Analysis of clinical and research implications of expanding next-generation sequencing (NGS) libraries in the treatment options of gastrointestinal cancers in a large cancer center.

Abstract

774 Background: The use of next-generation sequencing (NGS) in clinical practice has increased the therapeutic options for many cancers. Multiple NGS assays are now commercially used. The genomic libraries used by these assays are continuously being expanded, resulting in increased detections of genomic alterations (GAs) leading to potential new treatments. The aim of this study was to identify the clinical and research implications of a database expansion in the detection of GAs in patients with gastrointestinal cancers (GIC). Methods: We retrospectively analyzed 83 consecutive patients with GIC that had NGS at the John Theurer Cancer Center between 01/2014 and 08/2016. GAs were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of genomic-directed therapies and number of clinical trials were reviewed. Results: Period 1 (P1) comprised 01/2014-09/2014, period 2 (P2) comprised 10/2014-08/2016. The NGS assay interrogated 236 genes and introns of 19 genes during P1, and was expanded to 315 genes and introns of 28 genes during P2. The 21 samples analyzed during P1 harbored a total of 82 GAs with an average of 3.9 GAs/sample (range 1-7). The 62 samples analyzed during P2 harbored a total of 342 GAs with an average of 5.5 GAs/sample (range 1-20); representing an increase of 42% in GAs from P1 to P2. 41 GAs in 29 genes were detected in P2 that were not interrogated during P1. The average of genomic-directed therapies with potential clinical benefit increased from 1.8 during P1 vs 2.6 during P2 (44.4% increase in potential therapies). Based on new genomic findings, more clinical trials were made available during P2; an average of 8 vs 4 clinical trials (100% increase in available clinical trials). Conclusions: Periodical updates on NGS and the expansion of genomic libraries increase the detection of GAs, potential new genomic-directed therapies and available clinical trials. Continued expansions of NGS are needed to improve genomic characterization, and increase in the personalized therapeutic options for our patients with GIC.