Pollack Ian F, Agnihotri Sameer, Broniscer Alberto
J Neurosurg Pediatr. 2019 Mar 1;23(3):261-273. doi: 10.3171/2018.10.PEDS18377.
Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. While tumors such as medulloblastomas have been historically grouped into standard- and high-risk categories, it is now recognized that these tumors encompass four or more molecular subsets with distinct clinical and molecular characteristics. Likewise, high-grade glioma, which for decades was considered a single high-risk entity, is now known to comprise multiple subsets of tumors that differ in terms of patient age, tumor location, and prognosis. The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. Accordingly, the present era is one in which treatment is evolving from the historical standard of radiation and conventional chemotherapy to a more nuanced approach in which these modalities are applied in a risk-adapted framework and molecularly targeted therapies are implemented to augment or, in some cases, replace conventional therapy. Herein, the authors review advances in the categorization and treatment of several of the more common pediatric brain tumors and discuss current and future directions in tumor management that hold significant promise for patients with these challenging tumors.
脑肿瘤是儿童最常见的实体瘤，不幸的是，许多亚型的长期预后仍然不尽人意。然而，在过去几年中，由于高分辨率基因组学、表观遗传学和转录组学分析，我们对这些肿瘤分子基础的理解取得了显著进展，这为改善肿瘤分类和分子靶向治疗提供了思路。虽然髓母细胞瘤等肿瘤在历史上被分为标准风险和高风险类别，但现在人们认识到这些肿瘤包含四个或更多具有不同临床和分子特征的分子亚群。同样，几十年来被认为是单一高风险实体的高级别胶质瘤，现在已知由多个肿瘤亚群组成，这些亚群在患者年龄、肿瘤位置和预后方面存在差异。室管膜瘤的情况更为复杂，至少已描述了九个肿瘤亚群。相反，大多数毛细胞型星形细胞瘤似乎是由改变单一可治疗靶向分子途径的基因变化引起的。因此，当前时代正从放疗和传统化疗的历史标准治疗向一种更细致入微的方法发展，即在风险适应框架中应用这些治疗方式，并实施分子靶向治疗以增强或在某些情况下取代传统治疗。在此，作者回顾了几种较常见儿童脑肿瘤分类和治疗方面的进展，并讨论了肿瘤管理的当前和未来方向，这些方向对患有这些具有挑战性肿瘤的患者具有重大前景。
