Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.
Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.
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DOI：
10.1002/pbc.26002
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发表时间：
2016-08
影响因子：
3.2
通讯作者：
Kentsis A
中科院分区：
文献类型：
--
作者：
Ortiz MV;Kobos R;Walsh M;Slotkin EK;Roberts S;Berger MF;Hameed M;Solit D;Ladanyi M;Shukla N;Kentsis A
儿科肿瘤学家已经开始利用肿瘤基因图谱来匹配患者的靶向治疗。在纪念斯隆凯特琳癌症中心（MSKCC），我们开发了儿科分子肿瘤委员会（PMTB），以跟踪，整合和解释临床基因组分析和潜在的靶向治疗建议。该回顾性病例系列包括2014年7月至2015年6月由MSKCC PMTB审查的所有患者。病例由治疗肿瘤学家提交，潜在的治疗建议基于牛津循证医学中心的修订指南。在研究期间，39例患者共进行了41次介绍。神经胶质瘤、急性髓性白血病和神经母细胞瘤是最常审查的病例。45个分子测序谱中的39个（87%）利用杂交捕获靶向基因组测序。在41份报告中的30份（73%）中，PMTB提供了治疗建议，其中19份（46%）得到实施。其中21项（70%）建议涉及靶向治疗。3项（14%）靶向治疗建议已发表证据支持建议（证据等级1-2），8项（36%）建议有临床前证据（3级），11项（50%）建议基于假设的生物学依据（4级）。MSKCC PMTB能够对基因组分析进行临床相关的解释。临床基因组学的有效使用预计需要新的和改进的工具，以归因于致病的意义和治疗actionability。在干预性前瞻性临床试验中，将需要制定具体的规则驱动的临床方案，以纳入和评估基因组和分子谱。
Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1–2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials.