A quality improvement initiative to increase genetic testing referrals after identification of hereditable high-risk mutations on next generation sequencing (NGS) (287)

Abstract

<b>Objectives:</b> NGS tumor testing does not currently discern between germline or somatic mutations. Patients with cancer who have an incidentally discovered high-risk mutation(s) (HRMs) may have an associated underlying hereditary cancer syndrome. Referral for genetic counseling and consideration of confirmatory germline testing is recommended. We implemented a quality improvement (QI) initiative to increase referral and testing rates for patients with gynecologic cancer and HRMs identified on NGS tumor testing. Here, we report referral rates before and after this intervention. <b>Methods:</b> All patients with NGS testing results from January 2014 to January 2020 were obtained from an institutional database from our institution's molecular tumor board. Patients with gynecologic cancers and HRMs were identified. HRMs included <i>MLH1, MSH2, MSH6, PMS2, SMAD4, APCI1370K, BMPR1A, EPCAM, BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, NBN, ATM,</i> and <i>CHEK2</i> (Figure 1C<i>).</i> Retrospective chart review was performed for patients with HRMs to determine <i>(1)</i> if the patient had previous germline testing; <i>(2)</i> if no previous testing whether a referral for genetic counseling was recommended; and <i>(3)</i> completion of germline testing occurred. A QI intervention was implemented in February 2020 with weekly centralized review of NGS sequencing results at the Gynecologic Oncology Tumor Board (Figure 1A). Results and recommendations were communicated to the primary gynecologic oncology provider via the electronic medical record. <b>Results:</b> Of 3394 patients with solid tumors who underwent somatic NGS testing during the pre-intervention period, 465 patients (13.7%) had at least one HRM identified, and 66 of these patients (14.2%) were referred for genetic counseling. Prior to our intervention, patients with gynecologic cancer and at least one HRM (<i>n</i>=36) had a higher referral rate for counseling (42.6%) than patients with other solid tumors (14.2%). About 5.5% of patients with gynecologic cancer had previous germline testing prior to NGS testing. Post-intervention, we identified 10/76 (13.2%) patients with gynecologic cancer and an HRM. Of these ten patients, seven had previous germline testing (70% vs 5.5%, p<0.0001), and three patients who did not have previous germline results were referred for counseling, capturing all patients with HRMs (Figure 1B). Results from germline testing are pending. <b>Conclusions:</b> After implementing a QI initiative involving centralized NGS results review and communication of results to the primary gynecologic oncologist, all patients with gynecologic cancer and HRM obtained appropriate referrals to genetic testing. The overall rate of germline genetic testing prior to NGS testing increased significantly in the 2020-2021 time period compared to 2014-2020. Identification of HRMs on NGS warrants referral for genetic counseling and germline testing; our QI initiative ensured adherence to this standard.