I Vergote1, A González-Martín2, I Ray-Coquard3, P Harter4, N Colombo5, P Pujol6, D Lorusso7, M R Mirza8, B Brasiuniene9, R Madry10, J D Brenton11, M G E M Ausems12, R Büttner13, D Lambrechts14. 1. Division of Gynaecological Oncology, Department of Gynaecology and Obstetrics and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Electronic address: ignace.vergote@uzleuven.be. 2. Clinica Universidad de Navarra, Madrid, Spain; Program for Solid Tumors at Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain. 3. Medical Oncology, Centre Leon Bérard and Université Claude Bernard Lyon, Lyon, France. 4. Department of Gynaecology & Gynaecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, Germany. 5. University of Milan-Bicocca and European Institute of Oncology IRCCS, Milan, Italy. 6. Montpellier Faculty of Medicine, University Hospital of Montpellier, Montpellier, France. 7. Department of Women and Child Science and Public Health, Catholic University of Rome, Fondazione Policlinico Gemelli IRCCS, Rome, Italy. 8. Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 9. Department of Medical Oncology, National Cancer Institute of Lithuania, Faculty of Medicine of Vilnius University, Vilnius, Lithuania. 10. Oncological Gynaecology Department, Poznan University of Medical Sciences, Poznan, Poland. 11. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. 12. Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. 13. Institute of Pathology, University Hospital Cologne, Cologne, Germany. 14. Department of Human Genetics, VIB and KU Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. DESIGN: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. CONCLUSION: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. DESIGN: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. CONCLUSION: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
Authors: Pan Li; Chaohu Chen; Jianpeng Li; Li Yang; Yuhan Wang; Zhilong Dong; Jun Mi; Yunxin Zhang; Juan Wang; Hanzhang Wang; Ronald Rodriguez; Junqiang Tian; Zhiping Wang Journal: Front Genet Date: 2022-04-26 Impact factor: 4.772