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Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases.

Karen Bolhuis ,
Iris van 't Erve ,
Clinton Mijnals ,
Pien M Delis-Van Diemen ,
Joost Huiskens ,
Aysun Komurcu ,
Marta Lopez-Yurda ,
Daan van den Broek ,
Rutger-Jan Swijnenburg ,
Gerrit A Meijer ,
Cornelis J A Punt ,
Remond J A Fijneman

Abstract

METHODS

Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system.

BACKGROUND

Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS).

INTERPRETATION

The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response.

FUNDING

None.

FINDINGS

With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1-9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4-15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS.

More about this publication

EBioMedicine

Volume 70
Pages 103498
Publication date 01-08-2021

Full text links

Publisher website (DOI) 10.1016/j.ebiom.2021.103498
Europe PubMed Central 34333237
Pubmed 34333237

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