Cost comparison among different genetic testing strategies in women with epithelial ovarian cancer

Purpose: The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies. Methods: A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed. Results: No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs. Conclusion: MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.

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Preferences of women with epithelial ovarian cancer for aspects of genetic testing

Gynecologic Oncology Research and Practice ◽

10.1186/s40661-019-0066-8 ◽

2019 ◽

Vol 6 (1) ◽

Cited By ~ 3

Author(s):

Brittany A. Davidson ◽

Jessie Ehrisman ◽

Shelby D. Reed ◽

Jui-Chen Yang ◽

Adam Buchanan ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer

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Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline

Journal of Clinical Oncology ◽

10.1200/jco.19.02960 ◽

2020 ◽

Vol 38 (11) ◽

pp. 1222-1245 ◽

Cited By ~ 21

Author(s):

Panagiotis A. Konstantinopoulos ◽

Barbara Norquist ◽

Christina Lacchetti ◽

Deborah Armstrong ◽

Rachel N. Grisham ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer ◽

Health Care Providers ◽

Systematic Reviews ◽

Clinical Decision Making ◽

Cancer Susceptibility ◽

Care Providers ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes

PURPOSE To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus. METHODS A literature search and prospectively defined study selection criteria sought systematic reviews, meta-analyses, randomized controlled trials (RCTs), and comparative observational studies published from 2007 through 2019. Guideline recommendations were based on the review of the evidence. RESULTS The systematic review identified 19 eligible studies. The evidence consisted of systematic reviews of observational data, consensus guidelines, and RCTs. RECOMMENDATIONS All women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes. In women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants should be performed. Women with identified germline or somatic pathogenic or likely pathogenic variants in BRCA1/2 genes should be offered treatments that are US Food and Drug Administration (FDA) approved in the upfront and the recurrent setting. Women diagnosed with clear cell, endometrioid, or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. First- or second-degree blood relatives of a patient with ovarian cancer with a known germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation, counseling, and genetic testing. Clinical decision making should not be made based on a variant of uncertain significance. Women with epithelial ovarian cancer should have testing at the time of diagnosis.

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Epithelial Ovarian Cancer Metastatic to the Central Nervous System and a Family History Concerning for Hereditary Breast and Ovarian Cancer—A Potential Relationship

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000489 ◽

2015 ◽

Vol 25 (7) ◽

pp. 1232-1238 ◽

Cited By ~ 7

Author(s):

Amelia M. Jernigan ◽

Haider Mahdi ◽

Peter G. Rose

Keyword(s):

Ovarian Cancer ◽

Central Nervous System ◽

Nervous System ◽

Genetic Testing ◽

Family History ◽

Epithelial Ovarian Cancer ◽

Survival Outcomes ◽

Breast And Ovarian Cancer ◽

Cns Metastasis ◽

Potential Relationship

ObjectivesTo estimate the frequency of hereditary breast and ovarian cancer (HBOC) in women with central nervous system (CNS) metastasis from epithelial ovarian cancer (EOC) and to evaluate for a potential relationship between HBOC status and survival.Methods and MaterialsA total of 1240 cases of EOC treated between 1995 and 2014 were reviewed to identify CNS metastasis. Demographics, treatment, family history, genetic testing, and survival outcomes were recorded. Women were then classified as HBOC+ or HBOC− based on histories and genetic testing results. Kaplan-Meier survival curves and univariable Cox proportional hazards models were used.ResultsOf 1240 cases, 32 cases of EOC with CNS metastasis were identified (2.58%). Median age was 52.13 (95% confidence interval [CI], 40.56–78.38) years, and 87.10% had stage III to IV disease. Among those with documented personal and family history, 66.7% (20/30) were suspicious for HBOC syndrome. Among those who underwent germline testing, 71.43% (5/7) had a pathogenic BRCA mutation. The median time from diagnosis to CNS metastasis was 29.17 (95% CI, 0–187.91) months. At a median survival of 5.97 (95% CI, 0.20–116.95) months from the time of CNS metastasis and 43.76 (95% CI, 1.54-188.44) months from the time of EOC diagnosis, 29 women died of disease. Univariate Cox proportional hazard models were used to compare HBOC− to HBOC+ women and did not reveal a significant difference for survival outcomes.ConclusionsConfirmed BRCA mutations and histories concerning for HBOC syndrome are common in women with EOC metastatic to the CNS. We did not demonstrate a relationship between HBOC status and survival outcomes, but were not powered to do so.

