Mutational analysis of >14,000 NGS tests from community oncology practices: The Sarah Cannon molecular landscape.

26 Background: Utilization of NGS-based testing for patients in community oncology settings continues to grow. A comprehensive analysis of the molecular landscape of > 14,000 patients with commercial tissue-based and plasma-based NGS (tbNGS and pbNGS) testing from Sarah Cannon’s (SC) network of community oncologists between 2012 and 2018 was performed. These data aid clinical trial design/feasibility and identify rare and actionable mutations in the community oncology setting. Methods: Medical Oncologists in the SC network ordered NGS-based molecular profiling for their patients as standard of care. Data from multiple commercial vendors starting in 2012 were harmonized and analyzed. Results: On average, tbNGS (n = 8938) and pbNGS (n = 5419) tests revealed 14 and 4 mutations/sample, respectively. The top 10 mutated genes from both tbNGS and pbNGS - tests are in the table. The most predominant mutation-types detected were SNVs in both tbNGS and pbNGS tests, and gene amplifications were detected in ~40% of tbNGS and ~22% of pbNGS tests. MET amplifications (range: 2 - 40 copies (pbNGS) and 6 - 82 copies (tbNGS)) and ERBB2 amplifications (range: 2.1 - 90.2 copies (pbNGS) and 4 - 293 copies (tbNGS)) were detected in 1.6% (MET-tbNGS) and 4.6% (MET-pbNGS) and 4.2% (ERBB2-tbNGS) and 2.69% (ERBB2-pbNGS) of patients, respectively, and informed clinical trial enrollment. Of the fusions detected, 28 NTRK rearrangements were detected (NTRK1 – 16, NTRK2 – 5, NTRK3 – 7) by tissue-based testing and 3 (NTRK1) fusions were detected by plasma-based tests. Conclusions: These data describe the mutational landscape of NGS tests ordered within community oncology practices. SC’s data infrastructure links NGS-based testing data and clinical data to support real world evidence research, and highlights the need for healthcare IT systems to marry clinical and genomic data for clinical decision support and clinical research. [Table: see text]