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Clinical Studies

ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer

British Journal of Cancer volume 132, pages 814–821 (2025)Cite this article

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Abstract

Background

Circulating tumor DNA variations (∆ctDNA) were reported to be associated with treatment efficacy in metastatic colorectal cancer (mCRC). The present study evaluated ∆ctDNA according to first-line treatment intensity.

Methods

Patients from two prospective ctDNA collections were divided into Group ≤ 2 drugs and Group ≥ 3 drugs. ∆ctDNA were analysed from baseline to cycle 3 or 4 (C3-4) according to three predefined subgroups: ∆ctDNA ≥ 80%_ undetectable, ∆ctDNA ≥ 80%_ detectable, and ∆ctDNA < 80%. Impact of ∆ctDNA on progression-free survival (PFS) and overall survival (OS) were analysed.

Results

Pretreatment ctDNA was detected in 129/152 (84.9%) of patients. A ∆ctDNA ≥ 80%_undetectable was more frequent in Group ≥ 3 than ≤ 2 drugs (respectively 51.5% vs. 32.7%, p = 0.015). Patients with ∆ctDNA ≥ 80%_undetectable had longer survival than other ∆ctDNA subgroups, in Group ≥ 3 drugs (mPFS 11.5 vs 7.8 vs 6.3 months, p = 0.02: mOS 30.2 vs 18.1 vs 16.4 month, p = 0.04) and in Group ≤ 2 drugs (mPFS 8.4 vs 6.0 vs 5.3 months, p = 0.05; mOS 29.6 vs 14.6 vs 14.6 months, p = 0.007).

Discussion

Early ∆ctDNA are associated to treatment intensity in first line mCRC with a significant impact on prognosis.

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Fig. 1: Flow chart of the study.
Fig. 2: ctDNA variations according to treatment group and mutational status.
Fig. 3: PFS according to ctDNA variation and treatment group.
Fig. 4: OS according to ctDNA variation and treatment group.

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Data availability

The data presented in the current study are available upon reasonable request from the corresponding author.

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Funding

The authors received no specific funding for this work.

Author information

Author notes

  1. These authors contributed equally: Adrien Grancher, Ludivine Beaussire-Trouvay.

Authors and Affiliations

  1. Normandie Univ, UNIROUEN, Inserm U1245, IRON group, Normandy Centre for Genomic and Personalized Medicine and Department of Hepato-gastroenterology and Digestive Oncology, Rouen University Hospital, Rouen, France

    Adrien Grancher, Virginie Vernon, Marie Dutherage, Pierre Michel, David Sefrioui & Frédéric Di Fiore

  2. Normandie Univ, UNIROUEN, Inserm U1245, IRON group, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France

    Ludivine Beaussire-Trouvay & Nasrin Vasseur

  3. CHI Elbeuf, Department of Hepatogastroenterology, Elbeuf, France

    Valérie Blondin & Caroline Elie

  4. Department of Hepatogastroenterology, Caen University Hospital, Caen, France

    Karine Bouhier-Leporrier & Anne-Laure Bignon

  5. Department of Hepatogastroenterology, Francois Baclesse Centre, Caen, France

    Marie-Pierre Galais & Aurélie Parzy

  6. Department of Biostatistics, Rouen University Hospital, Rouen, France

    Tifenn Clabaut & André Gilibert

  7. Clinique du Cèdre, Bois-Guillaume, France

    Alice Gangloff

  8. Department of Digestive Surgery, Rouen University Hospital, Rouen, France

    Lilian Schwarz

  9. Clinical Research Unit, Centre Henri Becquerel, Rouen, France

    Emilie Lévêque

  10. Department of Anatomopathology, Rouen University Hospital, Rouen, France

    Jean-Christophe Sabourin

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  1. Adrien Grancher
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Contributions

AGr FDF DS and VV wrote the manuscript. AGi, TC, EL, AGr, and FDF performed the statistical analysis. KBL, MPG, ALB, VB, CE, AGa, MD, DS and PM collected the data. AGr FDF and VV organized the data and performed the bibliography. LB and SNV performed the ctDNA analysis.

Corresponding author

Correspondence to Frédéric Di Fiore.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

This work combine data from two trials, registered on the clinicaltrials.gov website (No. NCT01212510 and NCT02872779), and approved by an ethic committee (Comité de Protection des Personnes Nord-Ouest 1, Rouen University, 76000 France). Each patient included in these two trials gave written consent. The study was performed in accordance with the Declaration of Helsinki.

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Grancher, A., Beaussire-Trouvay, L., Vernon, V. et al. ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer. Br J Cancer 132, 814–821 (2025). https://doi.org/10.1038/s41416-025-02971-0

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