f Institutional implementation of clinical tumor profiling on an unselected cancer population
f Institutional implementation of clinical tumor profiling on an unselected cancer population
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DOI：
10.1172/jci.insight.87062
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发表时间：
2016-11-17
期刊：
影响因子：
8
通讯作者：
MacConaill, Laura E.
中科院分区：
文献类型：
--
作者：
Sholl, Lynette M.;Do, Khanh;MacConaill, Laura E.
背景患者癌症的全面基因组分析可用于诊断、监测和推荐治疗。在企业范围内的肿瘤分析的临床实施，乳腺癌患者人群尚未得到证实。我们在我们的联合癌症中心为所有成人和儿童患者部署了混合捕获和大规模平行测序检测（OncoPanel）。结果由病理学家根据可操作性进行分类。我们报告了前3,727例患者的测试结果。我们的队列由不受疾病部位或阶段限制的癌症患者组成。在所有同意的患者中，一半有足够的和可用的（>20%的肿瘤）材料进行分析;一旦在实验室收到标本进行病理学审查，73%的人被评为足以进行基因组检测。当获得足够的DNA时，OncoPanel在96%的病例中产生结果。73%的患者存在可采取行动或提供信息的改变;其中仅19%代表了治疗分层的当前标准治疗。这些发现概括了以前对常见癌症的研究，但也确定了与靶向治疗反应相关的改变，包括AXL和EGFR。在罕见的癌症中，潜在的可操作的改变表明在基因组分析中“癌症不可知”方法的效用。回顾性分析揭示了可能为治疗反应提供信息的背景基因组特征，以及通过基因组分析修订诊断显著改变临床管理的实例。广泛的基于测序的测试部署在一个癌症队列是可行的。基因组结果可能会改变不同情况下的管理;然而，必须克服额外的障碍，才能实现大规模的精准癌症医学。
BACKGROUND. Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported.METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested.RESULTS. Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including in AXL and EGFR, associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a "cancer-agnostic" approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where diagnoses revised by genomic profiling markedly changed clinical management.CONCLUSIONS. Broad sequencing-based testing deployed across an unselected cancer cohort is feasible. Genomic results may alter management in diverse scenarios; however, additional barriers must be overcome to enable precision cancer medicine on a large scale.