Optimal plasma pretreatment EBV DNA cut-off point for nasopharyngeal cancer patients treated with intensity modulated radiation therapy

Jpn J Clin Oncol. 2018 May 1;48(5):467-475. doi: 10.1093/jjco/hyy027.

Abstract

Objective: Plasma Epstein-Barr virus (EBV) DNA concentration at the time of diagnosis (pre-EBV) can be used to stratify risk for nasopharyngeal cancer (NPC) patients. However, pre-EBV cut-off values vary among studies.

Methods: This was a post hoc analysis of 208 NPC patients from a phase II/III study comparing sequential (SEQ) vs. simultaneous integrated boost (SIB) intensity modulated radiation therapy. The objective was to identify the optimal pre-EBV cut-off value to predict overall survival (OS), progression free survival (PFS) and distant metastatic free survival (DMFS) rates.

Results: The pre-EBV and post-treatment EBV DNA (post-EBV) were detectable in 59.1% and 3.8% of the patients, respectively. A new pre-EBV cut-off value of 2300 copies/ml was identified by the receiver operating characteristics analysis. This cut-off value showed 82% sensitivity, 59% specificity and 31.7% positive and 93.5% negative predictive values in predicting OS. The 3-year OS, PFS and DMFS were 95.6 vs. 73.8%, 89.8 vs. 55.3% and 93 vs. 70.1% for pre-EBV < vs. ≥2300 copies/ml, respectively. Older age group (≥45 years), high pre-EBV and detectable post-EBV concentration were independent predictors for OS, PFS and DMFS in a multivariate analysis. When the stage grouping and pre-EBV value were combined, a subgroup of patients with stage II-III and pre-EBV values <2300 copies/ml. had the best survival outcomes, while the worst survival subgroup was the patients with stage III-IVb with pre-EBV values ≥2300 copies/ml.

Conclusions: Pre-EBV cut-off of 2300 copies/ml is an optimal value predicting OS, PFS and DMFS.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Disease-Free Survival
  • Epstein-Barr Virus Infections / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Prognosis
  • Prospective Studies
  • Radiotherapy, Intensity-Modulated / methods*