Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer : a multi-national observational study
Author
Morgan, Robert DClamp, Andrew R
Barnes, Bethany M
Timms, Kirsten
Schlecht, Helene
Yarram-Smith, Laura
Wallis, Yvonne
Valganon-Petrizan, Mikel
MacMahon, Suzanne
White, Rhian
Morgan, Sian
McKenna, Sarah
Hudson, Emma
Tookman, Laura
George, Angela
Manchanda, Ranjit
Sundar, Sudha
Nicum, Shibani
Brenton, James D
Kristeleit, Rebecca S
Banerjee, Susana
McNeish, Iain A
Ledermann, Jonathan A
Taylor, Stephen S
Evans, D Gareth R
Jayson, Gordon C
Affiliation
The Christie NHS Foundation Trust; University of Manchester; Myriad Genetics; Sandwell and West Birmingham NHS Trust; et al.Publication date
2023-08-07
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, Wallis Y, Valganon-Petrizan M, MacMahon S, White R, Morgan S, McKenna S, Hudson E, Tookman L, George A, Manchanda R, Sundar SS, Nicum S, Brenton JD, Kristeleit RS, Banerjee S, McNeish IA, Ledermann JA, Taylor SS, Evans DGR, Jayson GC. Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study. Int J Gynecol Cancer. 2023 Aug 7;33(8):1253-1259. doi: 10.1136/ijgc-2022-004211Type
ArticlePMID
37072323Publisher
BMJ Publishing Groupae974a485f413a2113503eed53cd6c53
10.1136/ijgc-2022-004211