Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Neuro-Oncology, Department of Neurology, Stephen E. Catherine Pappas Center for Neuro Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Neurosurgery. 2020 Sep 1;87(3):E281-E288. doi: 10.1093/neuros/nyaa095.
Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brain metastases from melanoma and nonsmall cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones. In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities. We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.
免疫检查点抑制剂通过干扰细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）和程序性死亡 1（PD1）途径来增强免疫对肿瘤的识别。在过去的十年中，这些药物显著改善了转移性癌症患者的预后前景。最近来自回顾性分析和少数前瞻性研究的数据表明，检查点抑制剂作为单一药物或与放射治疗联合使用，对黑色素瘤和非小细胞肺癌的脑转移具有活性。一些研究报告了与全身治疗相当的颅内反应率。在这篇综述中，我们提供了支持抗 CTLA4 和抗 PD1 药物在脑转移瘤中应用的临床数据的综合总结。我们还涉及了评估患者颅内反应和免疫治疗特异性毒性的具体考虑因素。我们得出结论，一部分脑转移患者从将检查点抑制剂加入标准治疗方法（包括放疗和手术）中获益。
