Understanding Genomic Instability Score in Platinum-Treated Advanced Pancreatic Ductal Adenocarcinoma

Background/Objectives: First-line treatment selection for advanced (locally advanced or metastatic) pancreatic ductal adenocarcinoma (PDAC) is currently based on clinical characteristics rather than predictive biomarkers. While homologous recombination deficiency (HRD) is associated with increased sensitivity to platinum-based chemotherapy, established predictive biomarkers, such as pathogenic alterations in BRCA1, BRCA2, and PALB2, identify only a small subset of patients who are likely to benefit from platinum-based first-line treatment. The Genomic Instability Score (GIS) may capture broader HRD-associated genomic scarring beyond single-gene testing and support biomarker-guided platinum selection. However, the clinical utility of the GIS in PDAC remains uncertain, and no PDAC-specific GIS cutoff has yet been established.