Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

Study Overview
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Brief Summary
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Molecular alterations in Homologous Recombination Repair (HRR) genes have been associated with clinical benefit from chemotherapy and/or Poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer. Therefore, the performance of tumor molecular profiling is currently recommended by international guidelines at initial diagnosis, among other reasons, for the modification of the treatment plan. The investigators' hypothesis was that tumor molecular profiling reveals additional parameters that can improve the predictive and prognostic role of the mere presence of HRR gene mutations. The study aimed to investigate the prognostic and predictive role of clonality of pathogenic variants in HRR genes and/or concurrent pathogenic variants in other clinically relevant genes.

Official Title
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Clonality of Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Other: Tumor molecular profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with epithelial ovarian cancer Received treatment at HeCOG-affiliated institutions Have signed informed consent With adequate tumor tissue for analysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with epithelial ovarian cancer<br>Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions following standard international guidelines. | Other: Tumor molecular profiling<br>* Tumor tissue processing and all NGS genotyping were performed at the Laboratory of Molecular Oncology (Hellenic Foundation for Cancer Research / AUTH). Paraffin H&E sections from the retrieved tissue blocks were centrally reviewed for tumor histology and tissue adequacy for DNA extraction and were marked for macrodissection along with tumor DNA content [(former tumor cell content (TCC%)] assessment. DNA was extracted from macrodissected tissue fragments with the QIAamp® DNA mini kit (Qiagen, Hilden, Germany), measured in a Qubit fluorometer (Thermo Fisher Scientific, Paisley, UK), and genotyped with NGS in an Ion Torrent Proton sequencer (Thermo Fisher Scientific) by using a previously published custom panel (Kotoula, Lakis et al. 2019). Following stringent variant quality filtering (Kotoula, Chatzopoulos et al. 2021), 500 tumors<br>* Other names: NGS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The time from ovarian cancer diagnosis to the date of death from any cause | Through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The time from initiation of first-line chemotherapy to the first documented progression, death from any cause or last contact, whichever occurred first | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epithelial ovarian cancer, Next Generation Sequencing (NGS), Pathogenic variants, Tumor molecular profiling, Clonality, Homologous recombination repair