Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Margonis, GA; Amini, N; Andreatos, N; Sasaki, K; McVey, J; Mirza, MB; Warner, S; Buettner, S; Barbon, C; Wang, J; Pulvirenti, A; Angelou, A; Kamphues, C; Antoniou, E; Pikoulis, E; Pawlik, TM; Kaczirek, K; Poultsides, G; Wagner, D; Endo, I; Imai, K; Aucejo, F; Kreis, ME; Wolfgang, CL; Weiss, MJ.
KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases.
HPB (Oxford). 2019; 21(11):1527-1534
Doi: 10.1016/j.hpb.2019.03.368
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- Co-Autor*innen der Med Uni Graz
- Wagner Doris
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- Abstract:
- A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined. Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response. 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P = 0.01) and wtKRAS status remained independently associated with a major response (P = 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P = 0.023). Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations. Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.