HRD Score: A Promising Biomarker for Genomic Instability Evaluation for Targeted Treatments Among Pancreatic Cancer Patients.

IntroductionA subgroup of pancreatic cancer with unstable genome, such as BRCA mutation, may be more sensitive to platinum-based chemotherapy. How to define the patients with homologous recombination deficiency (HRD) status other than BRCA mutation has been a clinical challenge and interest.MethodsIn this retrospective cohort study, we collected NGS data of 163 pancreatic cancer patients from July 2020 to April 2024. HRD score was calculated by 3DMed-HRD algorithm. The median of HRD score of our study population was used as potential cut-off value to determine HRD status. Cox regression was used to evaluate association of HRD status, platinum-based chemotherapy and overall survival (OS). Kaplan-Meier method with log-rank test was performed to analyze OS among different subgroups.ResultsAmong the 163 patients, the HRD score ranged from 0 to 76. The mean value was 10.48. The median was 6. With a criterion of HRD ≥6 and/or germline Homologous Recombination Repair (HRR) mutation, a total of 89 patients were considered to be HRD+. HRD+ status was associated with a poor prognosis (HR: 1.46, 95%CI:1.01-2.11, p=0.04). Platinum-based all-time usage would reduce the hazard of death by 34% (HR: 0.66, 95%CI: 0.45-0.97, p=0.03). Among the HRD+ subjects, the initiation of platinum-based chemotherapy might be associated with a longer overall survival (OS: 19.92 vs 15.38, Log-Rank test, p=0.09).ConclusionHRD score could be a potential indicator for genome unstable pancreatic cancer patients who would benefit from platinum derivatives. Future study with better design and larger population size would help to determine a proper threshold for clinical application.