ctDNA as a biomarker of progression in oesophageal adenocarcinoma

ESMO Open

article

V.F. Bonazzi¹  L.G. Aoude¹  S. Brosda¹  J.M. Lonie¹  K. Patel¹  J.J. Bradford¹  L.T. Koufariotis²  S. Wood²  B. Mark Smithers³  N. Waddell²  A.P. Barbour¹ 

[1] The University of Queensland Diamantina Institute, The University of Queensland;QIMR Berghofer Medical Research Institute;Princess Alexandra Hospital;Faculty of Medicine, University of Queensland

关键词: ctDNA;    sequencing;    biomarker;    oesophageal adenocarcinoma;    survival;    prognostic;   

DOI  :  10.1016/j.esmoop.2022.100452

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.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.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.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.

【 授权许可】

CC BY|CC BY-NC-ND