Background: KRAS mutation is present in over 90% of PDAC, one of the leading causes of cancer death in Australia and the world. This retrospective cohort study aims to investigate the role of detecting the KRAS mutation and subtype in PDAC patients to determine prognosis across all stages of disease.
Methods: We reviewed the records of 231 patients presenting with PDAC to a large tertiary hospital. We recorded age, sex, date of diagnosis, date of death, NCCN clinical stage, KRAS status, KRAS detection method and type of treatment received, and compared survival using the Kaplan Meier, log-rank test and Cox proportional hazards regression model.
Results: The 3 most frequently occurring KRAS mutation subtypes were G12D (40.3%), G12V (27.7%) and G12R (10.4%). KRAS mutation was not significantly associated with poorer survival compared to KRAS wild-type (HR 1.042, 95% 0.813 - 1.334; p=0.747) and G12D mutation subtype was not significantly associated with poorer survival compared to all other PDAC patients (HR 1.155, 95% CI 0.834 - 1.600; p=0.385). Within the operable group, G12D patients had a significantly shorter median survival time of 356 days compared to all other PDAC patients (median survival 869 days) (HR 2.081, 95% CI 1.063 - 4.076; p=0.033).
Discussion: There was no association between KRAS mutation and survival across all NCCN stages. G12D patients who were operable or received surgery had significantly shorter survival compared to all other PDAC patients. These data suggests that KRAS G12D may be a clinically useful prognostic biomarker in the future.