Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands.
Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands.
Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):394-403. doi: 10.1016/j.bbcan.2017.08.002. Epub 2017 Aug 8.
The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract.
PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed.
A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n=10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15-3.22, p=0.01).
The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.
最近，检测血液中肿瘤来源突变（即循环肿瘤 DNA，ctDNA）的技术可能性不断扩大，这使得人们对液体活检的兴趣迅速增加。本综述和荟萃分析探讨了 ctDNA 在上消化道恶性肿瘤中的临床价值。
检索 PubMed、Cochrane 和 Embase 数据库，以确定报告 ctDNA 在食管癌、胃癌和胰腺癌患者中诊断、预后或预测价值的研究，检索时间截至 2017 年 1 月。使用随机效应两两荟萃分析评估 ctDNA 的诊断准确性和预后价值。
共有 34 项研究符合纳入标准。对于食管癌和胃癌，血液中癌基因的扩增，如 HER2 和 MYC，可能与诊断目的相关，并可预测某些患者亚群的治疗反应。鉴于评估 ctDNA 在食管癌和胃癌中作用的研究数量有限，荟萃分析仅评估了 ctDNA 在胰腺癌中的诊断准确性和预测价值（n=10）。ctDNA 作为诊断工具在胰腺癌中的总体敏感性和特异性分别为 28%和 95%。与 ctDNA 不可检测的患者相比，可检测到 ctDNA 的胰腺癌患者的总生存期较差（HR 1.92，95%置信区间（CI）1.15-3.22，p=0.01）。
ctDNA 的存在与胰腺癌患者的预后不良显著相关。尽管需要标准化测序技术并进一步开发高灵敏度检测方法，但 ctDNA 在临床实践中的应用具有广阔前景。
