Outcomes after targeted treatment based on somatic tumor genetic testing for women with gynecologic cancers.

OBJECTIVE: Molecular tumor profiling and next-generation sequencing are being increasingly utilized, but there are limited data on the therapeutic implications and potential benefits of targeted treatments. We aim to characterize gynecologic oncology patients referred for somatic tumor genetic mutation testing and assess survival outcomes, efficacy, and toxicities of those receiving targeted therapy. METHODS: We conducted a retrospective chart review of gynecologic oncology patients referred for somatic tumor testing by next generation sequencing between 1/1/2012-8/23/2019. The primary objective was to compare overall and progression free survival between those treated with targeted therapy (group 1) versus traditional treatment (group 2). RESULTS: Most patients (70%) had additional treatment options available based on actionable mutations. The median number of somatic mutations identified was 5 (range 0-53). Patients in group 1 had more actionable somatic mutations (median 2 versus 0, p < 0.001). There was no difference in OS (median 64 versus 76 months, p = 0.97) or PFS (median 2 versus 8 months, p = 0.05) between the groups. While fewer patients in group 1 experienced neuropathy (0 versus 5, p = 0.02), grade I/II thrombocytopenia (7 versus 13, p = 0.03), grade III/IV thrombocytopenia (0 versus 4, p = 0.02), and grade III/IV neutropenia (1 versus 9, p = 0.002), all other non-hematologic toxicities were similar in the two groups. CONCLUSIONS: Most gynecologic cancer patients have actionable mutations and may benefit from a personalized targeted therapy treatment plan. Next generation sequencing can be used to identify clinically actionable mutations in gynecologic cancers and guide the selection of treatments, thereby expanding treatment options without worsening survival or toxicity.

Primary care physician experiences utilizing a family health history tool with electronic health record-integrated clinical decision support: an implementation process assessment.

Family health history (FHH) screening plays a key role in disease risk identification and tailored disease prevention strategies. Primary care physicians (PCPs) are in a frontline position to provide personalized medicine recommendations identified through FHH screening; however, adoption of FHH screening tools has been slow and inconsistent in practice. Information is also lacking on PCP facilitators and barriers of utilizing family history tools with clinical decision support (CDS) embedded in the electronic health record (EHR). This study reports on PCPs' initial experiences with the Genetic and Wellness Assessment (GWA), a patient-administered FHH screening tool utilizing the EHR and CDS. Semi-structured interviews were conducted with 24 PCPs who use the GWA in a network of community-based practices. Four main themes regarding GWA implementation emerged: benefits to clinical care, challenges in practice, CDS-specific issues, and physician-recommended improvements. Sub-themes included value in improving patient access to genetic services, inadequate time to discuss GWA recommendations, lack of patient follow-through with recommendations, and alert fatigue. While PCPs valued the GWA's clinical utility, a number of challenges were identified in the administration and use of the GWA in practice. Based on participants' recommendations, iterative changes have been made to the GWA and workflow to increase efficiency, upgrade the CDS process, and provide additional education to PCPs and patients. Future studies are needed to assess a diverse sample of physicians' and patients' perspectives on the utility of FHH screening utilizing EHR-based genomics recommendations.

Patient perspectives following pharmacogenomics results disclosure in an integrated health system.

AIM: To assess patient perceptions and utilization of pharmacogenomics (PGx) testing in an integrated community health system. METHODS: Fifty-seven patients completed an online survey assessing their experiences with PGx testing offered through two methods: a designated PGx clinic or direct access in-home testing. RESULTS: The majority of participants perceived PGx testing as helpful in their healthcare and reported understanding their results. Some had concerns about privacy and discrimination; most lacked familiarity with the Genetic Information Nondiscrimination Act. There were no significant differences in views between participants tested through either model. CONCLUSION: Participants reported value in both methods of PGx testing. Patient experiences, understanding and result utilization will play an important role in informing future development and implementation of PGx programs.

Primary care physician experiences with integrated pharmacogenomic testing in a community health system.

AIM: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system. METHODS: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews. RESULTS: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs. CONCLUSION: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.

Implementation of a multidisciplinary pharmacogenomics clinic in a community health system.

PURPOSE: The development and implementation of a multidisciplinary pharmacogenomics clinic within the framework of an established community-based medical genetics program are described. SUMMARY: Pharmacogenomics is an important component of precision medicine that holds considerable promise for pharmacotherapy optimization. As part of the development of a health system-wide integrated pharmacogenomics program, in early 2015 Northshore University Health-System established a pharmacogenomics clinic run by a multidisciplinary team including a medical geneticist, a pharmacist, a nurse practitioner, and genetic counselors. The team identified five key program elements: (1) a billable-service provider, (2) a process for documentation of relevant medication and family histories, (3) personnel with the knowledge required to interpret pharmacogenomic results, (4) personnel to discuss risks, benefits, and limitations of pharmacogenomic testing, and (5) a mechanism for reporting results. The most important program component is expert interpretation of genetic test results to provide clinically useful information; pharmacists are well positioned to provide that expertise. At the Northshore University HealthSystem pharmacogenomics clinic, patient encounters typically entail two one-hour visits and follow a standardized workflow. At the first visit, pharmacogenomics-focused medication and family histories are obtained, risks and benefits of genetic testing are explained, and a test sample is collected; at the second visit, test results are provided along with evidence-based pharmacotherapy recommendations. CONCLUSION: A multidisciplinary clinic providing genotyping and related services can facilitate the integration of pharmacogenomics into clinical care and meet the needs of early adopters of precision medicine.