TY - JOUR
T1 - KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy
T2 - a study from the International Genetic Consortium for Liver Metastases
AU - Margonis, Georgios A.
AU - Amini, Neda
AU - Andreatos, Nikolaos
AU - Sasaki, Kazunari
AU - McVey, Jack
AU - Mirza, Muhammad B.
AU - Warner, Samuel
AU - Buettner, Stefan
AU - Barbon, Carlotta
AU - Wang, Jane
AU - Pulvirenti, Alessandra
AU - Angelou, Anastasios
AU - Kamphues, Carsten
AU - Antoniou, Efstathios
AU - Pikoulis, Emmanouil
AU - Pawlik, Timothy M.
AU - Kaczirek, Klaus
AU - Poultsides, George
AU - Wagner, Doris
AU - Endo, Itaru
AU - Imai, Katsunori
AU - Aucejo, Federico
AU - Kreis, Martin E.
AU - Wolfgang, Christopher L.
AU - Weiss, Matthew J.
N1 - Publisher Copyright:
© 2019 International Hepato-Pancreato-Biliary Association Inc.
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85063998169&partnerID=8YFLogxK
U2 - 10.1016/j.hpb.2019.03.368
DO - 10.1016/j.hpb.2019.03.368
M3 - Article
C2 - 30979646
AN - SCOPUS:85063998169
SN - 1365-182X
VL - 21
SP - 1527
EP - 1534
JO - HPB
JF - HPB
IS - 11
ER -