TY - JOUR
T1 - Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases
T2 - Does the primary disease site matter?
AU - Amini, Neda
AU - Andreatos, Nikolaos
AU - Margonis, Georgios Antonios
AU - Buettner, Stefan
AU - Wang, Jaeyun
AU - Galjart, Boris
AU - Wagner, Doris
AU - Sasaki, Kazunari
AU - Angelou, Anastasios
AU - Sun, Jinger
AU - Kamphues, Carsten
AU - Beer, Andrea
AU - Morioka, Daisuke
AU - Løes, Inger Marie
AU - Antoniou, Efstathios
AU - Imai, Katsunori
AU - Pikoulis, Emmanouil
AU - He, Jin
AU - Kaczirek, Klaus
AU - Poultsides, George
AU - Verhoef, Cornelis
AU - Lønning, Per Eystein
AU - Endo, Itaru
AU - Baba, Hideo
AU - Kornprat, Peter
AU - NAucejo, Federico
AU - Kreis, Martin E.
AU - Christopher, Wolfgang L.
AU - Weiss, Matthew J.
AU - Safar, Bashar
AU - Burkhart, Richard Andrew
N1 - Publisher Copyright:
© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
PY - 2022/4
Y1 - 2022/4
N2 - Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. Conclusions: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
AB - Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. Conclusions: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
KW - KRAS mutation
KW - liver metastases
KW - rectal cancer
UR - http://www.scopus.com/inward/record.url?scp=85117339116&partnerID=8YFLogxK
U2 - 10.1002/jhbp.1054
DO - 10.1002/jhbp.1054
M3 - Article
C2 - 34614304
AN - SCOPUS:85117339116
SN - 1868-6974
VL - 29
SP - 417
EP - 427
JO - Journal of Hepato-Biliary-Pancreatic Sciences
JF - Journal of Hepato-Biliary-Pancreatic Sciences
IS - 4
ER -