Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis
Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis
复制标题
DOI：
10.1016/j.eururo.2017.09.011
复制
发表时间：
2018-04-01
期刊：
影响因子：
23.4
通讯作者：
Dyrskjot, Lars
中科院分区：
文献类型：
--
作者：
Birkenkamp-Demtroder, Karin;Christensen, Emil;Dyrskjot, Lars
在接受根治性膀胱炎的患者中，20-80%经历复发。迫切需要早期检测转移复发后的cysteine和监测正在进行的治疗的微创方法，以改善个性化的后续行动和治疗。因此，我们评估了血浆和尿液中循环肿瘤DNA（ctDNA）的使用，以检测cytoplasmic后的转移性复发并测量治疗效果。我们对肌层浸润性膀胱癌患者的肿瘤和生殖系DNA进行了外显子组测序，并通过针对61个基因的84个个性化数字液滴聚合酶链反应检测，在整个疾病过程中监测了370个液体活检组织中的ctDNA。患者在2013年至2017年期间前瞻性招募。与无疾病患者相比，转移性复发患者具有显著更高的ctDNA水平（p < 0.001）。从血浆ctDNA检测到确诊复发的中位时间为101 d（0-932 d）。使用液体活检转移复发和治疗反应的早期检测代表了一种新的，高度敏感的工具，用于监测患者，支持临床医生，并指导治疗decisions.Patient摘要：测量血浆和尿液中的肿瘤特异性突变可能是一个强大的工具，以监测治疗过程中的反应，并确定转移性疾病的早期体征。(c)2017年欧洲泌尿外科协会。由Elsevier B出版。V.保留所有权利。
Of the patients undergoing radical cystectomy, 20-80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p < 0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapsewas 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions.Patient summary: Measurement of tumour-specific mutations in plasma and urine may be a powerful tool to monitor response during treatment and identify early signs of metastatic disease.(c) 2017 European Association of Urology. Published by Elsevier B. V. All rights reserved.