A pilot study of evaluation of a deep-learning-based homologous recombination deficiency assay in korean patients with ovarian high-grade serous carcinoma: Diagnostic performance and clinical implications.

BACKGROUND

Homologous recombination deficiency (HRD)-related genetic mutations in ovarian high-grade serous carcinoma (HGSC) are known to be ethnic specific. Here, we assessed the diagnostic performance of HRD and its clinical implication in Korean HGSC patients using the SOPHiA DDM HRD Solution.

METHODS

Sixty-three ovarian cancer (OC) patients were enrolled, including 53 with HGSC and 10 with other subtypes. HRD status was determined by 28 homologous recombination repair (HRR) genetic sequencing and genomic scarring (GS) measurement. The GS was measured through low-pass whole-genome sequencing and quantified using the genomic integrity index (GII).

RESULTS

HRD status was analyzed in 53 out of 63 OC patients (84.1 %). Among the 53 with HGSC, HRD results were available for 83.0 % (n = 44). Of these HGSC patients, 72.7 % (n = 32) were HRD-positive, including 15 with BRCA1/2 mutations (34.1 %) and 27 with GI-positive (61.4 %). In HGSC, HRD-positive status was associated with solid, pseudoendometrioid or transitional (SET) pattern (P = 0.015). Patients with positive HRD and high GII (>4.2) exhibited improved disease-free survival (DFS) and overall survival (OS) compared to those with negative HRD (P = 0.003 and 0.024, respectively) and low GII (P < 0.001 and P = 0.006, respectively). Multivariate analysis revealed a high GII as a better prognostic indicator for DFS and OS (P = 0.003 and 0.032, respectively).

CONCLUSION

The HRD assay offers high diagnostic performance of HRD in Korean OC patients. Furthermore, the prognostic value of high GII and HRD, as well as an association with SET pattern and HRD was evident in HGSC.