Relationship of circulating tumor cells and Epstein-Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients

Int J Cancer. 2019 Nov 15;145(10):2873-2883. doi: 10.1002/ijc.32380. Epub 2019 Jun 10.

Abstract

We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.

Keywords: Epstein-Barr virus DNA; circulating tumor cells; diagnosis; metastatic nasopharyngeal carcinoma; outcome prediction.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / blood
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / mortality*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / blood
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / mortality*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplastic Cells, Circulating*
  • Predictive Value of Tests
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Viral