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ctDNA as a biomarker of progression in oesophageal adenocarcinoma.

Authors :
Bonazzi VF
Aoude LG
Brosda S
Lonie JM
Patel K
Bradford JJ
Koufariotis LT
Wood S
Smithers BM
Waddell N
Barbour AP
Source :
ESMO open [ESMO Open] 2022 Jun; Vol. 7 (3), pp. 100452. Date of Electronic Publication: 2022 Mar 23.
Publication Year :
2022

Abstract

Background: The incidence of oesophageal adenocarcinoma (OAC) is rapidly increasing and despite improvements in treatment, the 5-year survival rate remains poor. Prognostic biomarkers that address the genomic heterogeneity in this highly complex disease will aid the development of precision therapeutics and improve patient survival. The aim of this study was to determine whether circulating tumour DNA (ctDNA) has prognostic significance as a biomarker in OAC patients.<br />Patients and Methods: We profiled 209 blood and tumour samples from 57 OAC patients. Using a panel of 77 cancer genes, we sequenced ctDNA in plasma samples (n = 127) which were taken at multiple time points before and after therapy. In parallel, we sequenced matched tumour samples from 39 patients using the same gene panel. To assess whether the ctDNA profile reflected the tumour heterogeneity, we sequenced additional multi-region primary tumour samples in 17 patients. In addition, we analysed whole-genome and whole-exome sequencing data from primary tumours for a subset of 18 patients.<br />Results: Using a tumour-agnostic approach, we found that detectable ctDNA variants in post-treatment plasma samples were associated with worse disease-specific survival. To evaluate whether the ctDNA originated from the primary tumour, we carried out a tumour-informed analysis which confirmed post-treatment ctDNA variants were associated with worse survival. To determine whether ctDNA could be used as a clinical follow-up test, we assessed blood samples from multiple time points before and after treatment, in a subset of patients. Results showed that the variant allele frequency of ctDNA variants increased with disease recurrence.<br />Conclusion: This study demonstrates that ctDNA variants can be detected in patients with OAC and this has potential clinical utility as a prognostic biomarker for survival.<br />Competing Interests: Disclosure AB received a Roche Investigator initiated clinical research grant. NW is a co-founder and board member of genomiQa. All other authors have declared no conflicts of interest. Data sharing The data that support the findings of this study are available in the European Genome-phenome Archive, study ID EGAS00001002864, dataset ID EGAD00001008554. EGA identifiers can be found in Supplementary Table S1, available at https://doi.org/10.1016/j.esmoop.2022.100452.<br /> (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Details

Language :
English
ISSN :
2059-7029
Volume :
7
Issue :
3
Database :
MEDLINE
Journal :
ESMO open
Publication Type :
Academic Journal
Accession number :
35798469
Full Text :
https://doi.org/10.1016/j.esmoop.2022.100452