Midwestern University Arizona College of Osteopathic Medicine, Glendale, Arizona, USA.
Aga Khan University, Karachi, Pakistan.
World Neurosurg. 2021 Jul;151:e839-e856. doi: 10.1016/j.wneu.2021.04.134. Epub 2021 May 8.
Radiation therapy (RT) is the cornerstone of management of malignant brain tumors, but its efficacy is limited in hypoxic tumors. Although numerous radiosensitizer compounds have been developed to enhance the effect of RT, progress has been stagnant. Through this systematic review, we provide an overview of radiosensitizers developed for malignant brain tumors, summarize their safety and efficacy, and evaluate areas for possible improvement.
Following PRISMA guidelines, PubMed, EMBASE, Cochrane, and Web of Science were searched using terminology pertaining to radiosensitizers for brain tumor RT. Articles reporting clinical evidence of nonantineoplastic radiosensitizers with RT for malignant central nervous system tumors were included. Data of interest were presumed mechanism of action, median overall survival (OS), progression-free survival (PFS), and adverse events.
Twenty-two unique radiosensitizers were identified. Only 2/22 agents (fluosol with oxygen, and efaproxiral) showed improvement in OS in patients with glioblastoma and brain metastasis, respectively. A larger study was not able to confirm the latter. Improved PFS was reported with use of metronidazole, sodium glycididazole, and chloroquine. There was a wide range of toxicities, which prompted change of schedule or complete discontinuation of 9 agents.
Progress in radiosensitizers for malignant CNS tumors has been limited. Only 2 radiosensitizers have shown limited improvement in survival. Alternative strategies such as synthetic drug design, based on a mechanism of action that is independent of crossing the blood-brain barrier, may be necessary. Use of drug development strategies using new technologies to overcome past challenges is necessary.
放射治疗（RT）是恶性脑肿瘤治疗的基石，但在缺氧肿瘤中的疗效有限。尽管已经开发了许多放射增敏剂化合物来增强 RT 的效果，但进展一直停滞不前。通过这项系统评价，我们提供了恶性脑肿瘤开发的放射增敏剂概述，总结了它们的安全性和疗效，并评估了可能改进的领域。
根据 PRISMA 指南，使用与脑肿瘤 RT 的放射增敏剂相关的术语，在 PubMed、EMBASE、Cochrane 和 Web of Science 上进行了搜索。纳入报告非抗肿瘤放射增敏剂与恶性中枢神经系统肿瘤 RT 相关的临床证据的文章。感兴趣的数据包括作用机制、中位总生存期（OS）、无进展生存期（PFS）和不良事件。
确定了 22 种独特的放射增敏剂。只有 2/22 种药物（氟碳氧与氧气，以及 efaproxiral）在胶质母细胞瘤和脑转移患者中显示 OS 改善。一项更大的研究未能证实后者。使用甲硝唑、甘氨双唑钠和氯喹可改善 PFS。毒性范围广泛，导致 9 种药物改变方案或完全停用。
恶性中枢神经系统肿瘤的放射增敏剂进展有限。只有 2 种放射增敏剂在生存方面显示出有限的改善。可能需要替代策略，例如基于独立于血脑屏障穿越机制的作用机制的合成药物设计。有必要使用新技术的药物开发策略来克服过去的挑战。
