ArticleEClinicalMedicine2025
Circulating tumour cells & circulating tumour DNA in patients with resectable colorectal liver metastases (MIRACLE): a prospective, observational biomarker study.
Article in EClinicalMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Impact of methodological variability on the prognostic performance of circulating tumor DNA in colorectal cancer: A systematic review and meta-analysis.The journal of liquid biopsy · 2026Review
- Resect first in resectable colorectal liver metastases: Recalibrating the default.Annals of hepato-biliary-pancreatic surgery · 2026Article
- Noninvasive molecular imaging signatures of histopathological growth patterns in colorectal cancer liver metastases.Clinical & experimental metastasis · 2026Review
- Circulating tumor DNA as a predictive biomarker for prognosis in hepatocellular carcinoma: a systematic review and meta-analysis.Journal of the National Cancer Center · 2026Article
- Presurgical levels of circulating tumour DNA in patients with resectable chemotherapy-naïve colorectal liver metastases: association with multiorgan recurrence and survival in the MIRACLE cohort.The British journal of surgery · 2026Article
- Prognostic value of peri-operative circulating tumour DNA levels estimated by cell-free DNA methylation in patients with resectable colorectal liver metastases.EBioMedicine · 2026Article
- Liquid biopsy biomarkers for early detection of gastrointestinal cancers: Current landscape and emerging technologies.Clinical and translational medicine · 2026Review
- An innovative nuclear antigen-based approach for single-cell isolation of circulating tumor cells in adrenal cortical carcinoma.The journal of liquid biopsy · 2025Article
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Authors and funding
19 authors.
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Abstract
Background: Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need to identify prognostic markers enabling more individualised treatment approaches. Methods: In the MIRACLE, a prospective, observational biomarker study, a total of 188 patients with isolated, resectable CRLM without (neo)adjuvant chemotherapy were included between October 2015 and December 2021. Blood samples were collected before surgery (baseline) and three weeks after surgery. The primary objective was to assess the potential association between postoperative circulating tumour DNA (ctDNA) detection and recurrence of disease for patients with resectable CRLM within one year after resection. The secondary objective was the association between recurrence of disease within one year and detection of circulating tumour cells (CTCs). Baseline ctDNA was measured by next generation sequencing using a targeted panel (Oncomine Colon cell-free DNA assay) and postoperatively by digital PCR on genetic variants found preoperatively with the Oncomine panel. CTCs were enumerated using the FDA-approved CellSearch system. Findings: ctDNA was detected in 117/187 patients (63%) at baseline, and 28/104 evaluable patients (27%) still had detectable ctDNA postoperatively. CTC enumeration resulted in positivity for 37/183 patients (20%) at baseline and 14/158 patients (9%) postoperatively. No association was found between 1-year recurrence-free survival (RFS) and the presence of CTCs or ctDNA at baseline. In contrast, patients with postoperative undetectable ctDNA had a significantly improved 1-year RFS compared to patients with postoperative ctDNA (54% [95% CI 44%-67%] vs. 25% [95% CI 13%-47%], log-rank p = 0.0011). Similarly, patients with postoperative detectable CTCs had a significantly shorter 1-year RFS compared to patients without postoperative CTCs (15% [95% CI 4%-55%] vs. 53% [95% CI 45%-62%], log-rank p 0.0004). Also in multivariable analysis, detectable ctDNA and CTCs after surgery remained independently associated with a shorter 1-year RFS (HR 2.35; 95% CI 1.34-4.11; p = 0.0028 and HR 2.98; 95% CI 1.56-5.71; p = 0.0010, respectively). Interpretation: This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of postoperative detectable circulating tumour load on 1-year RFS. Postoperative ctDNA and CTC detection both represent strong, independent predictors for a shorter RFS after local treatment, as opposed to preoperative detection. Funding: This work was supported by KWF Kankerbestrijding (Dutch Cancer Society, EMCR 2014-6340).
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