Dual germline and somatic testing in women with high-grade epithelial ovarian, tubal, and peritoneal cancer: a prospective systemic quality improvement initiative

Abstract

<h3>Objectives:</h3> Germline and somatic genetic testing can have significant implications for women with ovarian, fallopian tube or peritoneal carcinoma, including therapeutic decisions, prognostic counseling and cascade testing. However, there are obstacles to universal implementation of testing when it is dependent on clinician initiative. Therefore, we implemented a prospective quality improvement (QI) initiative that aimed to assure universal germline and somatic testing in women with newly diagnosed advanced stage, high grade disease. <h3>Methods:</h3> A systematic program was established to ensure that all patients with newly diagnosed, advanced stage ovarian, tubal or peritoneal carcinoma who were scheduled for formal genetics consultation underwent dual Myriad MyRisk multigene germline testing and Myriad MyChoice somatic testing for <i>BRCA1/2</i> mutations and genomic instability. The primary objective was to compare the frequency of germline and somatic testing between the pre-initiative (1/1/2015 - 3/31/2018) and post-initiative (4/1/2018- 7/1/2020) periods. Secondary objectives included comparison of time intervals between diagnosis and testing, incidence of ‘insufficient samples' for somatic testing, and clinical utilization of results. Descriptive statistics were used. Paired Student's T test was used to compare continuous variables; chi-square test was used to compare discrete variables. <h3>Results:</h3> There were 209 women in this study: 122 in the pre-intervention cohort and 87 in the post-intervention cohort. Among women in the pre-intervention group, 90 (74%) and 48 (39%) underwent germline and somatic testing, respectively, compared to 77 (89%) and 66 (76%) in the post-intervention cohort. Implementation of a systemic referral system with dual testing doubled the rate of somatic testing (p<0.01). Among all women who underwent germline testing, 10.1% had a g<i>BRCA1</i> mutation and 2.4% a g<i>BRCA2</i> mutation. Of all who underwent somatic testing, 6.2% had a s<i>BRCA1</i> mutation and 4.3% a s<i>BRCA2</i> mutation. All germline <i>BRCA1</i> and <i>BRCA2</i> mutations were also identified on somatic testing. There were 20 cases (9.5%) with negative germline multigene panels also lacking somatic <i>BRCA1/2</i> mutations that were found to have genomic instability. Among the 114 patients who received somatic testing, 29 (25.4%) had biomarkers (<i>BRCA1/2</i> mutation or genomic instability) predictive of major benefit from poly-ADP ribose polymerase inhibitors (PARPi) despite lacking germline mutations. Median time from diagnosis to germline testing decreased to 3.7 months in the post-intervention compared to 6.2 months in the pre-intervention cohort. <h3>Conclusions:</h3> Systematic referral for both germline and somatic genetic testing significantly increased the frequency of somatic testing, and results were obtained sooner in patients with advanced ovarian, fallopian tube and peritoneal cancers. In patients who underwent dual testing and lacked germline mutations, 25% had either a somatic <i>BRCA1</i> or <i>BRCA2</i> mutation or genomic instability that could help direct therapy. Since both germline and somatic mutations and genomic instability status increasingly play a role in directing therapy, earlier and consistent testing is of the upmost importance.