Abstract INTRODUCTION: Pediatric high-grade gliomas (pHGG) are among the most devastating childhood cancers. Due to their limited treatment options and tumor biology, brainstem (BS) pHGG are considered to have worse survival outcomes compared to non-brainstem (NBS) pHGG. METHODS: Detailed clinical data were gathered by trained registrars for all children diagnosed with a pHGG (including radiologically diagnosed brainstem tumors) in the Netherlands for the period 2003-2017. Tumors were grouped into BS and NBS tumors according to the ICD-O-3 topography codes. Differences in treatment characteristics were tested with the Chi-squared, Fisher exact or Mann-Whitney-Wilcoxon test. Median survival time was determined by Kaplan-Meier method. Trends and survival differences were tested with Cox Proportional-Hazards Models. RESULTS: In total, 276 pHGG patients (BS n=166, NBS n=110) were diagnosed during 2003-2017. Differences in first line treatment were found for neurosurgery (25% of BS versus 95% of NBS patients, p<0.001) and systemic therapy (20% of BS versus 70% of NBS, p<0.001). Notable, 10% of BS patients received temozolomide compared to 55% of NBS patients (p<0.001). No significant difference was found for first-line radiotherapy. However, total cumulative dose and number of fractions differed significantly (BS: median 44.8 Gy and 16 fractions; NBS: median 57.4 Gy and 30 fractions, both p<0.001), reflecting hypofractionation regimens in BS pHGG. Survival remained stable over time for both BS (p=0.9) and NBS (p=0.3). Median survival time was comparable between BS (9.7 months) and NBS patients (9.8 months, p=0.6).CONCLUSION: Despite differences in treatment characteristics we found comparable survival outcomes for BS and NBS pHGG. It remains unclear why survival for both BS and NBS pHGG in this retrospective population-based study is substantially inferior to published data. If the underlying reasons can be found in differences in treatment characteristics, data type (hospital-based versus ...