Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma

Abdelrahman Yousef(The University of Texas MD Anderson Cancer Center), Mahmoud Yousef(The University of Texas MD Anderson Cancer Center), Saikat Chowdhury(The University of Texas MD Anderson Cancer Center), Kawther Abdilleh(Pancreatic Cancer Action Network), Mark Knafl(The University of Texas MD Anderson Cancer Center), Paul Edelkamp(The University of Texas MD Anderson Cancer Center), Kristin Alfaro-Munoz(The University of Texas MD Anderson Cancer Center), Ray Chacko(The University of Texas MD Anderson Cancer Center), Jennifer Peterson(The University of Texas MD Anderson Cancer Center), Brandon G. Smaglo(The University of Texas MD Anderson Cancer Center), Robert A. Wolff(The University of Texas MD Anderson Cancer Center), Shubham Pant(The University of Texas MD Anderson Cancer Center), Michael S. Lee(The University of Texas MD Anderson Cancer Center), Jason Willis(The University of Texas MD Anderson Cancer Center), Michael J. Overman(The University of Texas MD Anderson Cancer Center), Sudheer Doss(Pancreatic Cancer Action Network), Lynn M. Matrisian(Pancreatic Cancer Action Network), Mark W. Hurd(The University of Texas MD Anderson Cancer Center), Rebecca A. Snyder(The University of Texas MD Anderson Cancer Center), Matthew H. G. Katz(The University of Texas MD Anderson Cancer Center), Huamin Wang(The University of Texas MD Anderson Cancer Center), Anirban Maitra(The University of Texas MD Anderson Cancer Center), John Paul Shen(The University of Texas MD Anderson Cancer Center), Dan Zhao(The University of Texas MD Anderson Cancer Center)
npj Precision Oncology
February 3, 2024
10.1038/s41698-024-00505-0
Cited by 79Open Access
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Abstract

Abstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic ( p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n = 408).

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