Genetic counseling referrals after next generation sequencing testing.

Abstract

1515 Background: Next generation sequencing (NGS) testing of tumor tissue or blood is performed to identify ‘actionable’ mutations that might guide patient care. NGS testing might incidentally identify germline mutations associated with cancer syndromes. No distinction is made between germline and somatic alterations on NGS reports, thus confirmatory germline testing is required. In this quality improvement (QI) initiative, we evaluated the frequency of referrals to genetic counseling (GC) for patients with potentially heritable germline mutations identified through NGS testing. Methods: We generated a list of high-risk mutations (HRMs) which merit GC referral based on NCCN guidelines. NGS test results for 3,400 consecutive patients with solid tumor malignancies were reviewed by the molecular tumor board from 1/2014-9/2019 and were screened for pathogenic HRMs. Basic demographic, oncologic, and GC data were retrospectively abstracted for each patient. The outcomes of interest were the frequency of HRMs identified through NGS testing, the proportion of patients subsequently referred to GC, and the proportion of patients ultimately diagnosed with a hereditary cancer syndrome. Results: 472 individual patients (14%) had NGS testing with one or more HRM identified; 465 patients were evaluable which corresponded to 519 HRMs that were included in the analysis (Table). Malignancies included were gastrointestinal 199 (42.8%), lung 83 (17.8%), genitourinary/renal 56 (12.0%), breast 49 (10.5%), gynecologic 35 (7.5%), and other 43 (9.2%). 75 (16.1%) patients had germline testing prior to NGS testing. Of those patients without prior germline genetic testing, 62 (15.9%) were referred to GC, and 19 (4.9%) patients were diagnosed with a hereditary cancer syndrome. Conclusions: Tumor NGS testing identifies HRMs that may represent an undiagnosed heritable germline mutation. Providers ordering NGS tests should review results for HRMs, refer to GC when appropriate, and offer confirmatory germline testing for patients and their families. [Table: see text]