Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer.

Autor: Kourie HR; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon. Electronic address: hampig.kourie@usj.edu.lb., Zouein J; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon; Department of Medicine, Duke University Medical Center, Durham, NC, USA., Zalaquett Z; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon., Chebly A; Jacques Loiselet Center for Medical Genetics and Genomics (CGGM), Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; Higher Institute of Public Health, Saint Joseph University, Beirut, Lebanon., Nasr L; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon., Karak FE; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon., Sadek M; Hematology-Oncology Department, Lebanese Hospital Geitaoui, Beirut, Lebanon., Safar O; Dar Al Amal University Hospital, Bekaa, Lebanon., Fouani M; Saint George Hospital, Hadath, Lebanon., Bitar N; Sahel General Hospital, Beirut, Lebanon., Kachmar K; Tebnin Governmental Hospital, Bekaa, Lebanon., Nasr F; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon., Farhat F; Mount Lebanon Hospital, Baabda, Lebanon., Makarem J; Al Jabal Hospital, Chouf, Lebanon., Kattan J; Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon., Taieb J; Hôpital Européen Georges Pompidou, Paris, France.
Jazyk: angličtina
Zdroj: Clinics and research in hepatology and gastroenterology [Clin Res Hepatol Gastroenterol] 2024 Oct; Vol. 48 (8), pp. 102417. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.clinre.2024.102417
Abstrakt: Background: The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples.
Objective: This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy.
Methods: This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy.
Results: 100 patients with mCRC were included in the study. 75 % of patients showed concordant results between liquid biopsy and tissue biopsy, while 25 % had discordant results. Liquid biopsy demonstrated a sensitivity of 62 % and a specificity of 93 %. The accuracy of liquid biopsy was 75 %, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41 %), followed by NRAS (4 %) and BRAF (3 %). Mutations were not detected in 42 % of tissue biopsy samples and 60 % of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods.
Conclusion: Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hampig Raphael Kourie reports financial support was provided by Merck KGaA, Darmstadt, Germany. Hampig Raphael Kourie reports financial support was provided by Biocartis. Hampig Raphael Kourie reports financial support was provided by Saint-Joseph University of Beirut Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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