Nguyen Thien, Mueller Sabine, Malbari Fatema
Department of Pediatrics, University of San Francisco, San Francisco, CA, United States.
Department of Neurology, Neurosurgery and Pediatrics, University of San Francisco, San Francisco, CA, United States.
Front Oncol. 2022 Apr 11;12:853034. doi: 10.3389/fonc.2022.853034. eCollection 2022.
Surgery, chemotherapy and radiation have been the mainstay of pediatric brain tumor treatment over the past decades. Recently, new treatment modalities have emerged for the management of pediatric brain tumors. These therapies range from novel radiotherapy techniques and targeted immunotherapies to checkpoint inhibitors and T cell transfer therapies. These treatments are currently investigated with the goal of improving survival and decreasing morbidity. However, compared to traditional therapies, these novel modalities are not as well elucidated and similarly has the potential to cause significant short and long-term sequelae, impacting quality of life. Treatment complications are commonly mediated through direct drug toxicity or vascular, infectious, or autoimmune mechanisms, ranging from immune effector cell associated neurotoxicity syndrome with CART-cells to neuropathy with checkpoint inhibitors. Addressing treatment-induced complications is the focus of new trials, specifically improving neurocognitive outcomes. The aim of this review is to explore the pathophysiology underlying treatment related neurologic side effects, highlight associated complications, and describe the future direction of brain tumor protocols. Increasing awareness of these neurologic complications from novel therapies underscores the need for quality-of-life metrics and considerations in clinical trials to decrease associated treatment-induced morbidity.
在过去几十年里,手术、化疗和放疗一直是小儿脑肿瘤治疗的主要手段。最近,出现了用于治疗小儿脑肿瘤的新治疗模式。这些疗法包括新型放疗技术、靶向免疫疗法、检查点抑制剂和T细胞转移疗法。目前对这些治疗方法进行研究的目的是提高生存率并降低发病率。然而,与传统疗法相比,这些新模式尚未得到充分阐明,同样有可能导致严重的短期和长期后遗症,影响生活质量。治疗并发症通常通过直接药物毒性或血管、感染或自身免疫机制介导,范围从与嵌合抗原受体T细胞(CART细胞)相关的免疫效应细胞相关神经毒性综合征到与检查点抑制剂相关的神经病变。解决治疗引起的并发症是新试验的重点,特别是改善神经认知结果。本综述的目的是探讨治疗相关神经副作用的病理生理学,突出相关并发症,并描述脑肿瘤治疗方案的未来方向。对这些新疗法引起的神经并发症的认识不断提高,凸显了在临床试验中需要生活质量指标和考量因素,以降低相关治疗引起的发病率。