The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):862-9. doi: 10.1016/j.ijrobp.2015.08.003. Epub 2015 Aug 7.

Abstract

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC).

Patients and methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).

Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020).

Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • DNA, Viral / blood*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / blood*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / radiotherapy
  • Nasopharyngeal Neoplasms / virology
  • Neoadjuvant Therapy
  • Prognosis
  • Time Factors
  • Treatment Failure
  • Treatment Outcome
  • Young Adult

Substances

  • DNA, Viral
  • Cisplatin
  • Fluorouracil