Multicenter Evaluation of Decentralized Homologous Recombination Deficiency Testing for Enhanced Molecular Diagnosis of Ovarian Cancer

Assessment of homologous recombination deficiency (HRD) and tumor BRCA1/2 mutation status in high-grade serous ovarian carcinoma (HGSOC) is clinically relevant for treatment decisions and for identifying tumors that may benefit from poly(adenosine diphosphate–ribose) polymerase inhibitors. The Myriad MyChoice® CDx HRD (M-HRD) assay is an established clinically validated HRD testing platform that is performed as a send-out test. We conducted a multicenter pilot study to assess the analytical feasibility and interlaboratory agreement of decentralized testing using the SOPHiA DDM™ Dx HRD Solution (SG-HRD). Three hospitals each contributed eight clinical HGSOC samples previously tested with M-HRD or with SG-HRD in a send-out platform. All centers independently prepared SG-HRD libraries and sequenced the complete set of 24 samples. Agreement with M-HRD was evaluated separately from comparisons with previous SG-HRD send-out results. Among specimens with interpretable M-HRD, overall percent agreement with local SG-HRD results was 95.0% (19/20), 90.0% (18/20), and 88.9% (16/18) at the three hospitals. BRCA1/2 variant calls were concordant with previous testing. Overall, the comparison with previous analyses by Myriad genetics or with previous SOPHiA GENETICS send-out results showed a high level of agreement, with discordances mainly observed in samples with values close to the classification threshold. The small, selected cohort, limited clinical replication, and absence of treatment-outcome assessment restrict precision estimates, generalizability, and conclusions regarding clinical validity. These findings support the analytical feasibility of decentralized SG-HRD testing, but larger studies are needed to characterize performance across a broader range of specimens and testing conditions.