Despite major advances in the treatment of metastatic colorectal cancer (mCRC), the survival rate remains very poor. This study aims at exploring the prognostic value of RAS-mutant allele fraction (MAF) in plasma in mCRC. Forty-seven plasma samples from 37 RAS-mutated patients with nonresectable metastases were tested for RAS in circulating tumor DNA using BEAMing before first- and/or second-line treatment. RAS MAF was correlated with several clinical parameters (number of metastatic sites, hepatic volume, carcinoembryonic antigen, CA19-9 levels, primary site location, and treatment line) and clinical outcome [progression-free survival (PFS) and overall survival (OS)]. An independent cohort of 32 patients from the CAPRI-GOIM trial was assessed for clinical outcome based on plasma baseline MAF. RAS MAF analysis at baseline revealed a significant correlation with longer OS [Hazard ratios (HR) = 3.514; P = 0.00066]. Patients with lower MAF also showed a tendency to longer PFS, although not statistically significant. Multivariate analysis showed RAS MAFs as an independent prognostic factor in both OS (HR = 2.73; P = 0.006) and first-line PFS (HR = 3.74; P = 0.049). Tumor response to treatment in patients with higher MAF was progression disease (P = 0.007). Patients with low MAFs at baseline in the CAPRI-GOIM group also showed better OS [HR = 3.84; 95% confidence intervals (CI) 1.5-9.6; P = 0.004] and better PFS (HR = 2.5; 95% CI: 1.07-5.62; P = 0.033). This minimally invasive test may help in adding an independent factor to better estimate outcomes before initiating treatment. Further prospective studies using MAF as a stratification factor could further validate its utility in clinical practice.

中文翻译：

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循环肿瘤DNA突变等位基因片段对RAS突变转移性结直肠癌预后的影响。

尽管在转移性结直肠癌（mCRC）的治疗方面取得了重大进展，但存活率仍然很差。本研究旨在探讨RAS突变等位基因片段（MAF）在血浆中对mCRC的预后价值。在第一线和/或第二线治疗之前，使用BEAMing对来自37位RAS突变且不可切除转移的患者的47份血浆样品进行了循环肿瘤DNA中的RAS检测。RAS MAF与几个临床参数（转移部位的数目，肝体积，癌胚抗原，CA19-9水平，主要部位的位置和治疗线）和临床结果[无进展生存期（PFS）和总体生存期（OS）相关]。来自CAPRI-GOIM试验的32名患者的独立队列根据血浆基线MAF评估了临床结局。基线的RAS MAF分析显示与更长的OS有显着相关性[危险比（HR）= 3.514; P = 0.00066]。MAF较低的患者也表现出PFS较长的趋势，尽管在统计学上不显着。多变量分析表明，RAS MAFs是OS（HR = 2.73; P = 0.006）和一线PFS（HR = 3.74; P = 0.049）的独立预后因素。MAF较高的患者对治疗的肿瘤反应为疾病进展（P = 0.007）。CAPRI-GOIM组基线时MAF低的患者也显示出更好的OS [HR = 3.84；95％置信区间（CI）1.5-9.6；P = 0.004]和更好的PFS（HR = 2.5； 95％CI：1.07-5.62； P = 0.033）。这种微创性测试可能有助于增加独立因素，以便在开始治疗之前更好地评估结果。