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The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to ovarian cancer incidence.
In BRCA1/2 gene mutation carriers, a risk-reducing salpingo-oophorectomy (RRSO) is recommended around the age of 40. This recommendation is based on a 10-40% life-time risk of ovarian cancer in this population and disappointing results of ovarian cancer surveillance for early detection. Moreover, the mortality rate of ovarian cancer is high. Effects of RRSO are a decrease in ovarian cancer risk (80-96%) on one hand and immediate onset of menopause and non-cancer related morbidity on the other hand. The fifty percent breast cancer risk reduction after RRSO has become disputable in the last years. Based on multiple studies showing that most high-grade serous ovarian cancers develop at the distal end of the Fallopian tube, an innovative strategy for RRSO has been developed for this study proposal: risk-reducing salpingectomy (RRS) with delayed risk-reducing oophorectomy (RRO). However, the safety of this strategy has not been proven yet. Before implementing this innovative strategy as standard care we need to investigate the long term effects on ovarian cancer incidence.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Risk-reducing salpingectomy with delayed oophorectomy | Experimental | Risk-reducing salpingectomy after the completion of childbearing with delayed oophorectomy. |
|
| Risk-reducing salpingo-oophorectomy | Active Comparator | Risk-reducing salpingo-oophorectomy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Risk-reducing salpingectomy with delayed oophorectomy | Procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| High grade serous (ovarian) cancer incidence | High grade serous (ovarian) cancer incidence | Until the age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of (pre)malignant findings in tubes/ovaries | Incidence of (pre)malignant findings in tubes/ovaries at risk-reducing salpingectomy, oophorectomy and salpingo-oophorectomy. | 6 weeks after each surgery |
| Peri-operative morbidity and mortality |
| Measure | Description | Time Frame |
|---|---|---|
| High grade serous (ovarian) cancer incidence at the age of 70 | Exploratory outcome measure | Up to the age of 70 |
Inclusion Criteria:
Women with a class 5 (definitely pathogenic) BRCA1, BRCA2, RAD51C, RAD51D or BRIP1 germline mutation in one of the participating centers.
Age at inclusion;
Childbearing completed
Presence of at least one fallopian tube
Participants may have a personal history of non-ovarian malignancy
Informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joanne A. de Hullu, MD, PhD | Contact | +31 (0) 24 36 16683 | Joanne.deHullu@radboudumc.nl | |
| Karen H. Lu, MD, PhD | Contact | (713) 745-8902 | khlu@mdanderson.org |
| Name | Affiliation | Role |
|---|---|---|
| Joanne A. de Hullu, MD, PhD | Radboud University Medical Center | Principal Investigator |
| Karen H. Lu, MD, PhD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UChicago Medicine | Recruiting | Chicago | Illinois | 60637 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39509704 | Derived | Pennington KP, Pugh SL, Huh W, Walker JL, Jewell E, Havrilesky LJ, Carter J, Muller CY, Drapkin R, Lankes HA, Castellano T, Zamorano AS, Blank SV, Kachnic LA. Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy. Obstet Gynecol. 2025 Jan 1;145(1):21-30. doi: 10.1097/AOG.0000000000005781. Epub 2024 Nov 7. | |
| 37045546 |
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|
| Risk-reducing salpingo-oophorectomy | Procedure |
|
|
Peri-operative morbidity and mortality
| 6 weeks after each surgery |
| Incidence of pelvic cancer (other than ovarian cancer) | Incidence of pelvic cancer (other than ovarian cancer) | Up to the age of 70 |
| Incidence of breast cancer | Incidence of breast cancer | Up to the age of 70 |
| Uptake of risk reducing oophorectomy | Uptake of risk reducing oophorectomy after risk reducing salpingectomy | Up to the age of 70 |
| Rosella P.M.G. Hermens, MD,PhD |
| Radboud University Medical Center |
| Principal Investigator |
| Elizabeth M. Swisher, MD, PhD | University of Washington | Principal Investigator |
| Dana Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
|
| Mayo Clinic | Recruiting | Rochester | Minnesota | 55905 | United States |
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| Washington University Medical Center | Recruiting | St Louis | Missouri | 63110 | United States |
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| Mount Sinai Hospital | Recruiting | New York | New York | 10029 | United States |
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| Memorial Sloan Kettering Cancer Center | Recruiting | New York | New York | 10065 | United States |
|
| Duke University Hospital | Recruiting | Durham | North Carolina | 27705 | United States |
|
| Hospital of the University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
|
| Harris Health Lyndon B. Johnson Hospital | Recruiting | Houston | Texas | 77026 | United States |
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| MD Anderson Cancer Centre | Recruiting | Houston | Texas | 77030-4009 | United States |
|
| University of Washington | Recruiting | Seattle | Washington | 98195 | United States |
|
| Chris O'Brien Lifehouse | Recruiting | Sydney | New South Wales | 2050 | Australia |
