Concordance between Three Homologous Recombination Deficiency (HRD) Assays in Patients with High-Grade Epithelial Ovarian Cancer

Elena Fountzilas^{1

2}, Kyriaki Papadopoulou³, Thomas Chatzikonstantinou⁴, Georgios Karakatsoulis⁴, Pantelis Constantoulakis⁵, Aikaterini Tsantikidi⁶, Georgios Tsaousis⁶, Sofia Karageorgopoulou⁷, Anna Koumarianou⁸, Davide Mauri⁹, Anastasios Ntavatzikos⁸, Zacharenia Saridaki^{10

11}, Georgios Petrakis¹², Florentia Fostira¹³, George Fountzilas^{14

15}, Michalis Liontos¹⁶

Affiliations

¹ Department of Medical Oncology, St. Lukes's Hospital, 55236 Thessaloniki, Greece.
² Medical Oncology, German Oncology Center, European University Cyprus, 1516 Nicosia, Cyprus.
³ Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, Greece.
⁴ Institute of Applied Biosciences, Centre for Research and Technology Hellas, 57001 Thessaloniki, Greece.
⁵ Genotypos M.S.A., 11528 Athens, Greece.
⁶ Genekor Medical S.A., 15344 Athens, Greece.
⁷ Third Department of Medical Oncology, IASO Clinic, 15123 Athens, Greece.
⁸ Hematology Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
⁹ Department of Medical Oncology, University Hospital of Ioannina, 45500 Ioannina, Greece.
¹⁰ 1st Oncology Department, Metropolitan Hospital, 18547 Athens, Greece.
¹¹ Oncology Department, "Asklepios DIAGNOSIS", 71303 Heraklion, Greece.
¹² Pathology Department, University General Hospital of Thessaloniki AHEPA, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
¹³ InRASTES, National Centre for Scientific Research "Demokritos", 15341 Athens, Greece.
¹⁴ Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
¹⁵ Department of Medical Oncology, German Oncology Center, 4108 Limassol, Cyprus.
¹⁶ Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

PMID: 38067228
PMCID: PMC10705222
DOI: 10.3390/cancers15235525

Concordance between Three Homologous Recombination Deficiency (HRD) Assays in Patients with High-Grade Epithelial Ovarian Cancer

Elena Fountzilas et al. Cancers (Basel). 2023.

. 2023 Nov 22;15(23):5525.

doi: 10.3390/cancers15235525.

Authors

Affiliations

¹ Department of Medical Oncology, St. Lukes's Hospital, 55236 Thessaloniki, Greece.
² Medical Oncology, German Oncology Center, European University Cyprus, 1516 Nicosia, Cyprus.
³ Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, Greece.
⁴ Institute of Applied Biosciences, Centre for Research and Technology Hellas, 57001 Thessaloniki, Greece.
⁵ Genotypos M.S.A., 11528 Athens, Greece.
⁶ Genekor Medical S.A., 15344 Athens, Greece.
⁷ Third Department of Medical Oncology, IASO Clinic, 15123 Athens, Greece.
⁸ Hematology Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
⁹ Department of Medical Oncology, University Hospital of Ioannina, 45500 Ioannina, Greece.
¹⁰ 1st Oncology Department, Metropolitan Hospital, 18547 Athens, Greece.
¹¹ Oncology Department, "Asklepios DIAGNOSIS", 71303 Heraklion, Greece.
¹² Pathology Department, University General Hospital of Thessaloniki AHEPA, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
¹³ InRASTES, National Centre for Scientific Research "Demokritos", 15341 Athens, Greece.
¹⁴ Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
¹⁵ Department of Medical Oncology, German Oncology Center, 4108 Limassol, Cyprus.
¹⁶ Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

