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RAS Mutation Status Impacts Survival in Patients Undergoing Repeat Hepatectomy for Colorectal Liver Metastases
Jason Denbo*1, Guillaume Passot1, Yun Shin Chun1, Suguru Yamashita1, Scott Kopetz2, Dipen Maru3, Kristoffer W. Brudvik1, Steven Wei1, Claudius Conrad1, Thomas Aloia1, Jean-Nicolas Vauthey1
1Surgical Oncology, MD Anderson, Houston, TX; 2Medical Oncology, MD Anderson Cancer Center, Houston, TX; 3Pathology, MD Anderson Cancer Center, Houston, TX
Background: Repeat hepatectomy for recurrent colorectal liver metastases (CLM) is safe and can provide long-term survival. In patients who undergo hepatectomy for CLM, RAS mutation status has been shown to impact recurrence and survival.
Objective: To evaluate the impact of RAS mutation status in patients undergoing repeat hepatectomy for CLM.
Methods: Identified all patients who underwent hepatectomy with known RAS mutation status for CLM between January 2005 and November 2014. Then, we compared the outcomes of patients who underwent repeat curative-intent hepatectomy with respect to their RAS mutation status, and performed multivariate analysis for predictors of recurrence free survival (RFS) and overall survival (OS).
Results: RAS mutation status was known for 922 patients who underwent hepatectomy. Ninety-nine of these patients underwent repeat hepatectomy, and 33 (33%) harbored a RAS mutation. The RAS wild type (WT) and mutant groups had similar clinicopathologic characteristics. Recurrence-free survival (RFS) was not different for RAS WT and mutant groups, 8.5 months and 7 months, respectively (p=0.683). Median overall survival (OS) was 62.5 months for the RAS WT group, compared to 39.3 months for the mutant group, (p=0.028). On multivariate regression analysis, only tumor size >3cm [hazard ratio (HR)=2.0, p=0.009] was associated with worse RFS, while RAS mutation (HR=2.0, p=0.046) and tumor size >3cm (HR=2.5, p=0.018) predicted worse OS, and major hepatectomy (HR=0.36, p=0.032) improved OS.
Conclusion: RAS mutations and large tumor size were associated with worse OS following repeat hepatectomy, thus consideration should be given to RAS mutation status preoperatively.
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