RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases

Ann Surg. 2019 Jan;269(1):120-126. doi: 10.1097/SLA.0000000000002319.

Abstract

Objective: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM).

Background: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS.

Methods: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients.

Results: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not.

Conclusions: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics*
  • Female
  • Follow-Up Studies
  • Hepatectomy*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Postoperative Period
  • Propensity Score*
  • Retrospective Studies
  • Survival Rate / trends
  • Tomography, X-Ray Computed
  • Ultrasonography
  • United States / epidemiology
  • ras Proteins / genetics*
  • ras Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • ras Proteins