Department of Medicine, Division of Solid Tumor Oncology.
Clinical Research Administration.
Ann Oncol. 2017 Sep 1;28(9):2298-2304. doi: 10.1093/annonc/mdx294.
Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making.
All physicians who consented patients to MSK-IMPACT, a next-generation hybridization capture assay, in tumor types where molecular profiling is not routinely performed were asked to complete a questionnaire for each patient. Physician determination of genomic 'actionability' was compared to an expertly curated knowledgebase of somatic variants. Reported management decisions were compared to chart review.
Responses were received from 146 physicians pertaining to 1932 patients diagnosed with 1 of 49 cancer types. Physicians indicated that sequencing altered management in 21% (331/1593) of patients in need of a treatment change. Among those in whom treatment was not altered, physicians indicated the presence of an actionable alteration in 55% (805/1474), however, only 45% (362/805) of these cases had a genomic variant annotated as actionable by expert curators. Further evaluation of these patients revealed that 66% (291/443) had a variant in a gene associated with biologic but not clinical evidence of actionability or a variant of unknown significance in a gene with at least one known actionable alteration. Of the cases annotated as actionable by experts, physicians identified an actionable alteration in 81% (362/445). In total, 13% (245/1932) of patients were enrolled to a genomically matched trial.
Although physician and expert assessment differed, clinicians demonstrate substantial awareness of the genes associated with potential actionability and report using this knowledge to inform management in one in five patients.
NCT01775072.
基因组分析越来越多地被纳入肿瘤学研究和癌症患者的临床治疗中。我们旨在确定本中心的医生对企业级临床测序的看法和使用情况，包括检测是否改变了治疗方案，以及做出这一决策的原因。
所有同意患者进行 MSK-IMPACT 下一代杂交捕获检测的医生（在这些患者中，分子谱分析未常规进行），都需要为每位患者填写一份调查问卷。医生对基因组“可操作性”的判断与经过精心整理的体细胞变异知识库进行了比较。报告的治疗决策与病历复查进行了比较。
共有 146 名医生对 1932 名诊断为 49 种癌症类型之一的患者做出了回应。医生表示，测序改变了 21%（331/1593）需要改变治疗方案的患者的治疗方案。在未改变治疗方案的患者中，医生表示存在可操作的改变的占 55%（805/1474），然而，在这些病例中，只有 45%（362/805）的病例中有专家注释为可操作的基因组变异。对这些患者的进一步评估显示，66%（291/443）的患者在基因中存在与生物学相关但没有临床可操作性证据的变异，或在至少有一个已知可操作变异的基因中存在未知意义的变异。在专家注释为可操作的病例中，医生识别出可操作的改变占 81%（362/445）。总的来说，13%（245/1932）的患者被纳入了基因匹配的试验。
尽管医生和专家的评估存在差异，但临床医生对与潜在可操作性相关的基因有了充分的认识，并报告说在五分之一的患者中使用这些知识来指导治疗方案。
NCT01775072。
