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Homologous Recombination Deficiency (HRD) testing has been available for all NHS patients with newly diagnosed, advanced high-grade epithelial ovarian cancer to determine eligibility for PARP inhibitors Olaparib/Bevacizumab as an option for maintenance treatment. HRD status is determined by combining BRCA1/2 mutation status and a genomic instability score (GIS). Patients with HRD-positive tumours show an increased sensitivity to PARP inhibitors leading to significant improvements in progression-free survival. HRD referrals were previously sent to Myriad, but from April 2024 testing will be taken over by NHS England at each NHS Genomic Laboratory Hub (GLH). The Royal Marsden, as part of NT-GLH, surveyed wet-lab and bioinformatic solutions in a product evaluation for the replacement of this service. 23 FFPE samples were assessed across four assays, including GIS positive/negative and tBRCA positive/negative clinical cases and compared to the original reported results. Following a product performance review, two bioinformatic solutions were tested with a larger dataset of 59 FFPE samples before a final decision was made on the solution for routine service. The NT-GLH selected The SOPHiA DDM™ solution, which utilises low amplification WGS in conjunction with a deep learning algorithm called GIInger™ to produce a Genomic Integrity Index (GII). The GII is then paired with the Royal Marsden's in-house somatic DNA NGS panel (RMH200, Roche) to generate tBRCA status for a complete HRD status. The validation of the GIInger pipeline showed 88% overall percentage agreement (OPA) to previously reported samples (Myriad, AZ), increasing to 97.7% when samples +/- 10% of positivity threshold were excluded. The pipeline reproducibility and repeatability exhibited 100% concordance. The SOPHiA GIInger bioinformatics Pipeline for GI status, alongside our in-house RMH200 panel for tBRCA status provides a suitable HRD solution for testing patients with newly diagnosed, advanced high-grade epithelial ovarian cancer to determine PARP inhibitor eligibility. The pipeline was implemented at The Royal Marsden in December 2023, with 73 samples tested internally by March 2024.
Ratsma et al. (Sat,) studied this question.