Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma
Menée sur 107 patients atteints d'un carcinome rhinopharyngé de stade IIB-IV (durée médiane de suivi : 6,2 ans), cette étude met en évidence une association entre le niveau plasmatique d'ADN du virus d'Epstein-Barr à mi-parcours d'un traitement par radiothérapie et la survie des patients
Background : To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at mid-course of chemoradiotherapy (CRT)/ radiotherapy (RT), with respect to the plasma load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC).
Patients and Methods : 107 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 endpoints are post-DNA load, a recognized surrogate of survival, and clinical outcome.
Results : 93% 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 (HR 12.02, 95%CI 2.78-51.93; p<0.0001), progression-free survival (HR 4.05, 95%CI 1.89-8.67, p<0.0001), and overall survival (HR 3.29, 95%CI 1.37-7.90, p=0.0077). 74% 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.
Conclusion : Unfavorable EBV DNA response at mid-course of radiotherapy/ chemoradiotherapy 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 chemoradiotherapy, and adjuvant therapy. Validation studies are awaited.
Annals of Oncology , résumé, 2014