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

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.