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

Vitiello PP1, De Falco V2, Giunta EF3, Ciardiello D4, Cardone C5, Vitale P6, Zanaletti N7, Borrelli C8, Poliero L9, Terminiello M10, Arrichiello G11, Caputo V12, Famiglietti V13, Mattera Iacono V14, Marrone F15, Di Liello A16, Martini G17,18, Napolitano S19,20, Caraglia M21, Lombardi A22, Franco R23, De Vita F24, Morgillo F25, Troiani T26, Ciardiello F27, Martinelli E28.

Author information

1: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. pietropaolo.vitiello@gmail.com.
2: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. vincenzodefalc@gmail.com.
3: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. emiliofrancescogiunta@gmail.com.
4: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. davideciardiello@yahoo.it.
5: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. claudia.cardone88@gmail.com.
6: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. vitale.pasquale.89@gmail.com.
7: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. nicolettazanaletti@gmail.com.
8: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. carola.bor@libero.it.
9: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. luca.poliero@libero.it.
10: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. marinella.terminiello@gmail.com.
11: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. gluca.arrichiello@gmail.com.
12: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. vincenza.caputo.92@gmail.com.
13: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. vincenzo.famiglietti@yahoo.it.
14: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. vmatteraiacono@gmail.com.
15: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. francesca.marrone@email.it.
16: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. dilielloalessandra@gmail.com.
17: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. giulia.mart14@gmail.com.
18: Centro Cellex, Vall D'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain. giulia.mart14@gmail.com.
19: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. stenap@fastwebnet.it.
20: Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. stenap@fastwebnet.it.
21: Department of Experimental Medicine, Università della Campania "Luigi Vanvitelli", 80138 Napoli, Italy. michele.caraglia@unicampania.it.
22: Department of Experimental Medicine, Università della Campania "Luigi Vanvitelli", 80138 Napoli, Italy. angela.lombardi@unicampania.it.
23: Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, Università della Campania "Luigi Vanvitelli", 80138 Napoli, Italy. renato.franco@unicampania.it.
24: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. ferdinando.devita@unicampania.it.
25: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. floriana.morgillo@unicampania.it.
26: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. teresa.troiani@unicampania.it.
27: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy.
28: Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", 80131 Napoli, Italy. erika.martinelli@unicampania.it.

Abstract

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.