Impact of KRAS Mutations and Co-mutations on Clinical Outcomes in Pancreatic Ductal Adenocarcinoma

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation stat...

Descripción completa

Detalles Bibliográficos
Autores principales: Yousef, Abdelrahman, Yousef, Mahmoud, Chowdhury, Saikat, Abdilleh, Kawther, Knafl, Mark, Edelkamp, Paul, Alfaro-Munoz, Kristin, Chacko, Ray, Peterson, Jennifer, Smaglo, Brandon G., Wolff, Robert A., Pant, Shubham, Lee, Michael S., Willis, Jason, Overman, Michael, Doss, Sudheer, Matrisian, Lynn, Hurd, Mark W., Snyder, Rebecca, Katz, Matthew H.G., Wang, Huamin, Maitra, Anirban, Shen, John Paul, Zhao, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441514/
https://www.ncbi.nlm.nih.gov/pubmed/37609177
http://dx.doi.org/10.21203/rs.3.rs-3195257/v1
Descripción
Sumario:The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (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).

Ejemplares similares