Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, M/S MB.8.501, PO Box 5371, Seattle, WA, 98105, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
J Neurooncol. 2020 Jul;148(3):607-617. doi: 10.1007/s11060-020-03558-w. Epub 2020 Jun 16.
Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation.
We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated.
Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG.
Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.
除了局部放疗外，对于儿童高级别胶质瘤（pHGG）目前尚无共识的标准治疗方法，且患儿预后仍然较差。我们描述了西雅图儿童医院采用替莫唑胺、伊立替康和贝伐珠单抗（TIB）三联维持治疗方案治疗的最大分子特征患儿队列，这些患儿在放疗后接受了治疗。
我们回顾性分析了 2009 年至 2018 年在西雅图儿童医院接受 TIB 治疗的 36 名患儿的资料，并采用 Kaplan-Meier 方法分析生存情况。通过靶向 DNA 测序进行分子分析，并评估了毒性、类固醇使用和姑息治疗的应用。
中位诊断年龄为 10.9 岁（18 个月-18 岁）。共检测到 26 个基因的遗传改变，并与已识别的分子亚组相吻合，包括 H3 K27M 突变（12 例）、H3F3A G34 突变（2 例）、IDH 突变（4 例）和高度突变谱（4 例）。15 例患者（42%）完成了 12 个周期的维持治疗。与化疗延迟或修改相关的副作用包括血小板减少症（28%）和恶心/呕吐（19%），其中替莫唑胺剂量最常被修改。中位无进展生存期（EFS）和总生存期（OS）分别为 16.2 个月和 20.1 个月，DIPG 患儿的生存期更短，分别为 9.3 个月和 13.3 个月。DIPG 患儿 1、2 和 5 年的生存率分别为 80%、10%和 0%，其他 pHGG 患儿的生存率分别为 85%、38%和 16%。
我们的单中心经验表明，该三联治疗方案具有良好的耐受性，与历史上的单药替莫唑胺相比，DIPG 患儿的生存期延长。pHGG 的生存情况与类似的三联治疗方案相当，优于历史药物，但治愈很少见。pHGG 患儿仍然是标准治疗联合新型治疗方法研究的优秀候选者。
