Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort
Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort
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DOI：
10.21037/tlcr.2020.03.17
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发表时间：
2020-04-01
影响因子：
4
通讯作者：
Lu, Shun
中科院分区：
文献类型：
--
作者：
Song, Yong;Hu, Chengping;Lu, Shun
背景资料：尽管某些克隆的生长优势最终会转化为临床可见的疾病进展，但放射成像不能反映分子水平的克隆进化。循环肿瘤DNA（ctDNA）作为肺癌突变检测的工具，可以反映动态分子变化。我们评估了ctDNA作为预测和预后标志物在晚期非小细胞肺癌（NSCLC）patients.Methods疾病监测中的效用：这是一项多中心前瞻性队列研究。我们利用由949例具有驱动突变的晚期NSCLC患者的168个NSCLC相关基因组成的组对纵向血浆样本进行基于捕获的超深度测序，以监测治疗反应和疾病进展。对248例接受各种治疗的患者进行ctDNA与无进展生存期（PFS）/总生存期（OS）之间的相关性，至少进行2次ctDNA检测。这项研究的结果表明，较高的ctDNA丰度，（P=0.012）和突变计数（P=8.5x10（-4））与较短的OS相关。我们还发现，ctDNA清除的患者，不仅仅是驱动突变清除，在治疗过程中的任何时间点，与PFS较长相关（P=2.2x10（-1\f25 6，HR 0.28）和OS（P=4.5x10（-6），HR 0.19），与治疗类型和评估时间表无关。这个未来的真实的-一项全球性研究表明，治疗期间的ctDNA清除率可作为多种治疗方案的预测和预后标志物。
Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens.