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- Yoshikuni Kawaguchi, Scott Kopetz, Timothy E Newhook, Mario De Bellis, Yun Shin Chun, TzengChing-Wei DCDDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., ... more
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- Clin Cancer Res. 2019 Oct 1; 25 (19): 5843-5851.
PurposeSomatic 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 DesignWe 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.ResultsOf 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 = 0.858 and 0.729, respectively).ConclusionsRAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.©2019 American Association for Cancer Research.
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