title: Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma.
abstract: 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).
  
  
  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.
authors.affiliation: Department of Clinical Oncology sfleung@clo.cuhk.edu.hk.
authors.forename: S F
authors.initials: SF
authors.lastname: Leung
authors.affiliation: Department of Chemical Pathology.
authors.forename: K C A
authors.initials: KC
authors.lastname: Chan
authors.affiliation: Department of Clinical Oncology.
authors.forename: B B
authors.initials: BB
authors.lastname: Ma
authors.affiliation: Department of Clinical Oncology.
authors.forename: E P
authors.initials: EP
authors.lastname: Hui
authors.affiliation: Department of Clinical Oncology.
authors.forename: F
authors.initials: F
authors.lastname: Mo
authors.affiliation: Department of Chemical Pathology.
authors.forename: K C K
authors.initials: KC
authors.lastname: Chow
authors.affiliation: Department of Clinical Oncology.
authors.forename: L
authors.initials: L
authors.lastname: Leung
authors.affiliation: Department of Clinical Oncology.
authors.forename: K W
authors.initials: KW
authors.lastname: Chu
authors.affiliation: Department 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.
authors.forename: B
authors.initials: B
authors.lastname: Zee
authors.affiliation: Department of Chemical Pathology.
authors.forename: Y M D
authors.initials: YM
authors.lastname: Lo
authors.affiliation: Department of Clinical Oncology.
authors.forename: A T C
authors.initials: AT
authors.lastname: Chan
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002277:Carcinoma; D059248:Chemoradiotherapy; D004279:DNA, Viral / Q000097:blood*; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000150:complications; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000628:therapy / Q000821:virology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: EBV DNA nasopharyngeal carcinoma