Tosi Umberto, Souweidane Mark
Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Department of Neurological Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pharmaceutics. 2020 Jul 14;12(7):660. doi: 10.3390/pharmaceutics12070660.
Diffuse intrinsic pontine gliomas (DIPGs) are a pontine subtype of diffuse midline gliomas (DMGs), primary central nervous system (CNS) tumors of childhood that carry a terrible prognosis. Because of the highly infiltrative growth pattern and the anatomical position, cytoreductive surgery is not an option. An initial response to radiation therapy is invariably followed by recurrence; mortality occurs approximately 11 months after diagnosis. The development of novel therapeutics with great preclinical promise has been hindered by the tightly regulated blood-brain barrier (BBB), which segregates the tumor comportment from the systemic circulation. One possible solution to this obstacle is the use of convection enhanced delivery (CED), a local delivery strategy that bypasses the BBB by direct infusion into the tumor through a small caliber cannula. We have recently shown CED to be safe in children with DIPG (NCT01502917). In this review, we discuss our experience with CED, its advantages, and technical advancements that are occurring in the field. We also highlight hurdles that will likely need to be overcome in demonstrating clinical benefit with this therapeutic strategy.
弥漫性脑桥内在型胶质瘤（DIPG）是弥漫性中线胶质瘤（DMG）的一种脑桥亚型，是儿童原发性中枢神经系统（CNS）肿瘤，预后极差。由于其高度浸润性生长模式和解剖位置，减瘤手术不是一种选择。放疗后的初始反应总是会接着复发；诊断后约11个月会出现死亡。具有很大临床前前景的新型疗法的开发受到严格调控的血脑屏障（BBB）的阻碍，血脑屏障将肿瘤与体循环分隔开来。解决这一障碍的一种可能方法是使用对流增强递送（CED），这是一种局部递送策略，通过小口径套管直接注入肿瘤来绕过血脑屏障。我们最近已证明CED在患有DIPG的儿童中是安全的（NCT01502917）。在本综述中，我们讨论了我们在CED方面的经验、其优势以及该领域正在出现的技术进步。我们还强调了在证明这种治疗策略的临床益处方面可能需要克服的障碍。
