Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study
Authors
Morgan, Robert DavidClamp, Andrew R
Barnes, Bethany M
Timms, K.
Schlecht, H.
Yarram-Smith, L.
Wallis, Y.
Valganon-Petrizan, M.
MacMahon, S.
White, R.
Morgan, S.
McKenna, S.
Hudson, E.
Tookman, L.
George, A.
Manchanda, R.
Sundar, S. S.
Nicum, S.
Brenton, J. D.
Kristeleit, R. S.
Banerjee, S.
McNeish, I. A.
Ledermann, J. A.
Taylor, S. S.
Evans, D. G. R.
Jayson, Gordon C
Affiliation
The Christie NHS Foundation Trust, Manchester, UKIssue Date
2023
Metadata
Show full item recordAbstract
Objective: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. Methods: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network. Results: The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p<0.0001). Conclusion: This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.Citation
Morgan RD, Clamp AR, Barnes BM, Timms K, Schlecht H, Yarram-Smith L, et al. Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2023 Apr 24. PubMed PMID: 37072323. Epub 2023/04/19. eng.Journal
International Journal of Gynecological CancerDOI
10.1136/ijgc-2022-004211PubMed ID
37072323Additional Links
https://dx.doi.org/10.1136/ijgc-2022-004211Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1136/ijgc-2022-004211
Scopus Count
Collections
Related articles
- Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.
- Authors: Schouten PC, Schmidt S, Becker K, Thiele H, Nürnberg P, Richters L, Ernst C, Treilleux I, Medioni J, Heitz F, Pisano C, Garcia Y, Petru E, Hietanen S, Colombo N, Vergote I, Nagao S, Linn SC, Pujade-Lauraine E, Ray-Coquard I, Harter P, Hahnen E, Schmutzler RK
- Issue date: 2024 Apr 1
- In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay.
- Authors: Fumagalli C, Betella I, Ranghiero A, Guerini-Rocco E, Bonaldo G, Rappa A, Vacirca D, Colombo N, Barberis M
- Issue date: 2022 Aug
- Systematic Analysis of Homologous Recombination Deficiency Testing in Ovarian Cancer-Development of Recommendations for Optimal Assay Performance.
- Authors: Romey M, Rodepeter F, Hattesohl A, Kaiser K, Teply-Szymanski J, Heitz F, Staebler A, Serra V, Grass A, Marmé F, Timms KM, Harter P, Llop-Guevara A, Kommoss S, Boekhoff J, Denkert C
- Issue date: 2024 Apr
- Ovarian high-grade serous carcinoma with transitional-like (SET) morphology: a homologous recombination-deficient tumor.
- Authors: D'Angelo E, Espinosa I, Felicioni L, Buttitta F, Prat J
- Issue date: 2023 Nov
- Concordance between an FDA-approved companion diagnostic and an alternative assay kit for assessing homologous recombination deficiency in ovarian cancer.
- Authors: Wehn AK, Qiu P, Lunceford J, Yarunin A, Cristescu R, Liu L, Roessler K, Bilke S, Day JR, Timms KM, Weichert W, Marton MJ
- Issue date: 2024 May