P-231 - All RAS mutation predict for poor clinical outcomes after metastasectomy in patients with metastatic colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter H. Osumi
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H. Osumi1, E. Shinozaki1, Y. Miki2, M. Ueno3, M. Suenaga1, K. Chin1, M. Ogura1, M. Ozaka1, S. Matsusaka1, T. Yamaguchi1, N. Mizunuma1, Y. Kumekawa1, A. Saiura1, S. Okumura1
  • 1Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku/JP
  • 2Cancer Institute, Koto-ku/JP
  • 3Japanese Foundation for Cancer Research, Koto-ku/JP

Abstract

Introduction

Gene mutation in EGFR pathway was not the only predictive factor used for anti EGFR inhibitor but also prognostic factor in CRC patients. There was some evidence of a relationship between clinical outcomes after curative resection for CRC and these mutations, however it is uncertain for metastasectomy CRC patients. The aim of this study is to validate the clinicopathologic characteristics, frequencies of each mutation and co-mutation, and clinical outcomes after metastasectomy in Japanese patients.

Methods

A total of 1053 patients with histopathologically confirmed CRC patients who performed surgery and 138 patients received metastasectomy were enrolled from February 2012 to October 2013. OS was defined from time to diagnosis of metastatic disease until time to death. RFS was defined from the time of complete surgical resection until first disease recurrence or death that occurred first.

KRAS exon 2 was analyzed by Luminex® assay and other mutations were analyzed by Mu-pack®. The prognostic value was including age, sex, location of primly tumor, pathology, distant metastasis, MSI, clinical stage, and gene mutations. All reported P-values were the result of two-sided tests, with P < 0.05 considered statistically significant. Prognostic factors showing p < 0.2 in the univariate analysis were included in the multivariate analysis.

Results

The frequency of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, PIK3CA mutation were 50.7% (70/138), 3.6% (5/138), 5.1% (7/138), 5.1% (7/138), 8.7% (12/138) respectively. And more the co-mutation of PIK3CA was identified in 7.2% (10/138) of All-RAS mutant cases and in 0%(0/138) of BRAF mutant cases, respectively.

With a median follow up of 84.1 months (57.2-NA) for survivor, 4 year OS rate was 65.6% for All RAS mutant mCRC, 81.3% for those with All RAS wild mCRC (p < 0.02). KRAS exon2 mutation or any gene mutation tended to be significant difference and BRAF or PIK3CA mutation only weren't significant difference.

Complete resection of metastases was performed 95.8% (132/138) in all patients. The median RFS was 10 months (95%CI: 8.3-12.5).

In univariate analysis for OS, All RAS mutation and gender were showed of statistically significant prognostic factors. And more in multivariate analysis for OS, All RAS mutation, KRAS exon2 mutation and liver metastasis were showed of statistically significant prognostic factor.

In univariate and multivariate analysis for RFS, all factors of gene mutation s weren't showed of statistically significant.

Conclusion

All RAS mutation in mCRC metastasectomy patients was associated with worse clinical outcomes. It is necessary to accurate more cases to validate whether BRAF or PIK3CA mutation have a poor prognosis or not.