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Ann Oncol. 2014 Jun;25(6):1204-8. doi: 10.1093/annonc/mdu117. Epub 2014 Mar 17.

Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma.

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  • 1Department of Clinical Oncology
  • 2Department of Chemical Pathology.
  • 3Department of Clinical Oncology.
  • 4Department of School of Public Health, State Key Laboratory in Oncology in South China, Sir YK Pao Center for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong.



To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC).


One hundred seven patients with stage IIB-IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome.


Ninety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78-51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89-8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37-7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect.


Unfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:


EBV DNA nasopharyngeal carcinoma

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