在转移性结直肠癌 (mCRC) 中，标准治疗方案期间可能会发生 RAS 突变丢失。在本研究中，我们旨在调查 RAS 基因的时间动态及其临床意义。这是一项回顾性、单中心研究，纳入了 82 名接受循环肿瘤 DNA 检测的组织 RAS 突变 (RAS-MT) mCRC 患者。 ctDNA）2013年1月至2023年4月期间的RAS监测。分析患者获得性RAS突变丢失（aRAS-ML）随时间的变化率和临床病理因素。评估了突变丢失的预后相关性。在 33 名 (40.2%) 患者中检测到 aRAS-ML，其中 32 名患者在第一次 ctDNA RAS 检测中出现突变丢失。第一次检测中检测到 RAS 突变的患者到第二次 ctDNA RAS 检测的中位时间为 8 个月，其中 4.5% 的病例新转化为 aRAS-ML；在第三次测定中没有检测到新的转化。在 ctDNA 测量过程中，aRAS-ML 组在靶器官中表现出更多的单器官转移（aRAS-ML：84.8% vs. RAS-MT：59.2%，p = 0.02）。在 33 名 aRAS-ML 患者中，7 名 (21.2%) 接受了抗表皮生长因子受体 (EGFR) 治疗，中位无进展生存期为 8 个月。多变量分析显示，持续性ctDNA RAS突变是总生存的独立预后因素（风险比：2.7，95%置信区间：1.1-6.3，p = 0.02）。RAS-MT mCRC患者ctDNA突变丢失率下降随着时间的推移。因此，在治疗早期使用 ctDNA RAS 检测将有助于挑战 EGFR 方案的使用。© 2024。作者。

In metastatic colorectal cancer (mCRC), RAS mutation loss may occur during the standard-of-care regimen. In this study, we aimed to investigate the temporal dynamics of the RAS gene and its clinical significance.This was a retrospective, single-center study that included 82 patients with tissue RAS-mutant (RAS-MT) mCRC who underwent circulating tumor DNA (ctDNA) RAS monitoring between January, 2013-April, 2023. Patients were analyzed for the rate of change over time to acquired RAS mutation loss (aRAS-ML) and clinicopathological factors. The prognostic relevance of mutation loss was assessed.aRAS-ML was detected in 33 (40.2%) patients, 32 of whom had a mutation loss in the first ctDNA RAS assay. Patients with a RAS mutation detected in the first assay had a median time of 8 months until the second ctDNA RAS assay, with 4.5% cases newly converted to aRAS-ML; no new conversions were detected at the third assay. The aRAS-ML group exhibited more single-organ metastases in the target organ during ctDNA measurement (aRAS-ML: 84.8% vs. RAS-MT: 59.2%, p = 0.02). Of the 33 patients with aRAS-ML, seven (21.2%) received anti-epidermal growth factor receptor (EGFR) therapy, with a median progression-free survival of 8 months. Multivariate analysis revealed that persistent ctDNA RAS mutation was an independent prognostic factor for overall survival (hazard ratio: 2.7, 95% confidence interval: 1.1-6.3, p = 0.02).The rate of ctDNA mutation loss in patients with RAS-MT mCRC decreases over time. Therefore, using a ctDNA RAS assay early in treatment will assist in challenging the use of EGFR regimens.© 2024. The Author(s).