Defining the Grey Zone in Homologous Recombinant Testing in Ovarian Cancer – Using Bioinformatics to Determine Response to Precision Medicine

High-grade serous carcinoma (HGSC) patients that test positive for homologous recombinant deficiency (HRD), defined as those who have a Genomic Instability Score (GIS) of ≥ 42, are eligible for PARP-inhibitor (PARPi) therapy. These patients have longer average progression-free survival (PFS), but little is known about patients who have a GIS in this ‘grey zone’, defined as within 1-2 integers of the arbitrary 42 cut-off. In this project, patients with and HRD score within the grey zone had their GIS repeated multiple times to determine the test reproducibility.  Three patients were identified with HRD of 42 or 44. The data demonstrated variability within patient testing. In one patient, all 10 runs showed reproducible results while in another patient, with an initial HRD of 44, the NGS showed an HRD range between 38-45 from 9 runs even though the sample was taken from same tissue block and library preparation. Tumour content was not shown to be an independent factor. It is important to consider patient range for retesting. The data suggests a patient with a HRD score as low as 38 to as high as 45 could be considered for reassessment to ensure only patients that will see benefit receive a PARPi.