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| Westmead hospital | Recruiting | Sydney | New South Wales | 2145 | Australia |
|
| St Andrew War Memorial Hospital | Recruiting | Brisbane | Queensland | 4001 | Australia |
|
| Royal Brisbane Hospital | Recruiting | Brisbane | Queensland | 4006 | Australia |
|
| Greenslopes Private Hospital | Recruiting | Brisbane | Queensland | 4120 | Australia |
|
| Royal Adelaide Hospital | Recruiting | Adelaide | South Australia | 5000 | Australia |
|
| Frances Perry House | Recruiting | Melbourne | Victoria | 3050 | Australia |
|
| Mercy Hospital | Recruiting | Melbourne | Victoria | 3084 | Australia |
|
| Epworth Hospital | Recruiting | Richmon | Victoria | 3121 | Australia |
|
| Western Health | Recruiting | St Albans | Victoria | 3021 | Australia |
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| King Edward Memorial Hospital | Recruiting | Perth | Western Australia | 6008 | Australia |
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| The Mater Hospital | Recruiting | Brisbane | Australia |
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| Monash Health | Recruiting | Melbourne | Australia |
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| Peter MacCallum Centre | Recruiting | Melbourne | Australia |
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| Royal Womens Hospital | Recruiting | Melbourne | Australia |
|
| Medical University of Graz | Recruiting | Graz | Austria |
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| Hopital Universitaire Bruxelles | Recruiting | Brussels | Belgium |
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| Universitair Ziekenhuis Leuven | Recruiting | Leuven | Belgium |
|
| AC Camargo Cancer Centre | Recruiting | São Paulo | Brazil |
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| Vancouver General Hospital | Recruiting | Vancouver | Canada |
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| Klinikum St. Marien Amberg | Not yet recruiting | Amberg | Germany |
|
| Evangelische Waldkrankenhaus Spandau Berlin | Recruiting | Berlin-Spandau | Germany |
|
| Klinikum Lippe Detmold | Not yet recruiting | Detmold | Germany |
|
| Evang. Kliniken Essen-Mitte | Recruiting | Essen | Germany |
|
| Cork University Hospital | Recruiting | Cork | Ireland |
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| Universita di Bologna | Recruiting | Bologna | Italy |
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| Humanitas San Pio X | Recruiting | Milan | Italy |
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| San Gerardo Hospital | Recruiting | Monza | Italy |
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| Gemelli Hospital | Recruiting | Rome | Italy |
|
| Instituto Nacional de Cancerología | Recruiting | Mexico City | Mexico |
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| Radboudumc | Recruiting | Nijmegen | Gelderland | Netherlands |
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| Maastricht University Medical Center | Recruiting | Maastricht | Limburg | Netherlands |
|
| Catharina Ziekenhuis | Recruiting | Eindhoven | North Brabant | 5623 EJ | Netherlands |
|
| Elisabeth-TweeSteden Ziekenhuis | Recruiting | Tilburg | North Brabant | Netherlands |
|
| Amsterdam University Medical Center | Recruiting | Amsterdam | Netherlands |
|
| Antoni van Leeuwenhoek | Recruiting | Amsterdam | Netherlands |
|
| Amphia | Recruiting | Breda | Netherlands |
|
| Medisch Spectrum Twente | Recruiting | Enschede | Netherlands |
|
| University Medical Center Groningen | Recruiting | Groningen | Netherlands |
|
| Medical Center Leeuwarden | Recruiting | Leeuwarden | Netherlands |
|
| Leiden University Medical Center | Recruiting | Leiden | Netherlands |
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| Erasmus Medical Center | Recruiting | Rotterdam | Netherlands |
|
| University Medical Center Utrecht | Recruiting | Utrecht | Netherlands |
|
| Maxima Medical Center | Recruiting | Veldhoven | Netherlands |
|
| Isala Klinieken | Recruiting | Zwolle | Netherlands |
|
| Akershus University Hospital | Active, not recruiting | Nordbyhagen | Norway |
| Oslo University Hospital | Recruiting | Oslo | Norway |
|
| Stavanger Uniersity Hospital | Recruiting | Stavanger | Norway |
|
| Gdynia Oncology Centre | Recruiting | Gdynia | Poland |
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| Bonifraterskie Centrum Medyczne | Recruiting | Katowice | Poland |
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| Medical University of Silesia | Recruiting | Katowice | Poland |
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| National Cancer Institute Warsaw | Recruiting | Warsaw | Poland |
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| Vall D'Hebron Barcelona | Recruiting | Barcelona | Spain |
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| Karolinksa Institutet | Recruiting | Stockholm | Sweden |
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| Hospital Británico | Recruiting | Montevideo | Uruguay |
|
| Steenbeek MP, van Bommel MHD, intHout J, Peterson CB, Simons M, Roes KCB, Kets M, Norquist BM, Swisher EM, Hermens RPMG; TUBA-WISP II consortium; Lu KH, de Hullu JA. TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol. Int J Gynecol Cancer. 2023 Jun 5;33(6):982-987. doi: 10.1136/ijgc-2023-004377. |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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