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Meta-Analysis
. 2023 Oct 25;12(21):2520.
doi: 10.3390/cells12212520.

Circulating Tumour DNA as Biomarker for Colorectal Liver Metastases: A Systematic Review and Meta-Analysis

Lissa Wullaert  1 , Jan M van Rees  1 , John W M Martens  2 , Henk M W Verheul  2 , Dirk J Grünhagen  1 , Saskia M Wilting  2 , Cornelis Verhoef  1
Affiliations
Meta-Analysis

Circulating Tumour DNA as Biomarker for Colorectal Liver Metastases: A Systematic Review and Meta-Analysis

Lissa Wullaert et al. Cells. .

Abstract

Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27-4.28, p < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53-10.04, p < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13-19.17, p < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.

Keywords: cfDNA (circulating free DNA); colorectal liver metastases (CRLM); ctDNA (circulating tumour DNA); liquid biopsy; minimal residual disease (MRD).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart.
Figure 2
Figure 2
Meta-analysis of the association between recurrence-free survival and the presence of ctDNA preoperatively [20,21,29]. The pooled hazard ratio (black diamond) for ctDNA presence before surgery in CRLM patients is 1.98 (95% CI 1.04–4.36; p = 0.10) compared to patients without detectable ctDNA. A hazard ratio of the study result is represented by a red box. The boxes’ size represents the study’s weight in the analysis. The horizontal line acts as the 95% confidence intervals of the study result, with each end of the line representing the boundaries of the confidence interval. (HR hazard ratio, CI confidence interval).
Figure 3
Figure 3
Meta-analysis of the association between recurrence-free survival and the presence of ctDNA after curative-intent surgery [17,20,24,25,27,28]. The pooled hazard ratio for ctDNA presence after surgery in CRLM patients is 3.12 (95% CI 2.27–4.28; p < 0.00001) compared to patients without detectable ctDNA.
Figure 4
Figure 4
Meta-analysis of the association between recurrence-free survival and the presence of ctDNA after end of adjuvant treatment [17,24,27]. The pooled hazard ratio for ctDNA presence at the end of adjuvant chemotherapy in CRLM patients was 6.39 (95% CI 2.13–19.17; p = 0.0009) compared to patients without detectable ctDNA.
Figure 5
Figure 5
Meta-analysis of the association between overall survival and the presence of ctDNA preoperatively [17,20,26,29]. The pooled hazard ratio for ctDNA presence before surgery in CRLM patients was 4.04 (95% CI 0.98–16.61; p = 0.05) compared to patients without detectable ctDNA.
Figure 6
Figure 6
Meta-analysis of the association between overall survival and the presence of ctDNA after curative-intent surgery [20,27,28]. The pooled hazard ratio for ctDNA presence after surgery in CRLM patients is 5.04 (95% CI 2.53–10.04; p < 0.00001) compared to patients without detectable ctDNA.
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