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Effects of initiating in-office germline testing in safety net clinic patients with epithelial ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1588 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1588-1588

Author(s):

Scott Jordan ◽

Samantha Spring ◽

Matthew Schlumbrecht ◽

Marilyn Huang

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Maintenance Therapy ◽

Epithelial Ovarian Cancer ◽

Intervention Group ◽

Safety Net ◽

Clinic Visit ◽

Control Group ◽

Test Results ◽

Germline Testing

1588 Background: Germline genetic mutations occur in approximately 25% of women with epithelial ovarian cancers. Recent advances in frontline maintenance therapy for patients with hereditary breast and ovarian cancer syndrome make timely germline testing critical. Adherence to genetic testing remains low (approximately 30% nationally), including at our safety net hospital where germline testing by a genetic counselor was performed in only 38% of patients. After initiating in-office genetic testing, our aim was to compare current patients with historical controls to determine whether this intervention shortened the time to testing and results. Methods: IRB approval was obtained. Patients seen for a diagnosis of epithelial ovarian cancer between 4/1/2018 and 12/31/2019 were identified. Patients with only one visit or those who received testing elsewhere were excluded. Patient and visit data were abstracted for each visit during the study period. Comparison was made between patients treated before (control cohort) and after in-office testing was initiated (intervention cohort) on 5/21/2019. Categorical variables were compared using Chi Squared and Fisher’s Exact test. Mann Whitney U test was used to compare time from first clinic visit to the date of genetic testing and to the reporting of test results in the chart. All tests were two-sided and significance was set at p = 0.05. Results: 74 patients were identified and 504 clinic visits were analyzed. 57 (77%) patients were White Hispanic, 15 (20.3%) were Black, and 2 (2.7%) were White non-Hispanic. 56 (75.7%) underwent germline testing. Overall median time to testing from the first clinic visit was 21.2 weeks, and median time to reporting of results was 37 weeks. Though there was no significant difference in testing rate between the cohorts, the time to the date of genetic testing in the intervention group was approximately one-third as long as in the control group (9.6 vs 32.1 weeks, p < 0.001). Among the 52 patients with reported genetic results, results were recorded in a clinic note at 4.1 weeks from first visit in the intervention group, compared with 28.8 weeks in the control group (p < 0.001). In the intervention group, during clinic visits without genetics performed to date, testing was performed at that visit 25% of the time. Conclusions: By initiating in-office testing, time to testing and receipt of results were meaningfully shortened. Removing delays to test results will greatly improve the ability of our patients to receive potentially life-saving maintenance therapy following front line treatment.

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Genetic testing for epithelial ovarian cancer

Best Practice & Research Clinical Obstetrics & Gynaecology ◽

10.1016/j.bpobgyn.2020.01.005 ◽

2020 ◽

Vol 65 ◽

pp. 125-138

Author(s):

Noa Amin ◽

Narda Chaabouni ◽

Angela George

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer

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Spectrum of Germline Pathogenic Variants in BRCA1/2 Genes in the Apulian Southern Italy Population: Geographic Distribution and Evidence for Targeted Genetic Testing

Cancers ◽

10.3390/cancers13184714 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4714

Author(s):

Margherita Patruno ◽

Simona De Summa ◽

Nicoletta Resta ◽

Mariapia Caputo ◽

Silvia Costanzo ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Geographic Distribution ◽

Southern Italy ◽

Brca1 Gene ◽

Breast And Ovarian Cancer ◽

Pathogenic Variants ◽

Testing Strategies ◽

Brca1 Brca2 ◽

Over Time

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.

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Addendum: Shin, W.; et al. The Knowledge and Attitude of Patients Diagnosed with Epithelial Ovarian Cancer towards Genetic Testing. Int. J. Environ. Res. Public Health 2021, 18, 2312

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084043 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4043

Author(s):

Wonkyo Shin ◽

Gowoon Jeong ◽

Yedong Son ◽

Sang-Soo Seo ◽

Sokbom Kang ◽

...

Keyword(s):

Public Health ◽

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer ◽

Environmental Research ◽

Knowledge And Attitude

The authors would like to add the following information to the “Funding” section of their paper published in the International Journal of Environmental Research and Public Health [...]

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Germline testing and somatic tumor testing for BRCA1/2 pathogenic variants in ovarian cancer: What is the optimal sequence of testing?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10585 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10585-10585

Author(s):

Janice S. Kwon ◽

Anna Tinker ◽

Jennifer Santos ◽

Katie Compton ◽

Sophie Sun ◽

...

Keyword(s):

Ovarian Cancer ◽

Monte Carlo Simulation ◽

Monte Carlo ◽

Cost Effectiveness ◽

Family History ◽

Epithelial Ovarian Cancer ◽

Parp Inhibitor ◽

Cost Effective ◽

Testing Strategies ◽

Germline Testing

10585 Background: In 2020 ASCO recommended that all women with epithelial ovarian cancer have germline testing (GT) for BRCA1/2 mutations, and those without a germline pathogenic variant (PV) should have somatic tumor testing (TT), to determine eligibility for PARP inhibitor (PARPi) therapy (GT-TT strategy). An alternate strategy is to start with tumor testing first, and to conduct germline testing only in those with a PV in the tumor, or a significant family history (TT-GT strategy). The objective was to conduct a cost-effectiveness analysis comparing the 2 testing strategies. Methods: A Markov Monte Carlo simulation model compared the costs (USD) and benefits of the 2 testing strategies. According to local empiric data, a sufficient tissue sample for TT was available in 99% of cases, otherwise the patient would only have GT. Sensitivity of TT was 99% for detecting germline PV. Only those with BRCA1/2 PV were eligible for PARPi. Primary outcomes included the number of women eligible for PARPi, with progression-free years of life (PFLY) gained based on SOLO1 data, and the incremental cost-effectiveness ratio (ICER). Monte Carlo simulation estimated the number of women who would have GT and TT, and the total with germline or somatic BRCA1/2 PV eligible for PARPi. Sensitivity analyses accounted for uncertainty around various parameters. Results: The GT-TT strategy was more effective but more costly than TT-GT in identifying patients eligible for PARPi. Table summarizes the average lifetime costs, benefits, and Monte Carlo simulation estimates for 10,000 women diagnosed with advanced epithelial ovarian cancer annually in the USA. The incremental benefit from the GT-TT strategy would be achieved at substantial cost to the health care system, with an ICER of $119,340 per PFLY gained relative to the TT-GT strategy. The results were highly sensitive to the sensitivity of TT to detect germline PV, and the costs of GT and TT. Assuming that GT was less than 50% of the cost of TT, the sensitivity of TT had to exceed 98% for the TT-GT strategy to be cost-effective. Conclusions: Although the ASCO recommended strategy of BRCA germline testing followed by tumor testing for those without a pathogenic variant may be more effective in identifying ovarian cancer patients for PARP inhibitor therapy, it is more costly. The ASCO strategy is justified if the sensitivity of tumor testing is not sufficiently high. However, assuming high tumor testing performance rates, tumor testing first followed by germline testing if there is a PV in the tumor and/or family history is a cost-effective strategy.[Table: see text]

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