Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

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.

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

Tumor molecular profiling

ELENA FOUNTZILAS, MD

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.

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

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

The time from ovarian cancer diagnosis to the date of death from any cause

The time from initiation of first-line chemotherapy to the first documented progression, death from any cause or last contact, whichever occurred first

Hellenic Cooperative Oncology Group

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Anti-Infective Agents

All Drugs and Chemicals

Formaldehyde

Patients with recurrent locally advanced, metastatic and/or high-grade operable prostate cancer and available formalin-fixed paraffin-embedded tumor tissue. Patients received treatment at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments of oncology. Tumor molecular profiling was performed.

Tumor molecular profiling was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic

The aim of the study was to evaluate the prevalence, the prognostic and predictive value of gene alterations in unselected patients with prostate cancer. Patients with histologically confirmed prostate cancer, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments, were included. The presence of gene alterations was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic.

Data on tumor molecular profiling of European patients with prostate cancer is limited. The aim of the study was to evaluate the prevalence, the prognostic and predictive value of gene alterations in unselected patients with prostate cancer. Patients with histologically confirmed prostate cancer, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments, were included. The presence of gene alterations was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic. The primary endpoint was the prevalence of gene alterations in homologous recombination repair (HRR) genes. Secondary endpoint was overall survival.

FFPE tumor blocks from patients with recurrent locally advanced, metastatic and/or high-grade operable prostate cancer

Tumor Molecular Profiling in Patients With Prostate Cancer

Investigation of Mutations in DNA Damage Repair Genes and Other Actionable Molecular Aberrations as Biomarkers in Patients With Prostate Cancer

Time from diagnosis to the date of death, through the completion of the study

Number of patients with somatic mutations

NIPD Genetics

Symptoms and General Pathology

Recurrence

Elena Fountzila

We aim to employ targeted DNA NGS to evaluate the prevalence of germline and somatic mutations in cancer predisposing genes, such as BRCA1 and BRCA2, and other HR and DDR genes, including also a few additional clinically relevant genes, in patients with metastatic, locally advanced or high-grade prostate cancer. In addition, we will investigate the prognostic role of these mutations as well as their association with various clinicopathological parameters. This will be the first study investigating the prevalence of germline and somatic pathogenic mutations in Greek patients with prostate cancer.

This study will include formalin-fixed paraffin-embedded tumor tissue (FFPE) from 250 patients with metastatic, recurrent, locally advanced or "intermediate or high risk" (Gleason \>7), operable prostate cancer. FFPE tumor blocks alongside peripheral blood will be retrieved for all patients from Pathology Laboratories. Available FFPE blocks will be subjected to histological review by an experienced pathologist to evaluate H\&E sections for confirmation of diagnosis, histologic type, grade and tumor cell content (TCC%), as well as mark tumor dense areas for manual macro-dissection, prior to DNA extraction, in order to enrich samples for tumor DNA. Clinicopathologic characteristics of patients with prostate cancer will be retrieved from their respective medical records. Diagnosis will be confirmed through pathology reports, which will also provide information about Gleason Score and histological subtype.

In all instances, the collection of patient information will be in compliance with the regulations of the Bioethics committees of participating Hospitals. The study will be conducted in accordance with the principles of the Helsinki Declaration of Human Rights.

Following manual macro-dissection, FFPE tumor tissue material will be processed for DNA extraction, according to standard procedures with the QIAamp DNA Mini Kit (Qiagen GmbH, Hilden, Germany).

Sequencing will be performed at the Laboratory of Molecular Oncology, using an Ion Torrent Proton Sequencer (Life Technologies/Ion Torrent). For the purpose of targeted NGS genotyping of tumor and available matched germline DNA samples, we designed a custom Ampliseq panel to target coding relevant regions of genes involved in homologous recombination (HR), along with several others.

Data retrieval and base calling will be performed on the Torrent Server (v5.8.0.8). Consequently, we will then employ appropriate Ion Reporter Workflows (version 5.10) to automatically annotate single nucleotide variants (SNVs), multiple nucleotide variants (MNVs), small insertions / deletions (INDELs) and copy number variations (CNVs).

Formalin-fixed paraffin-embedded tissue samples and germline DNA

Molecular Profiling in Prostate Cancer

Prognostic and Predictive Value of Tumor Molecular Alterations in Patients With Prostate Cancer

Number of patients with either germline or somatic mutations

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer	NCT04716374	Epithelial Ovar...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Molecular Profiling in Prostate Cancer	NCT04983628	Prostate Cancer... Prostate Cancer... Germline BRCA1 ... Germline BRCA2 ... Mutation	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group

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