前瞻性 RAXO 研究中，转移性结直肠癌的 RAS 和 BRAF 状态与可切除性、转化、转移灶切除术和预后的关系。

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study.

机构信息

Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

出版信息

Br J Cancer. 2022 Sep;127(4):686-694. doi: 10.1038/s41416-022-01858-8. Epub 2022 May 24.

DOI:10.1038/s41416-022-01858-8

PMID:35610367

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9381729/

Abstract

BACKGROUND

Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied.

METHODS

This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status.

RESULTS

Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups.

CONCLUSIONS

There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status.

CLINICAL TRIAL REGISTRATION

NCT01531621/EudraCT2011-003158-24.

摘要

背景

转移性结直肠癌（mCRC）患者接受转移灶切除术的预后与 RAS 和 BRAF 基因突变状态有关，但这些因素对可切除性和转化率的影响尚未得到广泛研究。

方法

这项前瞻性 RAXO 试验的子研究纳入了 2011 年至 2018 年期间招募的 906 例患者。我们根据 RAS 和 BRAF 状态评估了重复的中央可切除性评估、转化率/切除率和总生存期（OS）。

结果

患者包括 289 例 RAS 和 BRAF 野生型（RAS 和 BRAFwt）、529 例 RAS 突变型（RASmt）和 88 例 BRAF 突变型（BRAFmt）mCRC。转移灶的流行率在 RAS 和 BRAFwt/RASmt/BRAFmt 组之间有所不同，分别为肝脏（78%/74%/61%）、肺（24%/35%/28%）和腹膜（15%/15%/32%）转移灶。RASa 和 BRAFwt/RASmt/BRAFmt 患者的初始可切除性（32%/29%/15%）、转化率（16%/13%/7%）和切除/局部消融治疗（LAT）率（45%/37%/17%）不同。接受切除/LAT 治疗（n=342）的患者的中位 OS 为 83/69/30 个月，5 年 OS 率分别为 67%/60%/24%，而仅接受系统治疗（n=564）的患者的 OS 为 29/21/15 个月，5 年 OS 率分别为 11%/6%/2%在 RAS 和 BRAFwt/RASmt/BRAFmt 中。在所有亚组中，切除/LAT 均与 OS 改善相关。