Yale Cancer Center.
Yale Brain Tumor Center.
Curr Opin Neurol. 2019 Dec;32(6):907-916. doi: 10.1097/WCO.0000000000000756.
Median survival after the diagnosis of brain metastases has historically been on the order of months. With the recent development of immune checkpoint inhibitors, intracranial activity and durable responses have been observed in brain metastases on multiple phase 2 clinical trials, which have primarily been conducted in patients with melanoma. Immune-related adverse events related to checkpoint inhibitor therapy of brain metastasis can present unique challenges for the clinician and underscore the need for a multidisciplinary team in the care of these patients. The goal of this review is to address the current knowledge, limitations of understanding, and future directions in research regarding immune therapy trials and neurologic toxicities based on retrospective, prospective, and case studies.
Immune therapy has the potential to exacerbate symptomatic edema and increase the risk of radiation necrosis in previously irradiated lesions. Neurologic toxicities will likely increase in prevalence as more patients with brain metastatic disease are eligible for immune therapy.
An improved understanding and heightened awareness of the unique neurologic toxicities that impact this patient group is vital for mitigating treatment-related morbidity and mortality.
脑转移瘤诊断后的中位生存时间历来为数月。随着免疫检查点抑制剂的近期发展，在多个 2 期临床试验中观察到脑转移瘤的颅内活性和持久反应，这些试验主要在黑色素瘤患者中进行。与脑转移瘤的检查点抑制剂治疗相关的免疫相关不良事件可能会给临床医生带来独特的挑战，并强调需要多学科团队来治疗这些患者。本综述的目的是根据回顾性、前瞻性和病例研究，针对免疫治疗试验和神经毒性方面的现有知识、理解的局限性和未来研究方向进行探讨。
免疫治疗有可能使症状性水肿恶化，并增加既往照射病灶发生放射性坏死的风险。随着更多符合免疫治疗条件的脑转移瘤患者的出现，神经毒性的发生率可能会增加。
为了减轻治疗相关发病率和死亡率，对于影响这一患者群体的独特神经毒性的更好理解和更高认识至关重要。
