Background: Reduced access to treatment advances in rural populations contributes to increased cancer mortality. Rural Appalachian Kentucky is a geographically isolated population with a unique carcinogen exposure and a low frequency guideline-recommended germline testing. To improve testing rates, a return of germline results program for patients enrolled in the Total Cancer Care (TCC) protocol at Markey Cancer Center (MCC) was initiated. Methods: Pre-intervention testing rates were obtained from the electronic health record. Patient and physician focus groups were conducted to assess barriers to germline testing. Whole exome germline data from TCC patients enrolled in the Avatar subset is analyzed using standard bioinformatics pipeline for known, clinically significant mutations in the 59 American College of Medical Genetics (ACMG) genes where return of incidental germline findings is recommended and 21 pharmacogenetic genes. Results are reviewed by our Molecular Tumor Board and a recommendation for confirmatory clinical testing, if needed, is made to the treating physician. Results: Baseline rates of guideline recommended germline testing at MCC in 2018 was 20% of ovarian, 15% of breast, 9% of colon, 3% of pancreas and no metastatic prostate patients. Testing was infrequent in rural communities. Almost all patients who had testing recommended by their physician, had testing performed. Unaffected family members were also rarely tested. Physician focus groups at MCC identified lack of time and low perceived value of the testing as barriers. Rural physicians also identified lack of access to genetic counselors. Patient focus groups in the Appalachian region demonstrated poor quality internet and low knowledge and self- efficacy as major barriers to patients discussing genetic testing with family members. To overcome patient barriers, a preloaded audio card was developed to facilitate discussion with family members. The preloaded audio card was tested in a rural Appalachian community, demonstrating significantly improved knowledge and self-efficacy. To overcome physician barriers, a genetic counselor telemedicine clinic and standing order were initiated. To improve physician perception of test value, the ORIEN return of germline results project was initiated. Of the more than 2000 patients enrolled on TCC at MCC, approximately 40% are from Appalachia, 173 have appropriate consent and specimen availability for germline sequencing and 5 have had results returned. Data describing the first 3 months of this initiative, including frequency of mutations in patients and unaffected family members and acceptance of genetic counselor referrals by physicians, patients and family members will be presented. Conclusion: Rural Appalachian communities identified significant barriers to guideline recommended germline testing, however, ORIEN and the TCC protocol are novel methods to reduce these barriers and improve the rates of testing in both patients and their family members.

Citation Format: Jill Kolesar, Micheal Cavnar, Rachel Miller, Justine Pickarski, Shulin Zhang, Kannabiran Nandakumar, Marissa Schuh, Elizabeth Belcher, Eric Durbin, Ming Poi, Fred Ueland, Isaac Hands, Therese Bocklage, JC Jeong, Susanne Arnold, Mark Evers. Improving cancer germline testing in rural Appalachian populations with ORIEN [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A001.