Marrone Michael, Filipski Kelly K, Gillanders Elizabeth M, Schully Sheri D, Freedman Andrew N
Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Rockville, Maryland, USA.
PLoS Curr. 2014 May 27;6:ecurrents.eogt.aa5415d435fc886145bd7137a280a971. doi: 10.1371/currents.eogt.aa5415d435fc886145bd7137a280a971.
In contemporary oncology practices there is an increasing emphasis on concurrent evaluation of multiple genomic alterations within the biological pathways driving tumorigenesis. At the foundation of this paradigm shift are several commercially available tumor panels using next-generation sequencing to develop a more complete molecular blueprint of the tumor. Ideally, these would be used to identify clinically actionable variants that can be matched with available molecularly targeted therapy, regardless of the tumor site or histology. Currently, there is little information available on the post-analytic processes unique to next-generation sequencing platforms used by the companies offering these tests. Additionally, evidence of clinical validity showing an association between the genetic markers curated in these tests with treatment response to approved molecularly targeted therapies is lacking across all solid-tumor types. To date, there is no published data of improved outcomes when using the commercially available tests to guide treatment decisions. The uniqueness of these tests from other genomic applications used to guide clinical treatment decisions lie in the sequencing platforms used to generate large amounts of genomic data, which have their own related issues regarding analytic and clinical validity, necessary precursors to the evaluation of clinical utility. The generation and interpretation of these data will require new evidentiary standards for establishing not only clinical utility, but also analytical and clinical validity for this emerging paradigm in oncology practice.
在当代肿瘤学实践中，越来越强调在驱动肿瘤发生的生物学途径内对多种基因组改变进行同步评估。这种范式转变的基础是几种商业上可用的肿瘤检测板，它们使用下一代测序技术来绘制更完整的肿瘤分子蓝图。理想情况下，这些检测板将用于识别可与现有分子靶向疗法相匹配的具有临床可操作性的变异，而不考虑肿瘤部位或组织学类型。目前，对于提供这些检测的公司所使用的下一代测序平台特有的分析后流程，几乎没有相关信息。此外，在所有实体瘤类型中，均缺乏临床有效性证据，表明这些检测中筛选出的基因标记与对已批准的分子靶向疗法的治疗反应之间存在关联。迄今为止，尚无关于使用商业检测来指导治疗决策能改善预后的已发表数据。这些检测与用于指导临床治疗决策的其他基因组应用的不同之处在于，用于生成大量基因组数据的测序平台存在自身与分析和临床有效性相关的问题，而这些是评估临床效用的必要前提。这些数据的生成和解读将需要新的证据标准，不仅要确立临床效用，还要确立肿瘤学实践中这种新兴范式的分析和临床有效性。
