Testing In Ovarian Cancer Patients Research Articles

Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients.

Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

Difficulties and inequities in access to homologous recombination deficiency testing in ovarian cancer patients

Difficulties and inequities in access to homologous recombination deficiency testing in ovarian cancer patients

Development of ovarian cancer biomarker electronic clinical quality measure: Lessons learned.

420 Background: ASCO received funding from the Gordon & Betty Moore Foundation’s Diagnostic Excellence Initiative to develop and test a biomarker electronic Clinical Quality Measure (eCQM) in ovarian cancer. Methods: Working collaboratively with a Technical Expert Panel (TEP), ASCO staff explored the development of an eCQM, Appropriate Germline Testing for Ovarian Cancer Patients to assess the rates of testing for BRCA1/2 germline mutations in adult ovarian cancer patients. The measure underwent clinical workflow analysis; feasibility; face, empiric, and data element validity; and signal-to-noise reliability testing. Results: Feasibility testing indicated an inability to reliably differentiate between germline and somatic BRCA1/2 testing in an eCQM specification due to both a lack of specificity in existing codes, and inconsistent use of appropriate codes to reflect germline testing. Among the 32 individual clinicians across 12 testing sites, overall measure performance ranged from 6.25 to 100 percent, with a 52.3 percent mean performance score (95 percent CI [39.9, 64.7]), indicating a performance gap and variation in care in germline testing among the ovarian cancer patient population. Conclusions: This measure development effort illustrated a scenario where medical practice has advanced beyond current data availability and coding specificity in a way that impacts stakeholder ability to reliably assess the delivery of personalized cancer care and minimize the burden of that measurement. While we concluded the implementation of an eCQM to assess rates of germline testing in ovarian cancer patients was infeasible and premature, ASCO continues to advance the registry-based Clinical Quality Measure (CQM) version of the measure, as testing indicated the CQM is reliable, valid, and reflected continued variation in care. ASCO supports efforts to advance towards robust, meaningful digital quality measures using things like Fast Healthcare Interoperability Resources (FHIR) and Minimal Common Data Elements (mCODE) initiatives, which will enable more standardized data capture and increase the availability and utility of granular data needed for assessing quality cancer care. ASCO also seeks to expand the denominator of this measure to include additional cancer types where germline BRCA1/2 testing is appropriate. Denominator expansion will not only significantly broaden the impact of the measure, but also increase longevity of the measure’s potential use in cross-cutting reporting initiatives such as the Merit-based Incentive Payment System (MIPS) Value Pathways (MVPs).

Information practices around genetic testing for ovarian cancer patients

AbstractKnowledge of ovarian cancer patients' information practices around cancer genetic testing (GT) is needed to inform interventions that promote patient access to GT‐related information. We interviewed 21 ovarian cancer patients and survivors who had GT as part of the treatment process and analyzed the transcripts using the qualitative content analysis method. We found that patients' information practices, manifested in their information‐seeking mode, information sources utilized, information assessment, and information use, showed three distinct styles: passive, semi‐active, and active. Patients with the passive style primarily received information from clinical sources, encountered information, or delegated information‐seeking to family members; they were not inclined to assess information themselves and seldom used it to learn or influence others. Women with semi‐active and active styles adopted more active information‐seeking modes to approach information, utilized information sources beyond clinical settings, attempted to assess the information found, and actively used it to learn, educate others, or advocate GT to family and friends. Guided by the social ecological model, we found multiple levels of influences, including personal, interpersonal, organizational, community, and societal, acting as motivators or barriers to patients' information practice. Based on these findings, we discussed strategies to promote patient access to GT‐related information.

Homologous Recombination Deficiency Score Determined by Genomic Instability in a Romanian Cohort.

The Homologous Recombination Deficiency (HRD) Score, determined by evaluating genomic instability through the assessment of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), serves as a crucial biomarker for identifying patients who might benefit from targeted therapies, such as PARP inhibitors (PARPi). This study aimed to investigate the efficacy of HRD testing in high-grade serous ovarian carcinoma, tubal, and peritoneal cancer patients who are negative for somatic BRCA1 and BRCA2 mutations and to evaluate the impact of HRD status on Bevacizumab and PARPi therapy response. A cohort of 100 Romanian female patients, aged 42-77, was initially selected. Among them, 30 patients had unsuitable samples for HRD testing due to insufficient tumor content or DNA integrity. Using the OncoScan C.N.V. platform, HRD testing was successfully performed on the remaining 70 patients, with 20 testing negative and 50 testing positive for HRD. Among the HRD-positive patients, 35 were eligible for and benefited from PARPi maintenance therapy, resulting in a median progression-free survival (PFS) increase from 4 months to 8.2 months. Our findings support the importance of HRD testing in ovarian cancer patients, demonstrating the potential therapeutic advantage of PARPi therapy in HRD-positive patients without somatic BRCA1/2 mutations.

Testing of newly diagnosed advanced high grade ovarian cancer (OC) patients with the Myriad Genetics MyChoice CDx Plus next generation sequencing-based in vitro diagnostic test emphasizes the need for public insurance coverage of genetic testing: Results of a national program by the Hellenic Society of Medical Oncology (HeSMO).

e18520 Background: Homologous Recombination deficiency (HRD) represents a distinct entity in OC. Clinical data suggest that treatment selection can be based on both BRCA1/2 mutations and bearing Genomic Instability Status (GIS). Testing for GIS is critical in order to expand patients’ pool for targeted treatment. Myriad my Choice, is currently the only FDA approved test that can detect HRD by assessing BRCA1/BRCA2 mutation and GIS status in OC tumor specimens using 3 biomarkers: loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions. To address this need, HeSMO has initiated a national program to provide access to myChoice to newly diagnosed patients with high grade stage III/IV OC. Methods: Patients with newly diagnosed stage III/IV high grade OC were eligible to participate in this program. The specific performance characteristics of myChoice CDx assay were determined on FFPE tumor samples by the evaluation of a range of representative tumor BRCA1 and BRCA2 sequence variants (e.g. single nucleotide variants, insertions or deletions and variants in homopolymers), Large Rearrangements (e.g. deletions and duplications affecting single and multiple exons) and a representative range of GIS. The overall results are composed of two major components: GIS Status (positive or negative) and tumor (t) BRCA1/2 Status (positive or negative). The combined results form the basis of the overall interpretation of the myChoice CDx Myriad HRD Status. Results: From December 2020 to January 2022, 454 patients from all over the country were tested within this program. 220 patients (48.46%) had a positive GIS report and 179 (39.43%) had a negative one. Among GIS positive cases, 122 patients were tBRCAwt (26.87%) 78 patients were tBRCA mutated (17.18%) and 10 patients had suspected deleterious BRCA1/2 mutations (2.20%). Inconclusive was the report in 38 specimens (8.37%) and myChoice Lab failed to complete the analysis in 15 cases (3.30%). Furthermore, mutations were also detected in a number of other genes, including but not limited to, ATM, BRIP1, PALB2, RAD51C, RAD51D, FANCL, CHEK2. Conclusions: In our series, 48.46% of the patients with high grade OC tested as BRCA1/2 and/or GIS positive, in accordance with published data, underlying the clinical need to implement GIS testing in OC patients’ molecular evaluation. Apart from the significant implications for treatment possibilities in an expanded patients’ population, these results are important for cancer prevention. We strongly believe that our results will strengthen our efforts for reimbursement of such testing in high grade OC patients, and will serve as a roadmap for the establishment of local HRD testing solutions.

Healthcare professionals’ perspectives on implementation of universal tumor DNA testing in ovarian cancer patients: multidisciplinary focus groups

Universal tumor DNA testing in epithelial ovarian cancer patients can function not only as an efficient prescreen for hereditary cancer testing, but may also guide treatment choices. This innovation, introduced as Tumor-First workflow, offers great opportunities, but ensuring optimal multidisciplinary collaboration is a challenge. We investigated factors that were relevant and important for large-scale implementation. In three multidisciplinary online focus groups, healthcare professionals (gynecologic oncologists, pathologists, clinical geneticists, and clinical laboratory specialists) were interviewed on factors critical for the implementation of the Tumor-First workflow. Recordings were transcribed for analysis in Atlas.ti according to the framework of Flottorp that categorizes seven implementation domains. Healthcare professionals from all disciplines endorse implementation of the Tumor-First workflow, but more detailed standardization and advice regarding the logistics of the workflow were needed. Healthcare professionals explored ways to stay informed about the different phases of the workflow and the results. They emphasized the importance of including all epithelial ovarian cancer patients in the workflow and monitoring this inclusion. Overall, healthcare professionals would appreciate supporting material for the implementation of the Tumor-First workflow in the daily work routine. Focus group discussions have revealed factors for developing a tailored implementation strategy for the Tumor-First workflow in order to optimize care for epithelial ovarian cancer patients. Future innovations affecting multidisciplinary oncology teams including clinical geneticists can benefit from the lessons learned.

A systematic review and meta-analysis of genetic assessment for women with ovarian cancer: how can we do better?

<h3>Objectives:</h3> Despite clear consensus guidelines recommending universal germline genetic testing in ovarian cancer patients and a growing appreciation of the significant health implications for patients and their relatives, fewer than 50% of women with ovarian cancer undergo genetic testing. We aim to use systematic review and meta-analysis to assess the status of genetic testing in ovarian cancer and identify strategies that can improve uptake of genetic assessment in this high-risk population. <h3>Methods:</h3> A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for studies reporting on genetic testing in ovarian cancer without date restriction was performed. Random effects pooled proportions were calculated using the logit transformation and 95% confidence intervals for individual study proportions were calculated using the Clopper-Pearson exact method. <h3>Results:</h3> The comprehensive search produced 3026 studies, among which 38 met inclusion criteria. Among studies listing mean age of diagnosis, stage, and histology data, the median of the mean age of diagnoses across the studies was 60.5 years. The median proportion of patients with early stage (I/II) ovarian cancer was 22.8%, late stage (III/IV) 70%, and unknown stage 3.6%. The median proportion of patients with serous histology was 74.6%, endometrioid 8.6%, mucinous 6%, clear cell 7%, mixed 3.6%, carcinosarcoma 3.4%, adenocarcinoma 5.8%, and other/unknown histology 7.9%. Twenty-one papers described rates of referral to genetic counseling and found, among 9,629 women, a referral rate of 56% [CI 32-78%]. Twenty-three papers described genetic testing uptake without a specified intervention and found, among 16,412 women, 34% [CI 23-47%] underwent genetic testing (Figure 1). For patients completing genetic testing, 27% [CI 22-32%] had a pathogenic mutation and 7% [CI 3-16%] a variant of uncertain significance. The most successful strategy aimed at improving rates of genetic testing was ‘mainstreaming,' the process of providing counseling and testing in the oncology clinic by trained non-genetics specialists. With mainstreaming, 99% [CI 86-100%] of patients completed genetic testing. Other strategies described in the literature included the use of telemedicine for genetic services (75% underwent genetic testing [CI 43-93%]), embedding a genetic counselor in the clinic (67% [CI 32-90%]), reflex somatic tumor <i>BRCA1/2</i> testing to triage to germline testing (64% [17-94%]), practice recommendation for universal testing of all ovarian cancer patients (42% [CI 15-74%]), and incorporating dedicated referral forms into practice (26% [CI 10-53%]). <h3>Conclusions:</h3> Identifying causative germline mutations in ovarian cancer can impact treatment decisions, inform risk of other malignancies and guide disease prevention and early detection in at-risk relatives. Rates of both referral to genetic counseling and testing remain low, 56% and 34% respectively, despite broad recommendations for universal testing. Mainstreaming, use of telemedicine, embedding genetic counselors in the clinic, and triage via reflex somatic <i>BRCA1/2</i> assessment are all strategies demonstrating success in this patient population and should be considered for those providing care to women with ovarian cancer.

Innovation in germline and somatic tumor testing pathways for ovarian cancer patients

<h3>Objectives:</h3> New approvals for upfront maintenance therapy with parp inhibitors in ovarian cancer now indicate a need for germline genetic testing and potentially somatic testing including homologous repair deficiency (HRD) within several months of diagnosis. However, national rates of germline testing are approximately 30%1 despite being recommended for all patients. Current practice now indicates that it is even more important to obtain results quicker and more efficiently at the time of a new diagnosis of ovarian cancer. We sought to apply novel healthcare innovation techniques to this problem space to improve rates of germline and somatic tumor testing in ovarian cancer patients. <h3>Methods:</h3> A total of 4 pilots ranging from "low to high touch" were performed in an experimental rapid cycle model, each lasting approximately 2-3 weeks. In Pilot 1, providers were "nudged" via email, text or electronic medical record (EMR) alert as per their preference that an upcoming patient was missing either genetic testing or tumor testing (HRD or somatic testing). In Pilot 2, choice architecture was used to pend orders for genetics consultation into the upcoming patient encounter in the EMR. In Pilot 3, a "Concierge Approach" was applied to capture patients in real time who were approached in person at the clinic appointment and offered immediate genetic counseling/testing. In Pilot 4, a text messaging platform was used to schedule patients for a counseling/testing appointment. Descriptive statistics were performed. <h3>Results:</h3> Results: Pilot 1: 30 "nudges" were placed but only 50% of encounters documented discussion or ordering of genetic testing. Pilot 2: 75% of pended orders were signed, with 7/12 (58.3%) of patients scheduling a genetic counseling appointment. Pilot 3: 4/6 (66.7%) of patients completed a genetic counseling appointment when offered in real time at the visit and 3/4 (75%) completed testing. Pilot 4: If patients consented to texting for scheduling (50%), the majority of patients were scheduled for counseling or obtained outside testing results (n=8/9, 88.9%). Attendance rates at appointments scheduled via text were 100% (n=5/5). Potential trends in racial disparities were identified within the n=59 patients missing germline or somatic testing, with an increased proportion of Black patients (27.1%) and Asian/Other (13.6%) missing testing, higher than the baseline practice demographics. <h3>Conclusions:</h3> Behavioral economics can be utilized to improve rates of genetic and somatic testing for ovarian cancer patients. Patients typically complete genetic counseling/testing if an appointment is offered in real time. A ‘warm hand-off' is needed for outreach via text for awareness and engagement, however once enrolled, patients participated via text for scheduling and discussion of prior results at high percentages. A ‘concierge approach' is highly successful but not scalable for all but could be used to ‘rescue' missed patients. Potential racial disparities need further exploration to ensure solutions are equitable and applicable to all patients. The growth of precision medicine could benefit from automation and choice architecture utilizing the EMR. This would allow for surfacing of missing clinical data by removing the mental burden of the work required to complete genetic and somatic testing.'

Gene Panel Tumor Testing in Ovarian Cancer Patients Significantly Increases the Yield of Clinically Actionable Germline Variants beyond BRCA1/BRCA2.

Simple SummaryGermline and somatic variant testing of the BRCA1 and BRCA2 genes are important to predict treatment response to PARP inhibitors in ovarian cancer patients. However, germline variants in other genes besides BRCA1 and BRCA2 are associated with ovarian cancer predisposition, which would be missed by a genetic testing aimed only at treatment decision. We aimed to evaluate the yield of clinically actionable germline variants using next-generation sequencing of a customized panel of 10 genes for the analysis of pathology samples of ovarian carcinomas. We identified clinically actionable germline variants in a significantly higher proportion of ovarian cancer patients when compared with genetic testing focused only on BRCA1 and BRCA2. This strategy increases the chance to make available genetic counseling, presymptomatic genetic testing, and gynecological cancer prophylaxis to female relatives who turn out to be healthy carriers of deleterious germline variants. Since the approval of PARP inhibitors for the treatment of high-grade serous ovarian cancer, in addition to cancer risk assessment, BRCA1 and BRCA2 genetic testing also has therapeutic implications (germline and somatic variants) and should be offered to these patients at diagnosis, irrespective of family history. However, variants in other genes besides BRCA1 and BRCA2 are associated with ovarian cancer predisposition, which would be missed by a genetic testing aimed only at indication for PARP inhibitor treatment. In this study, we aimed to evaluate the yield of clinically actionable germline variants using next-generation sequencing of a customized panel of 10 genes for the analysis of formalin-fixed paraffin-embedded samples from 96 ovarian carcinomas, a strategy that allows the detection of both somatic and germline variants in a single test. In addition to 13.7% of deleterious germline BRCA1/BRCA2 carriers, we identified 7.4% additional patients with pathogenic germline variants in other genes predisposing for ovarian cancer, namely RAD51C, RAD51D, and MSH6, representing 35% of all pathogenic germline variants. We conclude that the strategy of reflex gene-panel tumor testing enables the identification of clinically actionable germline variants in a significantly higher proportion of ovarian cancer patients, which may be valuable information in patients with advanced disease that have run out of approved therapeutic options. Furthermore, this approach increases the chance to make available genetic counseling, presymptomatic genetic testing, and gynecological cancer prophylaxis to female relatives who turn out to be healthy carriers of deleterious germline variants.

"I think that a brief conversation from their provider can go a very long way": Patient and provider perspectives on barriers and facilitators of genetic testing after ovarian cancer.

Identify predisposing, enabling, and reinforcing factors impacting genetic counseling/testing among ovarian cancer patients guided by Green and Kreuter's PRECEDE-PROCEED model. Gynecologic oncology providers (N = 4), genetic counselors (N = 4), and ovarian cancer patients (N = 9) completed semi-structured qualitative interviews exploring participants' knowledge of and experiences with genetic counseling/testing. Interviews were audio recorded, transcribed verbatim, and analyzed using inductive content analysis by two independent raters. Thematic analysis identified predisposing, enabling, and reinforcing factors impacting referral for and uptake of genetic counseling/testing. Predisposing factors included participant's knowledge, beliefs, and attitudes related to genetic counseling/testing. Both patients and providers also cited that insurance coverage and out-of-pocket cost are major concerns for ovarian cancer patients considering genetic testing. Finally, both patients and providers emphasized that genetic counseling/testing would provide additional information to an ovarian cancer patient. While providers emphasized that genetic testing results were useful for informing a patient's personal treatment plan, patients emphasized that this knowledge would be beneficial for their family members. Barriers to genetic testing for ovarian cancer patients exist at multiple levels, including the patient (e.g., knowledge, attitudes), the provider (e.g., workload, availability of services), the institution (e.g., difficulty with referrals/scheduling), and the healthcare system (e.g., insurance/cost). Interventions aiming to increase genetic testing among ovarian cancer patients will likely need to target multiple levels of influence. Future quantitative studies are needed to replicate these results. This line of work will inform specific multilevel intervention strategies that are adaptable to different practice settings, ultimately improving guideline concordant care.

The development and evaluation of a nationwide training program for oncology health professionals in the provision of genetic testing for ovarian cancer patients

BackgroundBRCA1/2 mutation status has increasing relevance for ovarian cancer treatments, making traditional coordination of genetic testing by genetic services unsustainable. Consequently alternative models of genetic testing have been developed to improve testing at the initial diagnosis for all eligible women. MethodsA training module to enable mainstreamed genetic testing by oncology healthcare professionals was developed by genetic health professionals. Oncology healthcare professionals completed questionnaires before and 12 months post-training to assess perceived skills, competence and barriers to their coordinating genetic testing for women with high-grade non-mucinous epithelial ovarian cancer. Genetic health professionals were surveyed 12 months post-training to assess perceived barriers to implementation of mainstreaming. Results185 oncology healthcare professionals were trained in 42 workshops at 35 Australasian hospitals. Of the 273 tests ordered by oncology healthcare professionals post-training, 241 (93.1%) met national testing guidelines. The number of tests ordered by genetic health professionals reduced significantly (z = 45.0, p = 0.008). Oncology healthcare professionals' perceived barriers to mainstreamed testing decreased from baseline to follow-up (t = 2.39, p = 0.023), particularly perceived skills, knowledge and attitudes. However, only 58% reported either ‘always’ or ‘nearly always’ having ordered BRCA testing for eligible patients at 12 months, suggesting oncology healthcare professionals' perceived barriers were not systematically addressed through training. ConclusionsOncology healthcare professionals have demonstrated a willingness to be involved in the provision of genetic testing in a mainstreaming model. If oncology services are to hold responsibility for coordinating genetic testing, their readiness will require understanding of barriers not addressed by training alone to inform future intervention design.

Abstract P6-08-38: Evaluation of adherence to NCCN guidelines regarding genetic evaluation of patients with breast or ovarian cancer diagnoses in a community hospital setting

Abstract Background: The National Comprehensive Cancer Network (NCCN) guidelines provide recommendations for which patients diagnosed with breast or ovarian cancer should have a referral for genetic evaluation. However, in a community setting without access to an on-site genetics provider, providing genetic counseling or testing could be more difficult. Objective: The study objective was to evaluate which patients within a community cancer program appropriate for genetic referral actually received counseling or testing, and identify any changes in practice after initiation of an on-site genetics program. Methods: Utilizing an institutional tumor registry database, patients from a community oncology program were identified who met a subset of NCCN guidelines for genetic referral from June 2015 through June 2017. Patients diagnosed with ovarian cancer, breast cancer diagnosed at or before age 45, male breast cancer, and triple negative breast cancer diagnosed at or before age 60 were included. A retrospective electronic chart review was performed to evaluate for genetic referral and uptake of genetic testing. Patients who received genetic testing prior to a cancer diagnosis were excluded from evaluation. Results: A total of 103 patients were included (35 ovarian cancer; 62 breast cancer ≤ age 45; 1 male breast cancer; 17 triple negative ≤ age 60). A total of 76 patients had genetic testing (74%). An additional 5 patients were offered genetic testing or referred for a genetic consult but declined, bringing the total referred or tested to 78.6%. Patients with breast cancer indications had the highest rate of genetic testing (88%). Patients with ovarian cancer were tested at a lower rate (45%). A secondary analysis was performed comparing the length of time between diagnosis and testing before and after the initiation of an on-site genetics program in late July 2016. For patients with breast cancer diagnosed at or under age 45, prior to on-site genetics availability, the average time to test was 62 days (6-1021 days, with 2 patients tested prior to their diagnosis). After the genetics program started, the average time to test was 23 days (6-141 days). For patients with triple negative breast cancer diagnosed at or under age 60, the time to test went from 106 days (8-767 days) to 29 days (6-116 days). For patients with ovarian cancer, time to test went from 296 days (80-810 days) to 116 days (13-230 days). Conclusions: Within our community cancer program, there was a reasonable rate of genetic referral or genetic testing for patients with breast cancer indications per a subset of the NCCN guidelines. The rates of referral or testing were worse for ovarian cancer patients, reflecting the more acute presentation of many of these patients. There exists opportunity for improvement for testing of ovarian cancer patients including availability of inpatient consultation or testing. In addition, this study did not evaluate those patients meeting NCCN guidelines for testing based on family history, which may reflect different referral or testing patterns. For all indications, the average time from diagnosis to testing decreased with the initiation of an on-site genetics program. Citation Format: Kristine M. King, Shannon Huffaker, Dione Froman. Evaluation of adherence to NCCN guidelines regarding genetic evaluation of patients with breast or ovarian cancer diagnoses in a community hospital setting [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-38.

Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives.

The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family members of ovarian cancer patients, is the identification of carriers of pathogenic variant, who have inheredited predisposition to cancer development (test for cancer risk). These individuals with increased risk of cancer, should be encouraged to participate in dedicated high-risk surveillance clinics and specific risk-reducing measures (primary and/or secondary prevention programs).

Germline genetic testing in ovarian cancer patients: Identifying barriers to care and opportunities for improvement.

