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

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.

journal_name

Br J Cancer

authors

Openshaw MR,Mohamed AA,Ottolini B,Fernandez-Garcia D,Richards CJ,Page K,Guttery DS,Thomas AL,Shaw JA

doi

10.1038/s41416-020-1002-8

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1271-1279

issue

8

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-1002-8

journal_volume

123

pub_type

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