BJC-Longitudinal monitoring of circulating tumour DNA improves 2020.pdf (999.56 kB)
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Longitudinal monitoring of circulating tumour DNA improves prognostication and relapse detection in gastroesophageal adenocarcinoma

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journal contribution
posted on 28.09.2020, 11:49 by Mark R Openshaw, Ali A Mohamed, Barbara Ottolini, Daniel Fernandez-Garcia, Cathy J Richards, Karen Page, David S Guttery, Anne L Thomas, Jacqui A Shaw
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.

History

Citation

Br J Cancer (2020). https://doi.org/10.1038/s41416-020-1002-8

Version

VoR (Version of Record)

Published in

British Journal of Cancer

Publisher

Nature Publishing Group

issn

0007-0920

eissn

1532-1827

Acceptance date

08/07/2020

Copyright date

2020

Available date

28/07/2021

Spatial coverage

England

Language

English