Dynamic Changes in Circulating Tumor DNA During Chemoradiation for Locally Advanced Lung Cancer
Dynamic Changes in Circulating Tumor DNA During Chemoradiation for Locally Advanced Lung Cancer
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DOI：
10.1016/j.adro.2019.05.004
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发表时间：
2019-10-01
影响因子：
2.3
通讯作者：
Nixon, Andrew B.
中科院分区：
文献类型：
--
作者：
Corradetti, Michael N.;Torok, Jordan A.;Nixon, Andrew B.
目的：同步放化疗是局部晚期肺癌的主要治疗方法。由于CRT导致的细胞死亡会导致无细胞DNA（cfDNA）和循环肿瘤DNA（ctDNA）释放到血液中，但人们对这一过程的动力学和特征知之甚少。我们假设，可能有临床意义的变化cfDNA和ctDNA.Methods和材料：多个样品的血浆从24例接受CRT治疗的局部晚期肺癌的平均剂量为66戈伊（范围，58-74戈伊）在以下时间间隔：CRT前，在CRT期间的第2周和第5周，治疗后6周。cfDNA进行定量，和一种新的下一代测序（NGS）技术，使用增强的标签/靶向扩增子测序进行分析ctDNA.Results：在基线时间点的ctDNA中的特定突变是不可检测的患者的生存率提高，并可能通过NGS在多个患者的CRT的整个过程中追踪病因驱动突变。我们定量了CRT前、治疗后第2周、第5周和第6周患者的cfDNA水平。在治疗的第2周和第5周没有观察到差异，但我们注意到治疗后随访样品中cfDNA与CRT前收集的样品相比显著增加（P = 0.05）。结论：在局部晚期肺癌患者的CRT的整个过程中观察到cfDNA和ctDNA的动态变化。可以使用NGS方法鉴定和追踪具有治疗意义的特定突变。需要进一步的工作来表征接受CRT治疗的患者中cfDNA和ctDNA随时间的变化，并评估这种强大技术的预测和预后潜力。(C)2019作者爱思唯尔公司出版代表美国放射肿瘤学会。
Purpose: Concurrent chemoradiation therapy (CRT) is the principal treatment modality for locally advanced lung cancer. Cell death due to CRT leads to the release of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) into the bloodstream, but the kinetics and characteristics of this process are poorly understood. We hypothesized that there could be clinically meaningful changes in cfDNA and ctDNA during a course of CRT for lung cancer.Methods and materials: Multiple samples of plasma were obtained from 24 patients treated with CRT for locally advanced lung cancer to a mean dose of 66 Gy (range, 58-74 Gy) at the following intervals: before CRT, at weeks 2 and 5 during CRT, and 6 weeks after treatment. cfDNA was quantified, and a novel next generation sequencing (NGS) technique using enhanced tagged/ targeted-amplicon sequencing was performed to analyze ctDNA.Results: Patients for whom specific mutations in ctDNA were undetectable at the baseline time point had improved survival, and potentially etiologic driver mutations could be tracked throughout the course of CRT via NGS in multiple patients. We quantified the levels of cfDNA from patients before CRT, at week 2, week 5, and at 6 weeks after treatment. No differences were observed at weeks 2 and 5 of therapy, but we noted a significant increase in cfDNA in the posttreatment followup samples compared with samples collected before CRT (P = .05).Conclusions: Dynamic changes in both cfDNA and ctDNA were observed throughout the course of CRT in patients with locally advanced lung cancer. Specific mutations with therapeutic implications can be identified and tracked using NGS methodologies. Further work is required to characterize the changes in cfDNA and ctDNA over time in patients treated with CRT and to assess the predictive and prognostic potential of this powerful technology. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.