Epithelial ovarian cancer (EOC) is the most common histology of ovarian cancer defined as epithelial cancer derived from the ovaries, fallopian tubes, or primary peritoneum. It is the fifth most common cause of cancer-related death in women in the United States. Because of a lack of effective screening and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer consists of a combination of cytoreductive surgery and systemic chemotherapy. Despite the advances with new cytotoxic and targeted therapies, the five-year survival rate for all-stage EOC in the United States is 48.6%. Delivery of up-to-date guideline care and multidisciplinary team efforts are important drivers of overall survival. In this paper, we review our frontline management of EOC that relies on a multi-disciplinary approach drawing on clinical expertise and collaboration combined with community practice and cutting edge clinical and translational research. By optimizing partnerships through team medicine and clinical research, we combine our cancer center clinical expertise, community practice partnership, and clinical and translational research to understand the biology of this deadly disease, advance therapy and connect our patients with the optimal treatment that offers the best possible outcomes.
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.
PURPOSE Although BRCA1/ 2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients ( P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.
Histologic and genetic mutation information from racially and ethnically diverse populations is warranted to better inform future cancer predisposition and promote health equity. A single institutional, retrospective capture of patients with gynecologic conditions and genetic susceptibilities to malignant neoplasms of the breast or ovaries was performed. This was achieved with manual curation of the electronic medical record (EMR) from 2010–2020 with the use of ICD-10 code searches. Among 8983 consecutive women identified with gynecologic conditions, 184 were diagnosed with pathogenic/likely pathogenic (P/LP) germline BRCA (gBRCA) mutations. Median age was 54 (22–90). Mutations included insertion/deletion (majority frameshift, 57.4%), substitution (32.4%), large structural rearrangement (5.4%), and alteration in splice site/intronic sequence (4.7%). A total of 48% were non-Hispanic White, 32% Hispanic or Latino, 13% Asian, 2% Black, and 5% Other. The most common pathology was high grade serous carcinoma (HGSC, 63%), followed by unclassified/high grade carcinoma (13%). Additional multigene panels led to the detection of 23 additional BRCA-positive patients with germline co-mutations and/or variants of uncertain significance in genes functionally involved in DNA repair mechanisms. Hispanic or Latino and Asian individuals comprised 45% of patients with concomitant gynecologic condition and gBRCA positivity in our cohort, confirming that germline mutations are represented across racial and ethnic groups. Insertion/deletion mutations, the majority of which led to a frameshift change, occurred in approximately half of our patient cohort, which may have prognostic implication for therapy resistance. Prospective studies are needed to unravel the significance of germline co-mutations in gynecologic patients.
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