Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study

Cancer Cell. 2024 Aug 12;42(8):1401-1414.e4. doi: 10.1016/j.ccell.2024.07.001. Epub 2024 Jul 25.

Abstract

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

Keywords: EP-SEASON study; cell-free EBV DNA; changing dynamics; longitudinal circulating tumor DNA; nasopharyngeal carcinoma; real-time recurrence risks.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Circulating Tumor DNA* / blood
  • Circulating Tumor DNA* / genetics
  • DNA, Viral / blood
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Liquid Biopsy / methods
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma* / blood
  • Nasopharyngeal Carcinoma* / diagnosis
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / virology
  • Nasopharyngeal Neoplasms* / blood
  • Nasopharyngeal Neoplasms* / diagnosis
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / virology
  • Neoplasm Recurrence, Local* / blood
  • Neoplasm Recurrence, Local* / genetics
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • DNA, Viral