Evidence map›Paper›PMID 41905259›Full record

ArticleEBioMedicine2026

Prognostic value of peri-operative circulating tumour DNA levels estimated by cell-free DNA methylation in patients with resectable colorectal liver metastases.

Stavros Makrodimitris, Lissa Wullaert, Daan Hazelaar, Teoman Değer, Ruben G Boers, Mark A van de Wiel, Maurice Phm Jansen, Jaco Kraan, Joachim B Boers, Wilfred Fj van IJcken and 12 more

Abstract read
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Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

22 authors.

Stavros MakrodimitrisMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Lissa WullaertSurgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Daan HazelaarMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Teoman DeğerMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Ruben G BoersDevelopmental Biology, Erasmus University Medical Center, the Netherlands.
Mark A van de WielEpidemiology and Data Science, Amsterdam Public Health, Amsterdam University Medical Center, the Netherlands.
Maurice Phm JansenMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Jaco KraanMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Joachim B BoersDevelopmental Biology, Erasmus University Medical Center, the Netherlands.
Wilfred Fj van IJckenErasmus Center for Biomics, Erasmus University Medical Center, the Netherlands.
Corine M BeaufortMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Vanja de WeerdMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Stefan SleijferMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Joost GribnauDevelopmental Biology, Erasmus University Medical Center, the Netherlands.
Maarten VermaasDepartment of Surgical Oncology and Gastrointestinal Surgery, IJsselland Hospital, the Netherlands.
Eric Jt BeltDepartment of Surgical Oncology and Gastrointestinal Surgery, Albert Schweitzer Hospital, the Netherlands.
Paul D GobardhanDepartment of Surgical Oncology and Gastrointestinal Surgery, Amphia Hospital, the Netherlands.
Henk Mw VerheulMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Dirk J GrűnhagenSurgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
John Wm MartensMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Cornelis VerhoefSurgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands.
Saskia M WiltingMedical Oncology Erasmus MC Cancer Institute, Erasmus University Medical Center, the Netherlands. Electronic address: s.wilting@erasmusmc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHalf of the patients with colorectal liver metastases (CRLM) that undergo local treatment with curative intent experience recurrence within one year. New biomarkers are needed to stratify patients before and/or after surgery to minimise both over- and under-treatment with peri-operative chemotherapy.

methodsWe profiled 120 patients with CRLM not treated with (neo-)adjuvant chemotherapy using a combined assay for genome-wide cell-free DNA methylation and copy number profiling both pre-operatively and three weeks after local treatment of CRLMs. These data were used to estimate the proportion of circulating tumour DNA (ctDNA) in these patients using data from healthy controls and CRLM tissues for reference. The prognostic value of pre-operative and post-operative ctDNA load was assessed on Recurrence-Free Survival (RFS) and Overall Survival (OS) using Cox proportional hazards models.

findingsThe ctDNA estimates based on both DNA methylation and copy numbers were significantly correlated with mutation-based ctDNA fractions and captured tumour-derived information, such as tumour size. The continuous ctDNA amount estimated using methylation was an independent, pre-operative prognostic marker for both RFS (HR = 1.20, 95% CI = [1.03, 1.39], p-value = 0.019) and OS (HR = 1.31, 95% CI = [1.10, 1.55], p-value = 0.002) after accounting for age, sex, Fong risk score, primary tumour location and metastasis timing. Elevated ctDNA levels post-operatively were significantly associated with shorter RFS (p-value = 0.03), but not OS (p-value = 0.16).

interpretationThis study demonstrated the prognostic value of pre-operative and post-operative ctDNA in a homogeneous, chemotherapy-naïve cohort of patients with CRLM as well as its potential to guide decisions on administering peri-operative chemotherapy.

fundingDutch Cancer Society, Dutch Digestive Health Fund.

Indexed as

Biomarkers, TumorCirculating Tumor DNAColorectal NeoplasmsDNA MethylationLiver NeoplasmsAdultAgedDNA Copy Number VariationsFemaleHumansMaleMiddle AgedPrognosisBiomarkers, TumorCirculating Tumor DNAColorectal liver metastasisCopy number variationDNA methylationLiquid biopsyPrognostic biomarkers

Identifiers

PMID41905259
PMCPMC13054272

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.