Dataset Information

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

ABSTRACT:

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).

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.

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.

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.

SUBMITTER: Bolhuis K

PROVIDER: S-EPMC8340125 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Bolhuis Karen K van 't Erve Iris I Mijnals Clinton C Delis-Van Diemen Pien M PM Huiskens Joost J Komurcu Aysun A Lopez-Yurda Marta M van den Broek Daan D Swijnenburg Rutger-Jan RJ Meijer Gerrit A GA Punt Cornelis J A CJA Fijneman Remond J A RJA

EBioMedicine 20210729

<h4>Background</h4>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).<h4>Methods</h4>Twenty-three patients were selected from an ongoing phase-3 trial who unde ...[more]

PMID: 34333237

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Project description:Background: It is urgent to develop robust prognostic biomarkers for non-metastatic colorectal cancer (CRC) patients undergoing surgery. The current study aimed to explore and compare the clinical significance of preoperative and postoperative blood tumor biomarkers including circulating tumor cells (CTCs), and develop prognostic models based on tumor biomarkers in patients with stage II-III CRC receiving surgery. Methods: A prospective study was performed to enroll 130 patients with stage II-III CRC receiving surgery between January 2015 and December 2017. Preoperative and postoperative blood tumor biomarkers including CTCs were detected and their prognostic value in predicting tumor recurrence-free survival (RFS) in stage II-III CRC were identified by Kaplan-Meier curves and Cox proportional hazard regression models. Results: CTCs counts within three postoperative days were significantly higher than preoperative CTCs (pre-CTCs). No significant association of pre-CTCs with clinical characteristics and tumor biomarkers was observed while positive postoperative CTCs (post-CTCs) were associated with female, older onset age, high TNM stage, tumor recurrence, and preoperative CEA. Kaplan-Meier curve with log-rank test and univariate Cox proportional hazard regression analysis suggested high N stage, TNM stage, positive pre-carbohydrate antigen (CA) 125, pre-CA19-9, post-CA125, post-CA19-9, post-CA72-4, post-carcinoembryonic antigen (CEA), and post-CTCs were correlated with poor RFS. In multivariate analysis, only TNM stage (adjusted HR=3.786, 95% CI=1.330-10.780; P=0.013), post-CA72-4 (adjusted HR=5.675, 95% CI=2.064-15.604; P=0.001), and post-CTCs (adjusted HR=2.739, 95% CI=1.042-7.200; P=0.041) were significantly correlated with poor RFS. We then developed prognostic models combining post-CTCs and post-CA72-4 with TNM stage or not to stratify the patients into different risk groups. These prognostic models exert a similar good performance in predicting tumor RFS in stage II-III CRC patients. Conclusions: Postoperative CTCs were prior to preoperative CTCs in predicting tumor recurrence survival in non-metastatic CRC patients undergoing surgery. We also developed CTCs-based prognostic models to predict tumor recurrence in stage II-III CRC, which might be used to identify the patients with high risk of recurrence and guide aggressive treatment to improve the clinical outcomes of those patients.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

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