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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2021

01-02-2021 | Metastasis | Hepatobiliary Tumors

Association of RAS Mutation Location and Oncologic Outcomes After Resection of Colorectal Liver Metastases

Authors: Lily V. Saadat, MD, Thomas Boerner, MD, Debra A. Goldman, MS, Mithat Gonen, PhD, Timothy L. Frankel, MD, Efsevia Vakiani, MD, PhD, T. Peter Kingham, MD, William R. Jarnagin, MD, Alice C. Wei, MD, Kevin C. Soares, MD, David B. Solit, MD, Michael I. D’Angelica, MD

Published in: Annals of Surgical Oncology | Issue 2/2021

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Abstract

Background

RAS mutations are prognostic for patients with metastatic colorectal cancer (mCRC). We investigated clinical, pathologic, and survival differences based on RAS exon for patients with colorectal liver metastases (CRLM).

Methods

This retrospective, single-center study included patients with R0/R1 resection of CRLM from 1992 to 2016. Patients with unresected extrahepatic disease or liver-first resection were excluded. Overall survival (OS) and recurrence-free survival were assessed and stratified by mutation status and location. Fisher’s exact test, Wilcoxon rank-sum test, and log-rank test were used, where appropriate.

Results

A total of 938 mCRC patients were identified with median age of 57 (range 19–91). Of the 445 patients with KRAS mutations, 407 (91%) had a mutation in exon 2, 14 (3%) exon 3, and 24 (5%) exon 4. Median OS was 71.4 months (95% confidence interval [CI] 66.1–76.5). Patients with KRAS mutations had worse OS compared with KRAS wild-type patients (median 55.5 vs. 91.3 months, p < 0.001). While there was no significant difference in OS based on the exon mutated (p = 0.12), 5-year OS was higher for patients with exon 4 mutations [68.8% (95% CI 0.45–0.84)] compared with those with mutations in exon 2 [45.7% (95% CI 0.40–0.51)] or exon 3 [39.1% (95% CI: 0.11–0.68)]. Patients with NRAS mutant tumors also had worse OS compared with NRAS wild-type patients (median 50.9 vs. 73.3 months, p = 0.03).

Conclusions

NRAS and KRAS exon 3/4 mutations are present in a minority of mCRC patients. Patients with exon 4 mutant tumors may have a more favorable prognosis, although the difference in oncologic outcomes based on mutated exon appears to be smaller than previously reported.
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Metadata
Title
Association of RAS Mutation Location and Oncologic Outcomes After Resection of Colorectal Liver Metastases
Authors
Lily V. Saadat, MD
Thomas Boerner, MD
Debra A. Goldman, MS
Mithat Gonen, PhD
Timothy L. Frankel, MD
Efsevia Vakiani, MD, PhD
T. Peter Kingham, MD
William R. Jarnagin, MD
Alice C. Wei, MD
Kevin C. Soares, MD
David B. Solit, MD
Michael I. D’Angelica, MD
Publication date
01-02-2021
Publisher
Springer International Publishing
Keyword
Metastasis
Published in
Annals of Surgical Oncology / Issue 2/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08862-3

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