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

• Published in: Clinics and research in hepatology and gastroenterology Vol. 48; no. 8; p. 102417
• Main Authors: Kourie, Hampig Raphael, Zouein, Joseph, Zalaquett, Ziad, Chebly, Alain, Nasr, Lewis, Karak, Fadi El, Sadek, Maroun, Safar, Ousama, Fouani, Mouin, Bitar, Nizar, Kachmar, Kamal, Nasr, Fady, Farhat, Fadi, Makarem, Jawad, Kattan, Joseph, Taieb, Julien
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-10-2024
• Subjects: Keyword
• ISSN: 2210-7401; 2210-741X; 2210-741X
• DOI: 10.1016/j.clinre.2024.102417

•Liquid biopsy using Idylla RT-PCR has a sensitivity of 62 % and a specificity of 93 % compared with tissue biopsy for detecting KRAS/NRAS/BRAF mutations in metastatic colorectal cancer.•The most frequent mutations detected by liquid and tissue biopsy are KRAS (41 %), followed by NRAS (4 %) and BRAF (3 %).•No relationship was established between the presence of hepatic metastasis, peritoneal carcinomatosis, pulmonary metastasis or tumor localization and RAS status concordance between liquid and tissue biopsy.
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.
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.
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.
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.
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.