Clinical implications of next-generation sequencing in the treatment of brain cancer at a large academic institution.

Abstract

e13521 Background: The use of next-generation sequencing (NGS) in clinical practice has increased the treatment (tx) options for cancer patients (pts). The expansion of genomic libraries used by NGS databases has resulted in increased identification of targetable genomic alterations (GAs). The aim of this study was to identify the clinical implications of genomic library expansion in the detection of GAs in pts with brain cancer at a large academic institution. Methods: We retrospectively analyzed 71 consecutive pts with brain cancer at the John Theurer Cancer Center that had NGS performed between 02/2014 and 09/2016. GAs were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number (n) of available genomic-directed tx and n of clinical trials were reviewed. The NGS assay interrogated 236 genes and introns of 19 genes until 09/2014, and subsequently was expanded to include 315 genes and introns of 28 genes. We compared median survival, n of GAs found, n of available trials, and n of tx available in pts who received NGS until 09/2014 (G1, n = 33) with pts who received NGS after 9/2014 (G2, n = 38). Results: Median survival was 30 months (range 19.9-40.1), median age was 62 years (range 26-82), the median n of GAs/sample was 5 (range 1-11). There was a significant positive correlation between n of GAs/sample and n of available trials and tx (r = .5, p = .00 and r = .3, p = .00, respectively). There was a negative correlation between survival and n of GAs (r = -.3, p = .02). G1 harbored 142 GAs with a median n of 4 GAs/sample (range 1-10), while G2 harbored 170 GAs with a median n of 5.5 GAs/sample (range 0-11). There was an absolute increase of 19.7% in GAs in G2 compared to G1. There was no difference in median overall survival. Conclusions: The expansion of genomic libraries increased the detection of GAs, and was positively correlated with the n of tx and clinical trials available for brain cancer pts. Survival was not affected by the expansion of the genomic library, but higher n of GAs was correlated with shorter survival. Expansions of NGS databases lead to increased n of potential tx options for brain cancer pts. Further studies are needed to investigate the impact of NGS targeted tx on survival.