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Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

ABSTRACT: Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic BRCA variants, but also BRCAwt/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad's. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of PTEN and EMSY. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing.

SUBMITTER: Magliacane G

PROVIDER: S-EPMC9817883 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

Magliacane Gilda G Brunetto Emanuela E Calzavara Silvia S Bergamini Alice A Pipitone Giovanni Battista GB Marra Giovanna G Redegalli Miriam M Grassini Greta G Rabaiotti Emanuela E Taccagni Gianluca G Pecciarini Lorenza L Carrera Paola P Mangili Giorgia G Doglioni Claudio C Cangi Maria Giulia MG

Cancers 20221221 1

Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic <i>BRCA</i> variants, but also <i>BRCAwt</i>/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but t ...[more]

PMID: 36612041

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Project description:IntroductionOvarian cancer (OC) is the eighth most common cancer among women, and homologous recombination deficiency (HRD) is present in approximately 50% of these patients. For this group, poly(ADP-ribose) polymerase (PARP) inhibitors are more likely to be effective. The aim of the study was to investigate the cost-effectiveness of HRD testing versus BRCA testing (which identifies mutations present only in 25% of patients) in Italy to optimize the treatment management, possibly with PARP inhibitors.MethodsA cost-effectiveness partition survival model was developed to estimate the expected costs and outcomes (life years, LYs; quality-adjusted life years, QALYs) with lifetime horizon of HRD testing versus BRCA testing alone in women with high-grade serous or endometrioid advanced ovarian cancer. The option to perform the tests in sequence, that is, the BRCA test followed by the HRD test, in patients with BRCA-negative test was also considered, and the model accounted for the National Healthcare Service (NHS) perspective in Italy. The treatments represented the best available options according to the initial test results and according to PARP inhibitors available in Italy. A 3% discount rate was applied. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model results.ResultsHRD testing was shown to be a cost-effective strategy compared to BRCA testing (incremental cost-utility ratio 22,610€/QALY) and a cost-saving strategy compared to the sequence of tests. The probabilistic sensitivity analysis showed that the HRD test is cost-effective compared to BRCA testing in 98.5% of model simulations considering a willingness-to-pay threshold of 50,000€/QALY.ConclusionThe identification of genetic anomalies in patients with advanced OC is a costly process. Regardless, HRD upfront testing compared to BRCA testing had a cost-effective profile, allowing the efficient use of healthcare resources and better life expectancy and quality of life for patients.

Project description:The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the BRCA1/2 status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice® test on all the patients with an indication for tumor HRD testing. Germline testing was conducted on all the patients using the TruRisk® panel as recommended by the national guidelines. HRD testing was requested for 190 patients, and, for 163 patients (85.8%), an HRD test result was available. An HRD test result could not be reported in 27 patients due to an insufficient tumor yield. The median time that it took to receive the HRD test results was 37 days (range of 8-97). In total, an HRD was present in 44.7% (73/163) of the patients based on a GIS ≥ 42 in 42.9% of the patients and based on a tumor BRCA1/2 mutation in 3 cases (all with a GIS < 42). The germline testing results were available for 148 patients, and, in 18 patients (12.2%), a deleterious germline mutation was detected. Of the 27 patients without sufficient HRD testing, BRCA1/2 germline testing results were available for 19 patients (70.4%), and a deleterious germline mutation was detected in 2 patients (7.4%). The implementation of HRD testing is feasible, and the results become available for treatment decisions in a timely manner for most patients. The prerequisite for HRD testing with the Myriad myChoice® test is a sufficient amount of tumor tissue. The cotesting of HRD and BRCA1/2 germline testing should be aimed for in order to enable optimal and timely treatment decisions on maintenance therapy as well as to test patients on whom the HRD test will not be evaluable.

Project description:Parallel genetic testing (testing for both tumour and germline gene changes) after the diagnosis of ovarian cancer should be considered the standard of care and is crucial to support treatment decisions. The demonstration of improvement for molecular ovarian cancer testing (DEMO) project aimed to develop patient-focused tools to promote equitable genetic care in diverse communities with high proportions of patients with limited English proficiency and biopsy guidelines to address the variations in specimen quality in different geographical regions in the UK. Our three work packages (WP) aimed to promote awareness by addressing the information gaps in different community groups (WP1), develop infrastructure to evaluate the different tissue collection pathways in different regions (WP2) and support continuing professional development (CPD) to encourage best practices with the involvement of patients (WP3). Our output included a multimedia multilanguage information package with paired National Health Service-branded written materials to support genetic testing after ovarian cancer diagnosis (https://ovarian.org.uk/demo-uk/), a scalable database to enable a multisite audit of parallel genetic testing pathways and a collection of CPD events that had patient involvement as an essential component. In addition, we have collaborated with patient and community groups to contribute to a national consensus guidance on genetic testing in ovarian cancer. Our co-production work has been recognised by local and regional awards as an exemplar for patient and public involvement (PPI). This has supported the start of a legacy co-production group in gynaeoncology (https://www.dhlnetwork.com/gohildas) to address the critical unmet need for sustainable and equity-oriented PPI to advocate for underserved communities. The DEMO project has contributed to raising awareness of the importance of equitable genetic care in ovarian cancer. We will continue to build on this groundwork to support future quality improvement projects and research, with the ultimate goal of improving the outcomes of patients with ovarian cancer.

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Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

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Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

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