Multicenter experience with large panel next-generation sequencing in patients with advanced solid cancers in Japan.
Multicenter experience with large panel next-generation sequencing in patients with advanced solid cancers in Japan.
复制标题
在日本对晚期实体癌患者进行大规模新一代测序的多中心经验。
DOI：
10.1093/jjco/hyy173
复制
发表时间：
2019
期刊：
影响因子：
2.4
通讯作者：
Saito T.
中科院分区：
文献类型：
--
作者：
Kato S;Hayashi T;Suehara Y;Hamanoue H;Yamanaka S;Ichikawa Y;Higurashi T;Ohashi K;Yamaguchi S;Nozaki Y;Terao Y;Saito T.
背景下一代DNA测序（NGS）技术近年来在世界多个国家的临床肿瘤学领域的应用越来越普遍。在日本，也正在逐步建立将NGS应用于常规临床实践的系统。在此过程中，我们在日本引进了肿瘤分析MSK-IMPACT（Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets）检测。方法我们在这里介绍了我们在2016年6月至2017年10月期间在日本两家机构选择的68名患者中使用MSK-IMPACT的初步经验。IMPACT测序是成功的，并在68例患者中的64例获得的标本中产生了结果，表示总体检测成功率为94.1%。检测的前三种癌症类型是子宫内膜癌（17.2%），胰腺癌（15.6%）和结直肠癌（12.5%）。遗传改变的临床可操作性评价显示，25.0%的患者（n= 16）具有至少一个可操作的改变。然而，在基因组匹配的临床试验中招募患者是困难的，主要是因为大多数临床试验仅限于来自特定器官/部位的肿瘤。一个病人的微卫星不稳定性高的状态，确定由MSK-IMPACT，与pembrolizumab治疗，并显示partial respons.ConclusionsAlthough肿瘤分析NGS和管理的基因组匹配治疗是一个很有前途的策略，因为它的成本高，我们需要考虑我们如何能适应它到日本的医疗系统。为此，我们认为分享我们在日本推进精准医疗的初步经验非常重要。
BackgroundApplication of next-generation DNA sequencing (NGS) has recently become increasingly common in the field of clinical oncology in several countries around the world. In Japan also, a system for applying NGS to routine clinical practice is gradually being established. During this process, we introduced in Japan the tumor-profiling MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) assay.MethodsWe present here our initial experience with the use of MSK-IMPACT in 68 patients selected from two institutions in Japan between June 2016 and October 2017.ResultsMSK-IMPACT sequencing was successful and yielded results in specimens obtained from 64 of the 68 patients, representing an overall assay success rate of 94.1%. The top three cancer types tested were endometrial cancer (17.2%), pancreatic cancer (15.6%) and colorectal cancer (12.5%). Evaluation of the clinical actionability of the genetic alterations revealed that 25.0% of patients (n= 16) harbored at least one actionable alteration. However, enrolling the patients in a genomically matched clinical trial was difficult, mainly because most clinical trials are limited to tumors arising from a specific organ/site. One patient with microsatellite instability-high status, as determined by MSK-IMPACT, was treated with pembrolizumab and showed partial response.ConclusionsAlthough tumor profiling by NGS and administration of genomically matched therapy is a promising strategy, because of its high cost, we need to consider how we can fit it into the Japanese medical system. Towards this end, we believe that it is important to share our initial experience for furthering precision medicine in Japan.