The devil you know: A population-level analysis of tumor-based next-generation sequencing of high-grade epithelial ovarian cancer (151)

Abstract

<b>Objectives:</b> Clinical use of tumor-based next-generation sequencing (tbNGS) is expanding, but the indications and implications remain vague. We aimed to assess the clinical relevance of tbNGS data in a large cohort of patients with high-grade epithelial ovarian cancer. <b>Methods:</b> Electronic medical records (both internal notes and external scanned documents) of 905 patients with high-grade serous or endometrioid ovarian cancer were queried for tbNGS data using optical character recognition (OCR) and natural language processing (NLP) technologies. Identified results and clinical-demographic information were entered into an institutional database. Data were analyzed with descriptive statistics and log-rank tests comparing selected genetic alterations to progression-free survival (PFS). <b>Results:</b> Three hundred and twelve (34.4%) patients had their tbNGS results identified. Tests used had variable breadth, ranging from 46 genes to whole-exome sequencing. The most common was an institutional panel that evaluated 146 genes. Nearly all (99.7%) patients had their genomic alterations (mutations or copy number variations) identified. On average, each tumor had 2.38 (±2.46) aberrations. Two hundred and fifty-two (80.8%) patients had actionable alterations, defined as relaying eligibility for targeted treatment or clinical trial, according to the Precision Oncology Decision Support System (PODSS) database. Twenty-seven (10.7% of those with actionable abnormalities) enrolled in relevant clinical trials. In total, 630 mutations were detected in the population, with half of these (58.6%) considered actionable. The most common type of abnormality encountered was missense substitution (52.9%), followed by amplification (14.7%) and a frameshift mutation (9.72%). The most frequently mutated genes were <i>TP53</i> (93.0%), <i>PIK3CA</i> (9.35%), <i>BRCA1/2</i> (8.30%), <i>NF1</i> (4.90%), and <i>KRAS</i> (4.52%). Among these, only <i>BRCA1/2</i> was associated with a significant improvement in PFS (20.1 vs 14.1 months, p=0.046). <i>CCNE1</i> amplification, the most prevalent copy number variant, was present in 9.4% of those tested. Specific mutation types or copy number variations were not correlated with PFS. <b>Conclusions:</b> Clinical use of tbNGS is prevalent in ovarian cancer. Of patients undergoing tbNGS at our institution, four out of five gained the opportunity for an FDA-approved treatment or genotypically relevant clinical trial. Description of population-level tumor genomics could help identify therapeutic targets and guide the development of clinical decision support tools.