Abstract P051: The INSPIRE Study (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation): scaling return of genomic results
Authors: Solomon Ilana , Hampel Heather , McDonnell Kevin , Blazer Kathleen , Capasso Alex , Chitre Anuja , Dreike Sandra , Elfarawi Hunaydah , Gima Lauren , Hong Christine , Idos Gregory , King Elisabeth , Manookian Rachelle , Nehoray Bita , Park Wai , Restrepo Michael , Shehayeb Susan , Sobotka Elise , Sturgeon Duveen , Zukin Elyssa , Gray Stacy W. , Gruber Stephen B. 
Published: January 2023

Abstract
Background: To enable genomic care for all City of Hope (COH) patients, we implemented an enterprise-wide Precision Medicine program including 7 of our clinical network sites. Consented patients with and without cancer are eligible to opt into germline testing (155 gene cancer predisposition panel and ACMG 59 Actionable Disorders panel) and paired tumor-normal whole exome/RNA transcriptome sequencing. All assays are CAP-CLIA approved. Results are added to the electronic medical record (EMR). We describe the process of implementation through return of results (RoR). Methods: Potentially eligible patients are identified by their provider or through the EMR. Clinical Research Assistants (n=8, main campus) and Advance Practice Providers (APPs) (n=14 Genetic Counselors or n=1 Genetics Nurse Practitioner) and Licensed Vocational Nurses (n=5, clinical network) consent patients in-person and remotely. Clinical Research Nurses (n=5) or APPs order testing through the EMR, with treating providers copied on somatic results and GCs copied on germline results. All results are systematically reviewed by GCs and/or the weekly COH Precision Oncology Tumor Board (POTB). Results: From July 9, 2020 through August 26, 2022 12,105 patients have been offered participation, with 10,376 (85.7%) enrolling (7,892 original consents/ 2,484 reconsents), 735 (6.1%) declining, 984 (8.1%) deferring, and 10 (.1% ) with other consent statuses. 98.9% (10,259/10,376) opted for cancer predisposition germline testing and 98.5% (10,225/10,376) opted for ACMG Actionable Disorders testing 91.5% (9,497/10,376) patients agreed to future contact about additional research studies. 6,512 somatic tests have been reviewed (representing 6,295 patients) and presented through POTB. Somatic genomic results are uploaded to the EMR via PDF and returned by the treating physician. Germline results are returned through the EPIC genomics module. To scale RoR, patients with negative results, variants of unknown significance, and carriers for recessive conditions are sent letters. Patients with a cancer predisposition P/LP variant are disclosed via phone by a GC and referred to COH Cancer Genomics for counseling whereas patients with P/LP non-cancer ACMG variants are referred for outside genetic counseling through the testing laboratory. To improve efficiency, we do not notify patients of non-actionable variant reclassifications. Conclusion: We outline a new care model for the delivery of germline and somatic genetic testing at scale. High consent and opt-in rates for germline testing demonstrate patient interest and feasibility. Future work is planned to assess the impact of testing on clinical care and outcomes.
Citation Format: Ilana Solomon, Heather Hampel, Kevin McDonnell, Kathleen Blazer, Alex Capasso, Anuja Chitre, Sandra Dreike, Hunaydah Elfarawi, Lauren Gima, Christine Hong, Gregory Idos, Elisabeth King, Rachelle Manookian, Bita Nehoray, Wai Park, Michael Restrepo, Susan Shehayeb, Elise Sobotka, Duveen Sturgeon, Elyssa Zukin, Stacy W. Gray, Stephen B. Gruber. The INSPIRE Study (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation): scaling return of genomic results. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P051.