNA) in the plasma prior and subsequent to treatment is a reliable biomarker for the screening, diagnosis, monitoring and prognosis of nasopharyngeal carcinoma (NPC). The present retrospective study aimed to determine whether pre-and post-treatment levels of plasma EBV-DNA were predictive of survival in a large sample of patients with NPC. The level of plasma EBV-DNA in 637 NPC patients prior and subsequent to treatment was determined by quantitative polymerase chain reaction. The value of pre-and post-treatment plasma EBV-DNA in predicting the survival of NPC patients was then analyzed. The results revealed that pre-treatment plasma EBV-DNA loads were significantly higher in patients with NPC than those in healthy controls (P<0.001). The percentage of patients with positive plasma EBV-DNA was markedly higher prior to treatment (70.64%; median, 1150 copies/ml; range, 0-9.75x10 6 copies/ml) than following treatment (25.99%; median, 0 copies/ml; range, 0-3.83x10 6 copies/ml) (P<0.001). Patients with a high plasma EBV-DNA load presented with a higher clinical tumor classification, lymph node status, metastatic status and overall cancer stage. The risk of NPC relapse and mortality was higher in patients with pre-treatment plasma EBV-DNA levels of ≥1,500 copies/ml than that in patients with <1,500 copies/ml. Furthermore, the risk of relapse and mortality was higher in patients with positive post-treatment plasma EBV-DNA than in patients with negative post-treatment plasma EBV-DNA. Detectable post-treatment plasma EBV-DNA was the most significant prognostic factor to affect relapse-free survival, whilst metastasis was the prognostic factor with the greatest effect on overall survival. These data indicated that pre-and post-treatment levels of plasma EBV-DNA were able to predict the prognosis of NPC. This finding may provide novel references for research and clinical practice.

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Section: Introductionmentioning

confidence: 99%

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma

et al. 2015

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“…The meta-analysis found that high pre-treatment levels of EBV DNA had good value as a prognostic indicator of survival and disease outcomes in patients with NPC. Most of the studies included in this meta-analysis found that increased levels of EBV DNA prior to treatment was associated with poor overall survival [13,[28][29][30][32][33][34][35][36][37]39,40]. Of the studies that evaluated the other outcomes, high pre-treatment EBV DNA levels was also associated with increased risk for disease progression, relapse, recurrence, and distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…The remaining 57 were fully evaluated for inclusion and 41 were eliminated for not reporting the outcomes of interest, reporting data that could not be pooled for a meta-analysis, not being relevant or reporting findings from a study that was already included. Sixteen studies were included in the study with a total of 7698 patients [12,13,[28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Three of the studies were retrospective in design and the remaining 13 studies were prospective (Table 1).…”

Section: Literature Searchmentioning

confidence: 99%

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

Liu

Zheng

Pan³

et al. 2017

CIM

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

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“…The drop in viral DNA in the blood during RT/CHRT was accompanied by remission of NPC as a response to treatment [21]. Patients with more rapid clearance of EBV DNA from the circulation responded better to treatment and had a better survival probability [22,23]. Due to high sensitivity and specificity [24,25], plasma EBV DNA has been adopted as a marker for clinical management of patients with NPC [26].…”

Section: Discussionmentioning

confidence: 99%

Post-Treatment Circulating Free HPV DNA As a Marker of Treatment Outcome in Patients with HPV-Related Propharyngeal Cancer After Radio(chemo)therapy

Tw¹,

Mazurek²,

Ånietura³

et al. 2017

Cell Mol Med

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Circulating cell-free HPV16 DNA (cfHPV DNA) assessed after treatment completion was tested as a prognostic marker of treatment failure in patients with HPVrelated oropharyngeal cancer (OPC) treated with radiotherapy alone (RT) or radiotherapy combined with chemotherapy (CHRT). Fifty-five patients with OPC in whom cfHPV DNA was found prior to RT/CHRT were included into the study. cfHPV DNA was subsequently assessed after treatment completion. cfHPV DNA remission (cfHPVrem) was defined as the absence of cfHPV DNA after treatment completion. The association between cfHPVrem and the risk of local, nodal or distant failure was calculated. Survival curves were calculated according to the Kaplan-Meier technique and compared according to cfHPVrem after treatment completion with the log-rank test. Thirteen (24%) patients presented no cfHPVrem after treatment completion. For these patients, the risk of nodal failure was significantly higher (HR=9.38, 95% CI: 1.63-53.97, p=0.009) than for patients with cfHPVrem. The probability of dissemination was comparable in patients with cfHPVrem and with no cfHPVrem (p=0.95). For patients with HPV related OPC, who has no cfHPVrem after RT/CHRT completion stricter follow up is proposed due to higher risk of nodal failure.

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Plasma epstein‐barr virus DNA concentration and clearance rate as novel prognostic factors for metastatic nasopharyngeal carcinoma

Abstract: The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome.

Cited by 62 publications

References 23 publications

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma

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

Post-Treatment Circulating Free HPV DNA As a Marker of Treatment Outcome in Patients with HPV-Related Propharyngeal Cancer After Radio(chemo)therapy

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