KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: A study from the International Genetic Consortium for Liver Metastases Journal Article


Authors: Margonis, G. A.; Amini, N.; Andreatos, N.; Sasaki, K.; McVey, J.; Mirza, M. B.; Warner, S.; Buettner, S.; Barbon, C.; Wang, J.; Pulvirenti, A.; Angelou, A.; Kamphues, C.; Antoniou, E.; Pikoulis, E.; Pawlik, T. M.; Kaczirek, K.; Poultsides, G.; Wagner, D.; Endo, I.; Imai, K.; Aucejo, F.; Kreis, M. E.; Wolfgang, C. L.; Weiss, M. J.
Article Title: KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: A study from the International Genetic Consortium for Liver Metastases
Abstract: Background: 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. Methods: 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. Results: 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). Conclusions: 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. © 2019 International Hepato-Pancreato-Biliary Association Inc.
Keywords: adult; cancer chemotherapy; treatment response; aged; gene mutation; major clinical study; bevacizumab; disease association; multiple cycle treatment; cohort analysis; genetic association; prediction; irinotecan; preoperative period; liver resection; oncogene k ras; codon; oxaliplatin; colorectal liver metastasis; human; male; female; article
Journal Title: HPB
Volume: 21
Issue: 11
ISSN: 1365-182X
Publisher: Elsevier Science, Inc.  
Date Published: 2019-11-01
Start Page: 1527
End Page: 1534
Language: English
DOI: 10.1016/j.hpb.2019.03.368
PUBMED: 30979646
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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