High grade gliomas in young children: The South Thames Neuro-Oncology unit experience and recent advances in molecular biology and targeted therapies

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.

高级别胶质瘤（high grade gliomas, HGG）预后极差，患者生存率仅为15%~35%。约10%~12%的儿童高级别胶质瘤发生于幼儿群体，其分子生物学特征与临床结局均与年长患儿存在显著差异。本研究纳入2011年至2018年间新诊断为非脑干型高级别胶质瘤的4名年龄不足5岁的患儿，均接受了手术联合BBSFOP化疗方案治疗。其中2名患儿因肿瘤进展死亡，剩余2名患儿在确诊后3.8年和3.9年时仍未接受放疗且存活：其中1名患儿停药后未检测到肿瘤复发；另1名患儿的肿瘤携带KCTD16:NTRK2融合基因，后续接受了拉罗替尼（larotrectinib）治疗。此外，本研究还综述了幼儿高级别胶质瘤的常规诊疗策略、临床结局，以及分子生物学与靶向治疗领域的最新进展。婴儿胶质瘤可根据携带临床可靶向致癌驱动基因的特征分为不同分子亚型。基于化疗的诊疗策略可帮助幼儿高级别胶质瘤患儿避免或推迟放疗的使用需求。挖掘NTRK、ALK、ROS1及MET抑制剂的治疗潜力，有望优化治疗手段组合，从而改善这类患儿的现有临床结局。