Longitudinal monitoring of circulating tumour DNA improves prognostication and relapse detection in gastroesophageal adenocarcinoma

Br J Cancer. 2020 Oct;123(8):1271-1279. doi: 10.1038/s41416-020-1002-8. Epub 2020 Jul 28.

Abstract

Background: Gastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker.

Methods: Forty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by targeted next-generation sequencing to identify somatic single-nucleotide variants (SNVs), and Nanostring nCounter® to detect copy number alterations (CNAs). Patient-specific SNVs and CNA amplifications (CNAamp) were analysed in plasma using digital droplet PCR and quantitative PCR, respectively.

Results: Thirty-five patients (13 palliative, 22 curative) had ≥1 SNVs and/or CNAamp detected in primary tumour DNA suitable for tracking in plasma. Eighteen of 35 patients (nine palliative, nine curative) had ≥1 ctDNA-positive plasma sample. Detection of postoperative ctDNA predicted short RFS (190 vs 934 days, HR = 3.7, p = 0.028) and subsequent relapse (PPV for relapse 0.83). High ctDNA levels (>60.5 copies/ml) at diagnosis of metastatic disease predicted poor OS (90 vs 372 days, HR = 11.7 p < 0.001).

Conclusion: Sensitive ctDNA detection allows disease monitoring and prediction of short OS in metastatic patients. Presence of ctDNA postoperatively predicts relapse and defines a 'molecular relapse' before overt clinical disease. This lead time defines a potential therapeutic window for additional anticancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Aged
  • Aged, 80 and over
  • Circulating Tumor DNA / blood*
  • DNA Copy Number Variations
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Prognosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality

Substances

  • Circulating Tumor DNA