Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board.
Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board.
复制标题
DOI：
10.1200/po.16.00046
复制
发表时间：
2017
影响因子：
4.6
通讯作者：
Lauring J
中科院分区：
文献类型：
--
作者：
Dalton WB;Forde PM;Kang H;Connolly RM;Stearns V;Gocke CD;Eshleman JR;Axilbund J;Petry D;Geoghegan C;Wolff AC;Loeb DM;Pratilas CA;Meyer CF;Christenson ES;Slater SA;Ensminger J;Parsons HA;Park BH;Lauring J
用于个性化肿瘤治疗的肿瘤基因组分析正在临床实践中广泛应用，即使它正在临床试验中进行更正式的评估。鉴于基因组数据及其临床应用的复杂性，具有不同专业知识的分子肿瘤委员会可以为寻求在实践中实施个性化基因靶向治疗的肿瘤学家和患者提供指导。一个多学科分子肿瘤委员会审查了来自约翰霍普金斯西德尼金梅尔综合癌症中心连续转诊的肿瘤分子谱报告，为期3年。肿瘤委员会权衡了通过分子分析鉴定的基因组改变的可操作性证据，并提供了包括美国食品和药物管理局批准的药物治疗，匹配靶向治疗的临床试验，此类治疗的标签外使用以及额外的肿瘤或生殖细胞遗传检测的建议。155例患者接受了审查。在132例患者（85%）中发现了可操作的基因组改变。37例患者（24%）被推荐接受标签外治疗。11名患者接受了标签外治疗，13名患者参加了匹配靶向治疗的临床试验。接受匹配治疗的患者的中位无进展生存期为5个月（95% CI，2.9个月至未达到），6个月时的无进展生存概率为43%（95% CI，26%至71%）。缺乏当地可用的临床试验是肿瘤分析报告临床可行性的主要限制。分子肿瘤委员会建议对四分之一的患者进行标签外靶向治疗。结果是异质性的，虽然43%的患者接受基因组匹配治疗的临床获益持续至少6个月。在精确肿瘤学试验获得更多数据之前，分子肿瘤委员会可以帮助指导肿瘤分子检测的适当使用，以指导治疗。
Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months (95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43%(95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.