Abstract

High grade gliomas (HGG) have a dismal prognosis with survival rates of 15–35%. Approximately 10–12% of pediatric HGG occur in young children and their molecular biology and clinical outcomes differ from those arising at older ages. We report on four children aged <5 years newly diagnosed with non-brainstem HGG between 2011 and 2018 who were treated with surgery and BBSFOP chemotherapy. Two died of tumor progression. The other two are still alive without radiotherapy at 3.8 and 3.9 years from diagnosis: one of whom remains disease-free off treatment; and the other one, whose tumor harbored a KCTD16:NTRK2 fusion, went on to receive larotrectinib. Additionally we review the general management, outcomes and latest updates in molecular biology and targeted therapies for young children with HGG. Infant gliomas can be stratified in molecular subgroups with clinically actionable oncogenic drivers. Chemotherapy-based strategies can avoid or delay the need for radiotherapy in young children with HGG. Harnessing the potential of NTRK, ALK, ROS1 and MET inhibitors offers the opportunity to optimize the therapeutic armamentarium to improve current outcomes for these children.

 抽象的

高级别胶质瘤 (HGG) 的预后很差，生存率为 15-35%。大约 10-12% 的儿科 HGG 发生在幼儿中，其分子生物学和临床结果与老年人不同。我们报告了 2011 年至 2018 年间新诊断出患有非脑干 HGG 的 4 名 <5 岁儿童，他们接受了手术和 BBSFOP 化疗。其中两人死于肿瘤进展。另外两人在诊断后 3.8 和 3.9 年时在未接受放射治疗的情况下仍然存活：其中一人在接受治疗后仍保持无病状态；另一名患者的肿瘤含有 KCTD16:NTRK2 融合体，继续接受 larotrectinib 治疗。此外，我们还回顾了 HGG 幼儿的一般管理、结果和分子生物学和靶向治疗的最新进展。婴儿神经胶质瘤可以根据临床上可操作的致癌驱动因素分为分子亚组。基于化疗的策略可以避免或延迟患有 HGG 的幼儿对放射治疗的需要。利用 NTRK、ALK、ROS1 和 MET 抑制剂的潜力提供了优化治疗设备的机会，以改善这些儿童目前的结果。