Clinical practice use of liquid biopsy to identify RAS/BRAF mutational status in patients with metastatic colorectal cancer: A single institution experience

Abstract

Introduction: Tumour heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumour tissue. Liquid biopsy allows the detection of DNA alterations in circulating tumour DNA from all metastatic sites and thus overcomes the limitations of single-specimen analysis in terms of tumour heterogeneity. Methods: We assessed 45 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) between July 2018 and February 2019 at the Oncology Unit of Università della Campania “L. Vanvitelli” using Idylla™ Biocartis, a fully automated real-time-PCR-based molecular diagnostic system that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated results from both liquid biopsy and standard tissue-based NGS analysis to clinical characteristics of the patients. Results: The overall agreement with the standard method was 82,2% (37/45 patients). Considering only the tests carried out before the beginning of any systemic treatment the concordance was 84,2% (16/19 patients), while, excluding patients without hepatic metastases, concordance was 92,8% (13/14 patients). Of the 3 cases of discordance at baseline, 2 were RAS/BRAF WTfor liquid biopsy, while resulting KRAS and NRAS mutated on tissue analysis; whereas 1 was NRAS mutated for liquid biopsy, while resulting RAS/BRAF WTon tissue analysis. Notably, the PFS to anti-EGFR therapy in the latter case was 3 months, reflecting a primary resistance to therapy. The other 5 cases of discordance were observed in patients whose tumors were RAS/BRAF WTat baseline on tissue analysis and that resulted KRAS mutated on liquid biopsy after an anti-EGFR treatment, suggesting the emergence of RAS-mutated, resistant cancer cell clones following anti-EGFR monoclonal antibody therapy. Conclusion: Clinical practice testing of RAS/BRAF mutations using the Idylla™ Biocartis liquid biopsy platform is feasible and reliable in mCRC patients. The concordance at baseline is optimal when considering patients with liver metastases. In cases of RAS/BRAF WTanalysis on tumour tissue specimens, liquid biopsy may better predict response to anti-EGFR agents.