What we do
About our project
Aim of the Project
The goal of the Selecting Ovarian cancer patients for PARP Inhibitor (SOPI) study is to identify an accurate biomarker test for homologous recombination deficiency (HRD) in epithelial ovarian cancer (EOC). Currently, poly ADP-ribose polymerase inhibitors (PARP-i) are administered exclusively when a patient tests positive for HRD. Until now, no HRD test is selected as superior test to determine the HRD status of the tumor. The absence of a standardized test has the potential to introduce considerable variation and may lead to over- or under-treatment. Therefore, this projects aims to evaluate and select the most effective HRD test that predicts the longest progression-free survival (PFS) in non-BRCA EOC patients treated with PARP-i.Execution of the Project
The SOPI study will use a comprehensive approach, comparing three existing HRD tests in advanced stage EOC patients receiving standard care treatment, including cytoreductive surgery and platinum-based chemotherapy. The three tests are; the TSO500 HRD, the RECAP test, and the RAD51-FFPE test. Each test offers a perspective on HRD status of the tumor, and the study will determine which test correlates best with the progression free survival (PFS) in patients treated with maintenance therapy PARP-i.In the first part of the study, fresh tumor tissue will be collected from patients with suspected ovarian cancer, providing a valuable resource for the evaluation of HRD tests. The second part focuses on patients with proven advanced EOC who have received a positive HRD result from at least one of the three tests and will start with PARP-i treatment. Clinical data, Quality of Life assessments, and blood samples (opt-in) will be collected. And the PFS, overall survival, and treatment-related toxicities will be analyzed.
Molecular analysis
The TSO500 HRD test is a DNA based test that identifies specific genetic variants or abnormalities associated with HRD. The test is based on next-generation sequencing and the HRD score reflects the degree of genomic instability and the potential deficiency in homologous recombination repair.The RECAP-test, involves exposing extracted tumor tissue to radiation to induce DNA damage. Subsequently, the presence or absence of the RAD51 protein, vital for DNA damage repair, is visualized through immunofluorescence. Absence of RAD51 indicates that the tumor is HRD positive and therefore susceptibility to PARP-i.
The RAD51-FFPE test, is conducted directly on the tumor tissue embedded in paraffin. Using immunofluorescence, the presence or absence of the RAD51 protein is visualized, allowing for the determination of the HRD status.
Impact on Patient Care
The societal impact of the SOPI project is considerable. The successful identification of a reliable HRD test will revolutionize the selection of EOC patients eligible for PARP-i, ensuring that only those who are likely to benefit receive this treatment. This precision medicine approach not only protects patients from unnecessary side effects and burdensome hospital visits but also has significant economic implications. The SOPI study aims to enhance the cost-effectiveness of PARP-i therapy, improve patient outcomes, and contribute valuable insights to the field of personalized ovarian cancer treatment.Funds & Grants
This study is funded by KWF Kankerbestrijding (Dutch Cancer Society. project number 15374), and supported by the departments involved in the study.
Collaborations
Collaboration outside of the Erasmus MC
- LUMC, Maaike Vreeswijk, Associate Professor of Human Genetics
- UMCG, Dr. Hilde Jalving, Internist oncologist
- MUMC, Dr. Tonneke Beijers, Internist oncologist
- Albert Schweitzer hospital, Dr. Gatske Nieuwenhuyzen-de Boer, Gynaecological Oncologist
- Catharina hospital, Dr. Jurgen Piek, Gynaecological Oncologist
Collaboration within the Erasmus MC
- Department of Gynaeciological Oncology
- Department of Molecular genetics
- Department of Pathology
- Department of Oncology
Our Team
- Heleen van Beekhuizen, gynaecological oncologist
- Ingrid Boere, medical oncologist
- Merel Vegter, Phd-candidate,
- Marianne Maliepaard, research coordinator
- Gatske Nieuwenhuyzen - de Boer, gynaecological oncologist
- Dik van Gent, PI
- Erik-Jan Dubbink, molecular biologist
- Floris Groenendijk, Gynaecopathologist/clinical scientist in Molecular Pathology
- Ronnie van der Holt, statistician, Hematolgy
