Individualized concurrent chemotherapy by pretreatment plasma Epstein-Barr viral DNA in II-III stage nasopharyngeal carcinoma: A propensity score matching analysis using a large cohort

Cancer Med. 2019 Aug;8(9):4214-4225. doi: 10.1002/cam4.2343. Epub 2019 Jun 18.

Abstract

Object: To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II-III nasopharyngeal carcinoma (NPC) patients with different Epstein-Barr virus (EBV) DNA level in intensity-modulated radiotherapy (IMRT) era.

Methods: A total of 2742 patients diagnosed with stage II-III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut-off value of pre-DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level.

Results: In our cohort, the cut-off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695-0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3-year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high-risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low-risk patients (EBV DNA level ≤1460 copies/mL).

Conclusion: Pre-EBV DNA could be a useful tool to guide individualized treatment for stage II-III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre-EBV DNA, while those with low pre-EBV DNA could not.

Keywords: Epstein-Barr virus; chemotherapy; nasopharyngeal carcinoma; overall survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Viral / blood*
  • Drug Therapy
  • Epstein-Barr Virus Infections / diagnosis*
  • Epstein-Barr Virus Infections / drug therapy
  • Epstein-Barr Virus Infections / radiotherapy*
  • Female
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / radiotherapy*
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Staging
  • Precision Medicine
  • Propensity Score*
  • Radiotherapy, Intensity-Modulated
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • DNA, Viral