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癌症免疫疗法和靶向治疗的神经后遗症。

Neurological sequelae of cancer immunotherapies and targeted therapies.

机构信息

Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Units, Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Units, Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

Lancet Oncol. 2016 Dec;17(12):e529-e541. doi: 10.1016/S1470-2045(16)30571-X.

Abstract

Neurological complications of cancer and of anticancer treatments can be substantially disabling to patients, especially with classic chemotherapies. As a rare but important complication, targeted therapies might also result in similar unwanted effects, partly because inhibition of VEGF is a common downstream effect. Therapeutic antibodies, such as the CD20-depleting antibody rituximab, and underlying haematological malignancies, can induce long-lasting cellular immunosuppression, predisposing patients to opportunistic CNS infections, such as progressive multifocal leukoencephalopathy, where treatment-induced recovery can result in severe reconstitution of immune inflammatory syndromes of the central nervous system. Immune-related neurological adverse events, particularly from immune-activating checkpoint inhibitors, occur as a result of immune activation, resulting in organ-specific autoimmune-like disease. The prevalence of immune-related neurological adverse events might only be about 1%-a low prevalence compared with toxicities in other organs-but it constitutes new patterns of neurological toxic forms, which could result in considerable morbidity and fatal outcomes. Clinicians should be aware of treatment-associated neurotoxicity, and consider discontinuation of the drug with parallel supportive measures to help patients.

摘要

癌症和抗癌治疗的神经并发症会严重影响患者的身体机能,特别是在使用经典化疗药物的情况下。作为一种罕见但重要的并发症,靶向治疗也可能导致类似的不良反应,部分原因是抑制 VEGF 是一种常见的下游效应。治疗性抗体,如 CD20 耗竭性抗体利妥昔单抗,以及潜在的血液系统恶性肿瘤,可能会导致长期的细胞免疫抑制,使患者易患中枢神经系统机会性感染,如进行性多灶性白质脑病,其中治疗诱导的恢复可能导致中枢神经系统免疫炎症综合征的严重重建。免疫相关的神经不良反应,特别是来自免疫激活检查点抑制剂的不良反应,是由于免疫激活引起的,导致特定器官的自身免疫样疾病。免疫相关的神经不良反应的发生率可能只有 1%左右——与其他器官的毒性相比,这一比例较低——但它构成了新的神经毒性形式,可能导致相当大的发病率和死亡率。临床医生应该意识到与治疗相关的神经毒性,并考虑停用药物,同时采取支持性措施帮助患者。

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