PMID: 38067228
PMCID: PMC10705222
DOI: 10.3390/cancers15235525

Abstract

Our aim was to evaluate the concordance between the Myriad MyChoice and two alternative homologous recombination deficiency (HRD) assays (AmoyDx HRD Focus NGS Panel and OncoScan™) in patients with epithelial ovarian cancer (EOC). Tissue samples from 50 patients with newly diagnosed EOC and known Myriad MyChoice HRD status were included. DNA aliquots from tumor samples, previously evaluated with Myriad MyChoice and centrally reassessed, were distributed to laboratories to assess their HRD status using the two platforms, after being blinded for the Myriad MyChoice CDx HRD status. The primary endpoint was the concordance between Myriad MyChoice and each alternative assay. Tumor samples were evaluated with an AmoyDx^® HRD Focus Panel (n = 50) and with OncoScan™ (n = 43). Both platforms provided results for all tumors. Analysis showed that correlation was high for the Myriad MyChoice GI score and AmoyDx^® HRD Focus Panel (r = 0.79) or OncoScan™ (r = 0.87) (continuous variable). The overall percent agreement (OPA) between Myriad MyChoice GI status (categorical variable) and each alternative assay was 83.3% (68.6-93.3%) with AmoyDx and 77.5% (61.5-89.2%) with OncoScan™. The OPA in HRD status between Myriad MyChoice and AmoyDx was 88.6% (75.4-96.2). False-positive rates were 31.6% (6/19) for AmoyDx GI status and 31.9% (7/22) for OncoScan™, while false-negative rates were 0% (0/28, AmoyDx) and 11.1% (2/18, OncoScan™) compared with the Myriad MyChoice GI status. While substantial concordance between Myriad MyChoice and alternative assays was demonstrated, prospective validation of the analytical performance and clinical relevance of these assays is warranted.

Keywords: biomarker; concordance; enomic instability; epithelial ovarian cancer; homologous recombination deficiency.

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Conflict of interest statement

E.F.: Advisory role: LEO Pharma. Speaker fees: Roche, Pfizer, AstraZeneca. Stock ownership: Genprex Inc., Deciphera Pharmaceuticals Inc. Travel grant: Merck, Pfizer, K.A.M Oncology/Hematology and DEMO. SK: Consultation/Advisory: Astra Zeneca, Roche. Research: Novartis, Roche. Speaker: Astra Zeneca, Novartis, Roche. A.K.: Advisory role: Genesis Pharma. Honoraria: Pfizer. Speaker’s bureau: Roche. Research funding: Merck. Travel: MSD. Educational grants: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis and Ipsen. G.F.: Advisory Board: Pfizer, Novartis. Honoraria: AstraZeneca, Novartis. Stock ownership: Genprex Inc., Daiichi Sankyo, RFL Holdings, FORMYCON. M.L.: Employment: Pfizer. Stock and other ownership interests: Pfizer. Honoraria: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb/Celgene, Ipsen, Janssen, MSD Oncology, Roche, Sanofi. Consulting or advisory role: Amgen, AstraZeneca, GlaxoSmithKline, Janssen. Travel accommodations, expenses: AstraZeneca, Bayer, Pfizer, Roche; (I): Immediate Family Member. The rest of the authors declare no conflict of interest.

Figures

**Figure 1**
Correlation between Myriad MyChoice and each alternative homologous recombination deficiency (HRD) assay using genomic instability (GI) score. (A) Myriad MyChoice vs. AmoyDx^® HRD Focus Panel and (B) Myriad MyChoice vs. OncoScan™.

**Figure 2**
Areas under the curve for each HRD assay as predictor of Myriad MyChoice GI status: (A) AmoyDx^® HRD Focus Panel and (B) OncoScan™.

**Figure 3**
Progression-free survival (PFS) in patients with advanced-stage ovarian cancer. Solid blue line = PFS, Dashed black line = median PFS.

See this image and copyright information in PMC

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Concordance between Three Homologous Recombination Deficiency (HRD) Assays in Patients with High-Grade Epithelial Ovarian Cancer

Affiliations

Concordance between Three Homologous Recombination Deficiency (HRD) Assays in Patients with High-Grade Epithelial Ovarian Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources