TY - JOUR
T1 - Mutation status of Ras, TP53, and Smad4 is superior to mutation status of Ras alone for predicting prognosis after resection of colorectal liver metastases
AU - Kawaguchi, Yoshikuni
AU - Kopetz, Scott
AU - Newhook, Timothy E.
AU - De Bellis, Mario
AU - Chun, Yun Shin
AU - Tzeng, Ching Wei D.
AU - Aloia, Thomas A.
AU - Vauthey, Jean Nicolas
N1 - Funding Information:
The authors thank Dr. Elena Panettieri for reviewing the data used in the study, Ms. Ruth Haynes for administrative support in the preparation of this manuscript, and Ms. Stephanie Deming, an employee of the Department of Scientific Publications at MD Anderson Cancer Center, for copyediting the manuscript. This research was supported, in part, by the NIH through MD Anderson Cancer Center Support Grant, CA016672.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Purpose: Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection. Experimental Design: We identified patients who underwent initial CLM resection during 2007-2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models. Results: Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P ¼ 0.858 and 0.729, respectively). Conclusions: RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.
AB - Purpose: Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection. Experimental Design: We identified patients who underwent initial CLM resection during 2007-2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models. Results: Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P ¼ 0.858 and 0.729, respectively). Conclusions: RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.
UR - http://www.scopus.com/inward/record.url?scp=85069695345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069695345&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-0863
DO - 10.1158/1078-0432.CCR-19-0863
M3 - Article
C2 - 31221662
AN - SCOPUS:85069695345
SN - 1078-0432
VL - 25
SP - 5843
EP - 5851
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -