Next-Generation Sequencing Targeted Panel in Routine Care for Metastatic Colon Cancers

SIMPLE SUMMARY: The place of Next-Generation-Sequencing (NGS) targeted panel in routine practice in digestive oncology should be addressed. The aim of our retrospective study was to assess the results and impact of NGS panel for metastatic colorectal cancer (mCRC) patients. In total, 210 patients with mCRC were included. Based on our findings, a major advantage of the NGS panel over single gene techniques is that, beyond the classical hotspots, it allows for an exhaustive search for molecular abnormalities in routinely recommended genes. In addition, routine NGS is a way to detect amplifications associated with resistance to anti-EGFR therapies and low-prevalence mutations in actionable genes, providing patients with the opportunity to access innovative targeted therapies. In conclusion, NGS targeted panel in mCRC is feasible in routine practice. Nevertheless, panels need to be regularly updated and in-depth studies are needed to better analyse the prognostic factors. ABSTRACT: In digestive oncology, the clinical impact of targeted next-generation sequencing (NGS) in routine practice should be addressed. In this work, we studied the impact of a 22-gene NGS amplicon-based panel with Ion Torrent Proton Sequencing, prospectively performed in routine practice. We analyzed the results of extended molecular testing, beyond RAS and BRAF, in metastatic colorectal cancer (mCRC) patients in a single-center, retrospective, observational study of consecutive mCRC patients followed up at the Georges Pompidou European Hospital between January 2016 and December 2018. Overall, 210 patients with mCRC were included. Median follow-up was 25.4 months (IQR: 14.9–39.5). The three most frequently mutated genes were: TP53 (63%), KRAS (41%) and PIK3CA (19%). A positive association was found between overall survival and performance status (PS) ≥ 2 (HR: 4.91 (1.84–13.1); p = 0.001) and differentiation (HR: 4.70 (1.51–14.6); p = 0.007) in multivariate analysis. The NGS panel enabled five patients to access a targeted therapy not currently registered for CRC. In conclusion, targeted NGS panels in mCRC are feasible in routine practice, but need to be regularly updated and in-depth studies are needed to better analyze the prognostic factors.