e13142 Background: Despite recommendations that all patients with non-mucinous high grade epithelial ovarian cancer (EOC) undergo germline genetic testing, only 10-15% of patients nationwide are tested. The aim of this study was to determine the rate of genetic testing at a single academic institution, identify patient characteristics associated with undergoing testing and improve delivery of care by identifying barriers to testing. Methods: An IRB-approved single institution ovarian cancer database was used to identify patients with non-mucinous high grade EOC treated between 1996 and 2017. The rate of genetic testing was calculated and the referral and testing process was mapped. Patient demographics, clinical characteristics and family history was obtained from the medical record. Univariate and multivariate logistic regression was performed. Results: From 1996 to 2017, 588 patients were treated for non-mucinous EOC. Of those, 200 patients (34%) were referred for genetic counseling and 175 (30%) were tested. Younger patients were more likely to undergo testing. Fewer African Americans had genetic testing than Caucasians (18% vs 33%, p = 0.003) and patients with public insurance were less likely to undergo testing compared to those with private insurance (23% vs 34%, p = 0.005). Patients with recurrent disease were less likely to undergo testing but rates did not vary by cancer stage or histology. A family history of cancer was the most significant predictor (43% vs 11%, OR = 5.85, p &lt; 0.001). For patients diagnosed in the past 5 years, the testing rate improved to 57.9%. When the referral and testing process was mapped, a complex internal referral system was revealed. Barriers to testing included provider awareness, additional patient visits, patient preference and insurance coverage. Conclusions: Rates of germline genetic testing for patients with ovarian cancer have increased over time as guidelines for genetic testing have evolved, however, over two thirds of patients were not tested and African Americans were less likely to be tested. These findings support increasing provider education and patient counseling, testing directly in the gyn/oncology office and consideration for instituting a Traceback program.

Direct Genetics Referral Pathway for High-Grade Serous Ovarian Cancer Patients: The "Opt-Out" Process.

Purpose In order to meet a clinical need for better pathways to access genetic testing for ovarian cancer patients, we implemented and reviewed an opt-out referral process for genetic consultation whereby a referral is automatically sent to genetics following a pathological diagnosis of HGSC. Methods Following implementation of the opt-out referral process, each month a list of new cases of HGSC was generated from the synoptic pathology report and forwarded directly to the Cancer Genetics clinic. Using an advanced directive, patients were automatically referred for genetic counselling two months after surgery. If the patient declined genetic counselling (opted-out) after discussion with their surgeon within the two months after surgery, the Genetic Counsellor was informed and the patient was removed from the referral process. Results Between January 1, 2015, and December 31, 2017, 168 women were diagnosed with HGSC, of whom 167 received a referral for genetic consultation. In only one case the referral was cancelled by the surgeon, resulting in a referral rate of 99.4%. By the end of the study period, 133 women attended a genetics consultation appointment and 125 (94%) agreed to proceed with genetic testing. Among those who completed genetic testing, 15% tested positive for a BRCA1 or BRCA2 gene mutation. Of the women who tested positive for a BRCA1/2 mutation, 56% had no family history of breast or ovarian cancer. Conclusions The opt-out referral process described in this study is s a feasible, effective, and patient-centred approach to increase access to BRCA1/2 testing for patients with ovarian cancer.

Mainstreaming BRCA mutation testing for ovarian cancer patients: Addressing health inequalities.

e18526Background: The prevalence of germline BRCA mutations (BRCAm) in patients with high grade ovarian cancer (HGOC) is approximately 18%. In the era of therapeutic PARP inhibition, identifying BR...

Paired somatic and germline genetic testing for ovarian cancer patients: Observations, benefits and implications for treatment.

5579Background: Germline and somatic genetic testing have traditionally been offered separately; however, the clinical applications of these tests are now converging with continued FDA approval of ...

Germline and somatic genetic testing in ovarian cancer patients

Germline and somatic genetic testing in ovarian cancer patients

Main implications related to the switch to BRCA1/2 tumor testing in ovarian cancer patients: a proposal of a consensus.

BackgroundSince the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3–9% of patients with peculiar somatic BRCA1/2 mutations. These women could also benefit from PARPi therapy. This new type of approach is really challenging, in particular due to the technical and analytical difficulties regarding low quality DNA deriving from formalin-fixed, paraffin-embedded (FFPE) specimens.Aimin this manuscript, we try to a) underline many issues related to BRCA1/2 analysis by next generation sequencing technologies (NGS), b) provide some responses to many questions regarding this new paradigm related to OvCa patients’ management. Some considerations for incorporating genetic analysis of ovarian tumour samples into the patient pathway and ethical requirements are also provided.Methodswe used our retrospective data based on thousands of ovarian cancer women sequenced for BRCA1/2 genes.Discussiontumor BRCA1/2 assay should be rapidly introduced in routine laboratory practice as first line testing by using harmonized pipelines based on consensus guidelines.