The KRAS G12D mutation increases the risk of unresectable recurrence of resectable colorectal liver-only metastasis

期刊论文
发表日期：

2024年7月31日

查看全文

Kai Chen,
Yukiyasu Okamura,
Keiichi Hatakeyama,
Akio Shiomi,
Hiroyasu Kagawa,
Hitoshi Hino,
Shoichi Manabe,
Yusuke Yamaoka,
Teiichi Sugiura,
Takashi Sugino,
Akifumi Notsu,
Takeshi Nagashima,
Keiichi Ohshima,
Kenichi Urakami,
Yasuto Akiyama,
Ken Yamaguchi

摘要

Purpose

Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM).

Methods

We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results.

Results

We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS.

Conclusions

This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.