Venur Vyshak Alva, Karivedu Vidhya, Ahluwalia Manmeet S
Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
Division of Hematology and Oncology, University of Cincinnati, Cincinnati, OH, United States.
Handb Clin Neurol. 2018;149:137-153. doi: 10.1016/B978-0-12-811161-1.00011-6.
Central nervous system metastases cause grave morbidity in patients with advanced malignancies. Lung cancer, breast cancer, and melanoma are the three most common causes of brain metastases. Although the exact incidence of brain metastases is unclear, there appears to be an increasing incidence which has been attributed to longer survival, better control of systemic disease, and better imaging modalities. Until recently surgical resection of solitary or symptomatic brain metastases, and radiation therapy (either whole-brain radiation therapy or stereotactic radiation) were the mainstay of treatment for patients with brain metastases. The majority of traditional chemotherapies have shown limited activity in the central nervous system, which has been attributed to the blood-brain barrier and the molecular structure of the used agents. The discovery of driver mutations and drugs targeting these mutations has changed the treatment landscape. Several of these targeted small-molecule tyrosine kinase inhibitors do cross the blood-brain barrier and/or have shown activity in the central nervous system. Another major advance in the care of brain metastases has been the advent of new immunotherapeutic agents, for which initial studies have shown intracranial activity. In this chapter, we will review the unique challenges in the treatment of brain metastases. The pertinent clinical studies of chemotherapy in brain metastases will be discussed. The currently reported clinical trials and evidence for use of targeted therapies and immunotherapeutic agents will be emphasized.
中枢神经系统转移瘤会给晚期恶性肿瘤患者带来严重的发病情况。肺癌、乳腺癌和黑色素瘤是脑转移瘤最常见的三大病因。尽管脑转移瘤的确切发病率尚不清楚，但发病率似乎呈上升趋势，这归因于患者生存期延长、全身疾病得到更好控制以及成像方式的改进。直到最近，手术切除孤立性或有症状的脑转移瘤以及放射治疗（全脑放射治疗或立体定向放射治疗）一直是脑转移瘤患者的主要治疗手段。大多数传统化疗药物在中枢神经系统中的活性有限，这归因于血脑屏障和所用药物的分子结构。驱动基因突变以及针对这些突变的药物的发现改变了治疗格局。其中几种靶向小分子酪氨酸激酶抑制剂确实能够穿过血脑屏障和/或已在中枢神经系统中显示出活性。脑转移瘤治疗的另一项重大进展是新型免疫治疗药物的出现，初步研究表明这些药物在颅内具有活性。在本章中，我们将回顾脑转移瘤治疗中面临的独特挑战。将讨论脑转移瘤化疗的相关临床研究。将重点介绍目前报道的关于使用靶向治疗和免疫治疗药物的临床试验及证据。
