PGY3 Internal Medicine Resident, Department of Internal Medicine, Cleveland Clinic Akron General, 1, Akron General Ave, Akron, OH, 44307, USA.
PGY1 Internal Medicine Resident, Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, NA10, Cleveland, OH, 44195, USA.
Curr Treat Options Oncol. 2019 Feb 15;20(3):19. doi: 10.1007/s11864-019-0618-5.
In the past, the standard of care for treatment of BM was whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. There has been a greater role for medical therapies in the last two decades due to the discovery of driver mutations and corresponding targeted therapies. These innovations have dramatically altered the approach to treating these patients. Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma. Disease-specific graded prognostic assessments have identified prognostic factors for each of the major tumor types associated with BM. These reflect the increased treatment sensitivity of these tumors to specific agents. Furthermore, there is a difference in the genetic makeup of BM compared to their primary tumor. Genomic studies of BM patients comparing somatic point mutations and copy number variations with their primary tumor have demonstrated that while both the primary tumor and BM share a number of common mutations, BM can often develop distinct mutations. Therefore, there is a need to individualize systemic therapies in BM. Several organizations including the Food and Drug Administration and the American Society of Clinical Oncology now emphasize the inclusion of BM patients in various phases of clinical drug development.
在过去,治疗 BM 的标准治疗方法是全脑放射治疗(WBRT)、立体定向放射外科(SRS)和手术。由于发现了驱动突变和相应的靶向治疗,在过去二十年中,医学治疗在其中发挥了更大的作用。这些创新极大地改变了治疗这些患者的方法。一些重要的突变包括小细胞肺癌中的表皮生长因子受体(EGFR)和间变性淋巴瘤激酶(ALK)突变、乳腺癌中的人表皮生长因子受体(HER2)突变和黑色素瘤中的 BRAF 突变。针对特定疾病的分级预后评估确定了与 BM 相关的主要肿瘤类型的预后因素。这些反映了这些肿瘤对特定药物的治疗敏感性增加。此外,BM 与原发性肿瘤相比,其遗传构成存在差异。对 BM 患者的基因组研究比较了体细胞点突变和拷贝数变异与原发性肿瘤,结果表明,尽管原发性肿瘤和 BM 共享许多共同突变,但 BM 通常可以发展出独特的突变。因此,需要对 BM 中的系统治疗进行个体化。包括美国食品和药物管理局和美国临床肿瘤学会在内的几个组织现在强调将 BM 患者纳入各种临床药物开发阶段。