Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases.
OBJECTIVE
While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown.


METHODS
A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses.


RESULTS
Median patient age was 58 years (IQR, 50.4-66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597).


CONCLUSIONS
KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. 2016;114:361-367. © 2016 Wiley Periodicals, Inc.
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Georgios Antonios
GA
Margonis
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Yuhree
Y
Kim
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Kazunari
K
Sasaki
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Mario
M
Samaha
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Stefan
S
Buettner
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Neda
N
Amini
Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
Timothy M
TM
Pawlik
D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018579:Patient Selection; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
CRLM; KRAS mutations; preoperative chemotherapy