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.
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.
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Author notes
These authors contributed equally: Adrien Grancher, Ludivine Beaussire-Trouvay.
Authors and Affiliations
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
Normandie Univ, UNIROUEN, Inserm U1245, IRON group, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France
Ludivine Beaussire-Trouvay & Nasrin Vasseur
CHI Elbeuf, Department of Hepatogastroenterology, Elbeuf, France
Valérie Blondin & Caroline Elie
Department of Hepatogastroenterology, Caen University Hospital, Caen, France
Karine Bouhier-Leporrier & Anne-Laure Bignon
Department of Hepatogastroenterology, Francois Baclesse Centre, Caen, France
Marie-Pierre Galais & Aurélie Parzy
Department of Biostatistics, Rouen University Hospital, Rouen, France
Tifenn Clabaut & André Gilibert
Clinique du Cèdre, Bois-Guillaume, France
Alice Gangloff
Department of Digestive Surgery, Rouen University Hospital, Rouen, France
Lilian Schwarz
Clinical Research Unit, Centre Henri Becquerel, Rouen, France
Emilie Lévêque
Department of Anatomopathology, Rouen University Hospital, Rouen, France
Jean-Christophe Sabourin
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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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The authors declare no competing interests.
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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 (2025). https://doi.org/10.1038/s41416-025-02971-0
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Received:23 September 2024
Revised:14 January 2025
Accepted:25 February 2025
Published:15 March 2025
DOI:https://doi.org/10.1038/s41416-025-02971-0
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