Oncotarget

Research Papers:

Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor

Caroline Vandeputte, Pashalina Kehagias, Hakim El Housni, Lieveke Ameye, Jean-François Laes, Christine Desmedt, Christos Sotiriou, Amélie Deleporte, Francesco Puleo, Karen Geboes, Thierry Delaunoit, Gauthier Demolin, Marc Peeters, Lionel D’Hondt, Jos Janssens, Javier Carrasco, Raphaël Marechal, Maria Gomez Galdon, Pierre Heimann, Marianne Paesmans, Patrick Flamen, Alain Hendlisz _

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Oncotarget. 2018; 9:17756-17769. https://doi.org/10.18632/oncotarget.24879

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Abstract

Caroline Vandeputte1,*, Pashalina Kehagias1,*, Hakim El Housni2, Lieveke Ameye3, Jean-François Laes4, Christine Desmedt5, Christos Sotiriou5, Amélie Deleporte1, Francesco Puleo1, Karen Geboes6, Thierry Delaunoit7, Gauthier Demolin8, Marc Peeters9, Lionel D’Hondt10, Jos Janssens11, Javier Carrasco12, Raphaël Marechal13, Maria Gomez Galdon14, Pierre Heimann2, Marianne Paesmans3, Patrick Flamen15 and Alain Hendlisz1

1Gastro Intestinal Oncology Unit, Medical Oncology, Institut Jules Bordet, Brussels, Belgium

2Department of Medical Genetics, Hôpital Erasme-ULB, Brussels, Belgium

3Data Centre, Institut Jules Bordet, Brussels, Belgium

4OncoDna, Gosselies, Belgium

5Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

6Service of Digestive Oncology, Universitair Ziekenhuis Gent, Gent, Belgium

7Oncology Department, Hôpital de Jolimont, La Louvière, Belgium

8Gastroenterology Department, Centre Hospitalier Chrétien St-Joseph, Liège, Belgium

9Oncology Department, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium

10Oncology Department, Centre Hospitalier Universitaire, UCL Namur (site de Godinne), Dinant, Belgium

11Department of Gastroenterology, AZ Turnhout, Turnhout, Belgium

12Oncology Department, Grand Hôpital de Charleroi, Charleroi, Belgium

13Department of Gastroenterology, GI Cancer Unit, ULB-Erasme, Brussels, Belgium

14Department of Pathology, Jules Bordet Institute, Free University of Brussels, Brussels, Belgium

15Nucleair Medicine Imaging and Therapy Department, Institut Jules Bordet, Brussels, Belgium

*Shared first authors

Correspondence to:

Alain Hendlisz, email: alain.hendlisz@bordet.be

Keywords: early-response; biomarker; multi-kinase inhibitor; colorectal cancer; ctDNA

Received: June 08, 2017    Accepted: March 01, 2018    Published: April 03, 2018

ABSTRACT

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.


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