Clinical Practice Use of Liquid Biopsy to Identify RAS/BRAF Mutations in Patients with Metastatic Colorectal Cancer (mCRC): A Single Institution Experience.

Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla™ Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-naïve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-naïve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla™ Biocartis platform is feasible and reliable in mCRC patients in clinical practice.

Déclaration de conflit d'intérêts

P.P.V.: consultancy for Biocartis. E.M.: advisory board for Amgen, Bayer, Merck, Roche, Sanofi, Servier and expert opinion for ESMO (European Society of Medical Oncology). T.T.: advisory board for Amgen, Bayer, Merck, Novartis, Roche, Sanofi. F.M.: advisory board for Lilly, MSD. F.D.V.: advisory board for Amgen, Lilly, Roche, Celgene. F.C.: advisory board for Merck, Roche, Amgen, Bayer, Servier, Symphogen,Pfizer and research funding from Roche, Merck, Amgen, Bayer, Ipsen. V.D.F., E.F.G., D.C., C.C., C.B., L.P., M.T., G.A., V.C., A.D.L., V.F., V.M.I., F.M., G.M., S.N., R.F., A.L., M.C. declare no competing conflict of interest regarding the following manuscript. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.