ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Validation of the Clinical Use of GIScar, an Academic-developed Genomic Instability Score Predicting Sensitivity to Maintenance Olaparib for Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial.Nature communications · 2025Trial
- Homologous recombination deficiency (HRD) tests for ovarian cancer: a multicenter French phase II study (HERO).BMC cancer · 2025Trial
- Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Homologous recombination deficiency tumor tissue testing in a real-world cohort of tubo-ovarian carcinoma patients: validation of decentralized genomic profiling in 4777 cases.Virchows Archiv : an international journal of pathology · 2026Article
- Evaluation of homologous recombination testing in ovarian carcinoma.Virchows Archiv : an international journal of pathology · 2026Article
- Evaluation of the 1021-HRD assay compared to established HRD testing platforms in ovarian cancer.Translational oncology · 2026Article
- Integrative Genomic and Functional Analysis Reveals NF1 Loss as a Modifier of DNA Damage and Replication Stress Responses in Ovarian Cancer.Human mutation · 2026Article
- Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response.Journal of experimental & clinical cancer research : CR · 2025Article
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics.Biomarker research · 2025Review
- The PENDOR study: establishment of a panel of patient-derived tumor organoids from endometrial cancer to assess efficacy of PARP inhibitors.BMC cancer · 2025Observational
- Evaluation of the Oncomine Comprehensive Assay Plus NGS Panel and the OncoScan CNV Assay for Homologous Recombination Deficiency Detection.Molecular diagnosis & therapy · 2025Article
- Beyond HRD Status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer.Cancer research communications · 2024Article
- Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET.Biomolecules · 2024Article
- The OVAREX study: Establishment of ex vivo ovarian cancer models to validate innovative therapies and to identify predictive biomarkers.BMC cancer · 2024Observational
- Current HRD assays in ovarian cancer: differences, pitfalls, limitations, and novel approaches.Frontiers in oncology · 2024Review
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Authors and funding
27 authors at 13 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe optimal application of maintenance PARP inhibitor therapy for ovarian cancer requires accessible, robust, and rapid testing of homologous recombination deficiency (HRD). However, in many countries, access to HRD testing is problematic and the failure rate is high. We developed an academic HRD test to support treatment decision-making. EXPERIMENTAL
designGenomic Instability Scar (GIScar) was developed through targeted sequencing of a 127-gene panel to determine HRD status. GIScar was trained from a noninterventional study with 250 prospectively collected ovarian tumor samples. GIScar was validated on 469 DNA tumor samples from the PAOLA-1 trial evaluating maintenance olaparib for newly diagnosed ovarian cancer, and its predictive value was compared with Myriad Genetics MyChoice (MGMC).
resultsGIScar showed significant correlation with MGMC HRD classification (kappa statistics: 0.780). From PAOLA-1 samples, more HRD-positive tumors were identified by GIScar (258) than MGMC (242), with a lower proportion of inconclusive results (1% vs. 9%, respectively). The HRs for progression-free survival (PFS) with olaparib versus placebo were 0.45 [95% confidence interval (CI), 0.33-0.62] in GIScar-identified HRD-positive BRCA-mutated tumors, 0.50 (95% CI, 0.31-0.80) in HRD-positive BRCA-wild-type tumors, and 1.02 (95% CI, 0.74-1.40) in HRD-negative tumors. Tumors identified as HRD positive by GIScar but HRD negative by MGMC had better PFS with olaparib (HR, 0.23; 95% CI, 0.07-0.72).
conclusionsGIScar is a valuable diagnostic tool, reliably detecting HRD and predicting sensitivity to olaparib for ovarian cancer. GIScar showed high analytic concordance with MGMC test and fewer inconclusive results. GIScar is easily implemented into diagnostic laboratories with a rapid turnaround.
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