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Specific Mutations in KRAS Codon 12 Associated With Poorer Overall Survival in Patients With Colorectal Liver Metastases

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Key Points

  • G12V and G12S mutations were associated with worse overall survival compared with wild-type tumors.
  • Among patients with recurrence after resection, G12V, G12C, and G12S mutations were associated with worse overall survival.

In a single-institution study reported in JAMA Surgery, Margonis et al found that particular KRAS codon 12 mutations were associated with significantly poorer overall survival among patients with colorectal liver metastases.

Study Details

This retrospective study included data from 331 patients who underwent resection for colorectal liver metastases at Johns Hopkins Hospital between 2003 and 2013. Overall, KRAS codon 12 and 13 mutations were detected in 91 patients (27.5%), including codon 12 mutations in 67 (20.2%) and codon 13 mutations in 24 (7.3%). Among patients with codon 12 mutations, the most common mutations were G12V (22 cases, 32.8%), G12D (25 cases, 37.3%), G12C (6 cases, 9.0%), G12S (7 cases, 10.4%), and G12A (4 cases, 6.0%). Among patients with codon 13 mutations, G13D was found in 23 cases (95.8%).

Association With Survival

During a median follow-up of 27.4 months, recurrence was observed in 48 patients with KRAS mutations (52.7%) and 130 patients (54.2%) with wild-type KRAS (P = .82). Median overall survival was 32.4 months in the mutation group vs 58.5 months in the wild-type group (P = .02), and 5-year survival was 32.7% vs 46.9%. Compared with the presence of wild-type KRAS, codon 12 mutations were associated with worse overall survival (hazard ratio [HR] = 1.54, P = .03), whereas the effect of codon 13 mutation was not significant (HR = 1.47, P = .19).

Among the six most common mutations, only codon 12 G12V (HR = 1.78, P = .05) and G12S (HR = 3.33, P = .02) were associated with worse overall survival compared with wild-type disease. Among patients with recurrence, G12V (HR = 2.96, P = .01), G12C (HR = 6.74, P = .002), and G12S mutations (HR = 4.91, P = .01) were associated with worse overall survival.

The investigators concluded, “G12V and G12S mutations of codon 12 were independent prognostic factors of worse [overall survival]. Among patients who recurred after resection of [colorectal liver metastases], G12V, G12C, and G12S mutations were associated with worse [overall survival]. Information on specific KRAS mutations may help individualize therapeutic and surveillance strategies for patients with resected [colorectal liver metastases].”

Timothy M. Pawlik, MD, MPH, PhD, of Johns Hopkins Hospital, is the corresponding author of the JAMA Surgery article.

The authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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