Schwaederle Maria, Chattopadhyay Ranajoy, Kato Shumei, Fanta Paul T, Banks Kimberly C, Choi In Sil, Piccioni David E, Ikeda Sadakatsu, Talasaz AmirAli, Lanman Richard B, Bazhenova Lyudmila, Kurzrock Razelle
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
Guardant Health, Inc., Redwood City, California.
Cancer Res. 2017 Oct 1;77(19):5419-5427. doi: 10.1158/0008-5472.CAN-17-0885. Epub 2017 Aug 14.
Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [ = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in (32.5% of patients), (13%), (12.5%), and (9.1%); for characterized alterations, 30.7% (), 7.6% (), 12.2% (), and 7.7% (). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis ( = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. .
通过对血液中循环肿瘤DNA（ctDNA）进行新一代测序（NGS），可能实现肿瘤的非侵入性基因组分析，但尚未有在大量不同癌症患者队列中的概念验证报告。在此，我们报告了对670例不同癌症患者血浆来源的ctDNA的分析结果。患者队列中所代表的肿瘤主要为胃肠道肿瘤（31.8%）、脑肿瘤（22.7%）或肺癌（20.7%）。从大多数患者[ = 423例（63%）]获得的ctDNA显示至少有一处改变。所观察到的最常见改变，以特征性突变或意义不明的变异形式出现，发生在 （32.5%的患者）、 （13%）、 （12.5%）和 （9.1%）；对于特征性改变，分别为30.7%（）、7.6%（）、12.2%（）和7.7%（）。我们发现32%的脑肿瘤至少有一处ctDNA改变。在多变量分析中，头颈部肿瘤与更多的改变独立相关（ = 0.019）。值得注意的是，670例患者中有320例（48%）显示出可能具有可操作性的改变，其中241例患者可能是FDA批准药物进行标签内或标签外治疗的候选者。文中提供了一些利用所获信息改善特定患者治疗的临床实用性实例。我们的研究结果证明了通过ctDNA NGS进行肿瘤基因组分析的可行性和影响，极大地鼓励了对该技术在癌症管理精准医学应用方面进行更广泛的研究。
