학술논문
Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study.
Document Type
Academic Journal
Author
Morgan RD; The Christie NHS Foundation Trust, Manchester, UK robert.morgan7@nhs.net.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Clamp AR; The Christie NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Barnes BM; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Timms K; Myriad Genetics, Inc, Salt Lake City, Utah, USA.; Schlecht H; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.; Yarram-Smith L; South West Genomic Laboratory Hub, North Bristol NHS Trust, Bristol, UK.; Wallis Y; Central and South Genomic Laboratory Hub, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.; Valganon-Petrizan M; North Thames Genomic Laboratory Hub, The Royal Marsden Hospital NHS Foundation Trust, Surrey, UK.; MacMahon S; North Thames Genomic Laboratory Hub, The Royal Marsden Hospital NHS Foundation Trust, Surrey, UK.; White R; All Wales Genomics Laboratory, Institute of Medical Genetics, University Hospital Wales, Cardiff, UK.; Morgan S; All Wales Genomics Laboratory, Institute of Medical Genetics, University Hospital Wales, Cardiff, UK.; McKenna S; Belfast Health and Social Care Trust, Belfast, UK.; Hudson E; Velindre University NHS Trust, Cardiff, UK.; Tookman L; Imperial College Healthcare NHS Trust, London, UK.; George A; The Royal Marsden NHS Foundation Trust, London, UK.; The Institute of Cancer Research, London, UK.; Manchanda R; Barts Health NHS Trust, London, UK.; Department of Health Services Research, The Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Wolfson Institute of Population Health, Queen Mary's University of London, London, UK.; Sundar SS; Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; Nicum S; University College London Hospitals NHS Foundation Trust, London, UK.; UCL Cancer Institute, London, UK.; Brenton JD; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.; Kristeleit RS; Guy's and St Thomas' NHS Foundation Trust, London, UK.; Banerjee S; The Royal Marsden NHS Foundation Trust, London, UK.; The Institute of Cancer Research, London, UK.; McNeish IA; Imperial College Healthcare NHS Trust, London, UK.; Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.; Ledermann JA; University College London Hospitals NHS Foundation Trust, London, UK.; UCL Cancer Institute, London, UK.; Taylor SS; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Evans DGR; Manchester University NHS Foundation Trust, Manchester, UK.; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Jayson GC; The Christie NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Source
Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
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 BRCA 1/2 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.
Competing Interests: Competing interests: RDM, BMB, HS, LY-S, YW, MV-P, RW, SM, SMc, EH, AG, SS, SN, SST and DGRE declare no conflicts of interest. KT is an employee and stockholder of Myriad Genetics, Inc. ARC declares research funding from AstraZeneca. SMac declares travel funding and speaker fees from AstraZeneca, Merck and Eli Lily. LT declares honoraria from AstraZeneca, Clovis Oncology, GSK and Tesaro. RM declares honoraria from AstraZeneca, Merck Sharp & Dohme and GSK and research funding from Barts & The London Charity, Rosetrees Trust, GSK and Yorkshire Cancer Research. JDB declares honoraria from AstraZeneca and GSK and consulting and advisory roles in Clovis Oncology and GSK. SB declares institutional grants from AstraZeneca and GSK, personal fees for speaker, consulting/advisory roles from Amgen, AstraZeneca, Clovis Oncology, Epsilogen, GSK, Immunogen, Mersana, Merck Sharp & Dohme, Merck Serono, Novartis, OncXerna, Pfizer, Roche, Shattuck Labs & Takeda. RSK declares honoraria from AstraZeneca, Clovis Oncology, GSK and Incyte and travel support from AstraZeneca, GSK and Sierra Oncology and trial grants from Merck Sharp & Dohme and consulting fees from Basilea Pharmaceutica and Shattuck Pharma. IMcN declares honoraria from AstraZeneca, Clovis Oncology, Epsila Bio, GSK, Roche and Scancell and institutional funding from AstraZeneca. JAL declares honoraria from AstraZeneca, Clovis Oncology, GSK, Eisai, Neopharm, Artios Pharma, Merck/Merck Sharp & Dohme, Mersana, Regeneron, VBL Therapeutics, Nuvation and Bristol Myers Squibb. GCJ declares research funding from AstraZeneca.
(© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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 BRCA 1/2 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, χ
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.
Competing Interests: Competing interests: RDM, BMB, HS, LY-S, YW, MV-P, RW, SM, SMc, EH, AG, SS, SN, SST and DGRE declare no conflicts of interest. KT is an employee and stockholder of Myriad Genetics, Inc. ARC declares research funding from AstraZeneca. SMac declares travel funding and speaker fees from AstraZeneca, Merck and Eli Lily. LT declares honoraria from AstraZeneca, Clovis Oncology, GSK and Tesaro. RM declares honoraria from AstraZeneca, Merck Sharp & Dohme and GSK and research funding from Barts & The London Charity, Rosetrees Trust, GSK and Yorkshire Cancer Research. JDB declares honoraria from AstraZeneca and GSK and consulting and advisory roles in Clovis Oncology and GSK. SB declares institutional grants from AstraZeneca and GSK, personal fees for speaker, consulting/advisory roles from Amgen, AstraZeneca, Clovis Oncology, Epsilogen, GSK, Immunogen, Mersana, Merck Sharp & Dohme, Merck Serono, Novartis, OncXerna, Pfizer, Roche, Shattuck Labs & Takeda. RSK declares honoraria from AstraZeneca, Clovis Oncology, GSK and Incyte and travel support from AstraZeneca, GSK and Sierra Oncology and trial grants from Merck Sharp & Dohme and consulting fees from Basilea Pharmaceutica and Shattuck Pharma. IMcN declares honoraria from AstraZeneca, Clovis Oncology, Epsila Bio, GSK, Roche and Scancell and institutional funding from AstraZeneca. JAL declares honoraria from AstraZeneca, Clovis Oncology, GSK, Eisai, Neopharm, Artios Pharma, Merck/Merck Sharp & Dohme, Mersana, Regeneron, VBL Therapeutics, Nuvation and Bristol Myers Squibb. GCJ declares research funding from AstraZeneca.
(© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)