Tafe Laura J, Gorlov Ivan P, de Abreu Francine B, Lefferts Joel A, Liu Xiaoying, Pettus Jason R, Marotti Jonathan D, Bloch Kasia J, Memoli Vincent A, Suriawinata Arief A, Dragnev Konstantin H, Fadul Camilo E, Schwartz Gary N, Morgan Clinton R, Holderness Britt M, Peterson Jason D, Tsongalis Gregory J, Miller Todd W, Chamberlin Mary D
Departments of Pathology, Community and Family Medicine, Medicine, and Pharmacology & Toxicology, Comprehensive Breast Program, and Familial Cancer Program, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Departments of Pathology, Community and Family Medicine, Medicine, and Pharmacology & Toxicology, Comprehensive Breast Program, and Familial Cancer Program, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
Oncologist. 2015 Sep;20(9):1011-8. doi: 10.1634/theoncologist.2015-0097. Epub 2015 Jul 23.
Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients' tumor genetic profiles and provide treatment recommendations.
DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors.
During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months.
For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes.
Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment.
尽管肿瘤的基因分析是预测药物敏感性和耐药性的一个潜在有力工具,但其常规应用一直受到限制,因为临床医生往往不熟悉对这些信息的解读以及将其纳入临床实践。我们设立了一个分子肿瘤委员会(MTB)来解读个体患者的肿瘤基因图谱并提供治疗建议。
肿瘤标本的DNA在一个获得临床实验室改进修正案认证的实验室中进行测序,以识别一个包含50个基因的基因 panel(n = 34)或一个包含255个基因的基因 panel(n = 1)中的编码突变。病例由一个多学科的MTB进行评估,该委员会包括病理学家、肿瘤学家、血液学家、基础科学家和遗传咨询师。
在第一年,MTB评估了35个病例,其中32个病例被提交以获取关于靶向治疗的建议,3个病例被转诊以评估潜在的种系突变。在56.3%的病例中,MTB基于对肿瘤基因图谱和治疗史的评估,建议使用靶向药物进行治疗。随后,4名患者(12.5%)接受了MTB推荐的靶向治疗;4名患者中的3名仍在接受治疗,其中2名患者经历了持续超过10个月的临床获益。
对于大多数评估的病例,MTB能够基于可靶向的基因改变提供治疗建议。未采用MTB推荐治疗的最常见原因源于患者的偏好以及疾病极早期或极晚期的基因分析;很少遇到药物不可及的情况。临床医生和患者对分子分析和靶向治疗的认识提高,将改善对可能显著改善治疗结果的治疗的接受度和依从性。
由多学科分子肿瘤委员会(MTB)进行病例评估对于从个体化基因数据中获益并最大化临床影响至关重要。MTB的建议为大多数评估病例塑造了治疗选择。在少数接受MTB推荐治疗的患者中,疾病结果是积极的,并支持基于基因信息的治疗。