Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer
Hampig Raphael Kourie1, Joseph Zouein2, Ziad Zalaquett1
1Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon.
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.
Insights
Liquid biopsy shows high specificity but lower sensitivity for detecting RAS/BRAF mutations in metastatic colorectal cancer (mCRC) patients. This less invasive method is a promising alternative to tissue biopsy, despite some discordant results.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- RAS wild type status in metastatic colorectal cancer (mCRC) predicts response to anti-EGFR therapy.
- Tissue biopsy is the current standard for RAS mutational analysis.
Purpose of the Study:
- To evaluate liquid biopsy as a less invasive alternative to tissue biopsy for KRAS/NRAS and BRAF mutation detection in mCRC.
- To determine the concordance between liquid and tissue biopsy results.
Main Methods:
- Phase IV, observational study involving 100 mCRC patients.
- Comparison of RAS/BRAF status using liquid and tissue biopsies with PCR-based devices.
- Primary endpoint: comparison of RAS status between liquid and tissue biopsies.
Main Results:
- 75% concordance between liquid and tissue biopsies.
- Liquid biopsy sensitivity: 62%, specificity: 93%, accuracy: 75%.
- KRAS mutations were most frequent (41%) in concordant cases.
Conclusions:
- Liquid biopsy offers high specificity for detecting mCRC mutations but has lower sensitivity.
- Despite discordance, liquid biopsy is a promising, non-invasive alternative due to its potential for multiple sampling and better tumor heterogeneity representation.
