4 results on '"El-Khouly, Fatima"'
Search Results
2. 2022-RA-1310-ESGO Cost-effectiveness of unselected multigene germline and somatic genetic testing for epithelial ovarian cancer
- Author
-
Sun, Li, primary, Sobocan, Monika, additional, Rodriguez, Isabel V, additional, Wei, Xia, additional, Kalra, Ashwin, additional, Oxley, Samuel, additional, Sideris, Michail, additional, Morgan, Robert D, additional, Chandrasekaran, Dhivya, additional, Rust, Kelly, additional, Spiliopoulou, Pavlina, additional, Miller, Rowan E, additional, Crusz, Shanthini M, additional, Lockley, Michelle, additional, Singh, Naveena, additional, Faruqi, Asma, additional, Casey, Laura, additional, Brockbank, Elly, additional, Phadnis, Saurabh, additional, Mills-Baldock, Tina, additional, El-Khouly, Fatima, additional, Jenkins, Lucy A, additional, Wallace, Andrew, additional, Ahmed, Munaza, additional, Kumar, Ajith, additional, Swisher, Elizabeth M, additional, Gourley, Charlie, additional, Norquist, Barbara M, additional, Gareth Evans, D, additional, Legood, Rosa, additional, and Manchanda, Ranjit, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.
- Author
-
Chandrasekaran, Dhivya, Sobocan, Monika, Blyuss, Oleg, Miller, Rowan E., Evans, Olivia, Crusz, Shanthini M., Mills-Baldock, Tina, Sun, Li, Hammond, Rory F. L., Gaba, Faiza, Jenkins, Lucy A., Ahmed, Munaza, Kumar, Ajith, Jeyarajah, Arjun, Lawrence, Alexandra C., Brockbank, Elly, Phadnis, Saurabh, Quigley, Mary, El Khouly, Fatima, and Wuntakal, Rekha
- Subjects
GENETIC mutation ,OVARIAN epithelial cancer ,BRCA genes ,GENETIC testing ,GENOMICS ,HEALTH care teams ,DESCRIPTIVE statistics ,NURSE practitioners ,GENETIC counseling - Abstract
Simple Summary: Multigene testing in ovarian cancer has received increased support due to its' applicability for cancer treatment and the impact it has on cancer prevention in families. This study shows that multi-gene germline and somatic testing uptake after counselling by a member of the multidisciplinary cancer clinical team in women with ovarian cancer, was high (97%). A total of 15.5% of women were identified to have germline BRCA1/BRCA2 pathogenic variants and 7.8% had somatic BRCA1/BRCA2 pathogenic variants. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 pathogenic variants. We found that 11% of germline pathogenic variants were large-genomic-rearrangements and were missed by somatic testing. Our findings support prospective parallel somatic-&-germline panel testing to maximize variant identification. We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.
- Author
-
Manchanda R, Sun L, Sobocan M, Rodriguez IV, Wei X, Kalra A, Oxley S, Sideris M, Fierheller CT, Morgan RD, Chandrasekaran D, Rust K, Spiliopoulou P, Miller RE, Crusz SM, Lockley M, Singh N, Faruqi A, Casey L, Brockbank E, Phadnis S, Mills-Baldock T, El-Khouly F, Jenkins LA, Wallace A, Ahmed M, Kumar A, Swisher EM, Gourley C, Norquist BM, Evans DG, and Legood R
- Subjects
- Humans, Female, Genetic Predisposition to Disease, BRCA2 Protein genetics, BRCA1 Protein genetics, Middle Aged, United States epidemiology, Quality-Adjusted Life Years, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Poly(ADP-ribose) Polymerase Inhibitors economics, RNA Helicases genetics, Adult, United Kingdom epidemiology, Fanconi Anemia Complementation Group Proteins genetics, DNA-Binding Proteins, Cost-Benefit Analysis, Genetic Testing economics, Genetic Testing methods, Germ-Line Mutation, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial economics, Carcinoma, Ovarian Epithelial diagnosis, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial pathology, Ovarian Neoplasms genetics, Ovarian Neoplasms drug therapy, Ovarian Neoplasms diagnosis, Ovarian Neoplasms economics
- Abstract
Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone., Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated., Results: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths., Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.