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

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


Background: 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).

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: EBV DNA nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Carcinoma
  • Chemoradiotherapy
  • DNA, Viral / blood*
  • Disease-Free Survival
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / complications
  • Female
  • Herpesvirus 4, Human* / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / therapy
  • Nasopharyngeal Neoplasms / virology*
  • Prognosis
  • Proportional Hazards Models
  • Radiation Tolerance
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome
  • Viral Load


  • Biomarkers, Tumor
  • DNA, Viral