RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases

Abstract

Background

In patients undergoing resection of colorectal liver metastases (CLM), resection margin status is a significant predictor of survival, particularly in patients with suboptimal response to preoperative therapy. RAS mutations have been linked to more invasive and migratory tumor biology and poor response to modern chemotherapy.

Objective

The aim of this study was to evaluate the relationship between RAS mutation and resection margin status in patients undergoing resection of CLM.

Methods

Patients who underwent curative resection of CLM from 2005 to 2013 with known RAS mutation status were identified from a prospectively maintained database. A positive margin was defined as tumor cells <1 mm from the parenchymal transection line.

Results

The study included 633 patients, of whom 229 (36.2 %) had mutant RAS. The positive margin rate was 11.4 % (26/229) for mutant RAS and 5.4 % (22/404) for wild-type RAS (p = 0.007). In multivariate analysis, the only factors associated with a positive margin were RAS mutation (hazard ratio [HR] 2.439; p = 0.005) and carcinoembryonic antigen level 4.5 ng/mL or greater (HR 2.060; p = 0.026). Among patients presenting with liver-first recurrence during follow-up, those with mutant RAS had narrower margins at initial CLM resection (median 4 mm vs. 7 mm; p = 0.031). A positive margin (HR 3.360; p < 0.001) and RAS mutation (HR 1.629; p = 0.044) were independently associated with worse overall survival.

Conclusion

RAS mutations are associated with positive margins in patients undergoing resection of CLM. Tumors with RAS mutation should prompt careful efforts to achieve negative resection margins.

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Acknowledgment

The authors thank Stephanie Deming, an employee of the Department of Scientific Publications, MD Anderson Cancer Center, for copyediting the manuscript, and Ruth J. Haynes, an employee of the Department of Surgical Oncology, MD Anderson Cancer Center, for secretarial assistance in the preparation of the manuscript. This research was supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant, CA016672. Dr. Brudvik is supported by the Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway, and was awarded the Unger–Vetlesen Medical Fund for 2014. Dr Passot is supported by the French Association of Surgery (AFC).

Disclosure

Kristoffer Watten Brudvik, Yoshihiro Mise, Michael Hsiang Chung, Yun Shin Chun, Scott E. Kopetz, Guillaume Passot, Claudius Conrad, Dipen M. Maru, Thomas A. Aloia, and Jean-Nicolas Vauthey report no conflicts of interest relevant to this article.

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Correspondence to Jean-Nicolas Vauthey MD.

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Brudvik, K.W., Mise, Y., Chung, M.H. et al. RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases. Ann Surg Oncol 23, 2635–2643 (2016). https://doi.org/10.1245/s10434-016-5187-2

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Keywords

  • Resection Margin
  • Preoperative Chemotherapy
  • Positive Margin
  • Colorectal Liver Metastasis
  • Viable Tumor Cell