动态ctDNA监测指南 在接受新辅助化疗的局部晚期直肠癌患者的早期治疗强化.
Yu Shen1, Mingtian Wei1, Yazhou He2
1West China Hospital of Sichuan University Chengdu China.
概括
动态循环瘤DNA (ctDNA) 监测可以预测治疗初期局部晚期直肠癌 (LARC) 患者对新辅助化疗的反应不佳. 这种工具有助于识别需要替代疗法的患者,以获得更好的结果.
科学领域:
- 在瘤学瘤学.
- 分子诊断学 分子诊断
- 结直肠癌研究 结直肠癌研究
背景情况:
- 新辅助化疗 (NCT) 是局部晚期直肠癌 (LARC) 的标准.
- 预测NCT的病理反应是非常重要的,因为患者的结果是可变的.
- 早期识别不响应者是治疗适应所需的.
研究的目的:
- 评估动态循环瘤DNA (ctDNA) 分析,用于对接受NCT的LARC患者的早期反应监测.
- 确定ctDNA动力学是否可以预测病理反应和临床结果.
- 评估ctDNA作为治疗分层的生物标志物.
主要方法:
- 多中心随机化COPEC试验的生物标记子研究,涉及153名LARC患者.
- 在NCT期间进行序列血样本采集 (n=526) 进行瘤告知ctDNA测序.
- 将患者分为高风险 (延迟/没有清除,复发阳性) 和低风险 (早期清除,持续阴性) ctDNA动态组.
- ctDNA状态与病态瘤回归度 (pTRG) 和远程转移的相关性.
主要成果:
- 高风险的ctDNA动态与不良的病理反应 (pTRG3) 和远程转移 (59.4%对12.4%,p<0.001) 强烈相关.
- 动态ctDNA状态是反应不良的独立预测因素 (OR=11.69,p<0.001).
- 延迟/没有清除和复发的ctDNA阳性是显著的风险因素;单个手术前的ctDNA阳性结果也预测了反应不佳.
结论:
- 动态ctDNA监测有效地识别了LARC患者高风险的NCT失败早在两个周期.
- 这种方法可以指导适应性试验设计LARC治疗.
- 在LARC中,ctDNA分析为个性化治疗选择提供了一条途径.
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