Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database

Abstract

Pediatric malignant gliomas represent a heterogeneous group of tumors. This publication reviews data from the first three HIT-GBM protocols. One important question is whether it makes sense to include both histologically confirmed high-grade glial tumors (HGG), and radiologically confirmed diffuse intrinsic pontine gliomas in a single study. Three-hundred-and ten patients (173 male, median age 10.0 years) were enrolled. Tumor locations were cerebral hemispheres: 80, basal ganglia: 38, pons: 134, non-pontine brain stem: 14, cerebellum: 14, spinal: 8, and overlapping areas: 22. Surgical resection was complete in 49, subtotal in 35, partial in 58, biopsy in 99, and no surgery in 69 cases. One-hundred-and twenty-three cases corresponded to WHO grade IV, 101 to III, and 15 to I/II. Two-hundred-and twenty-eight patients could be evaluated for response: CR: 8, PR: 32, SD: 116, and PD: 72. Median overall survival time was 1.03 years, and median event free survival was 0.54 years. Five year OS-rate was 10.28 +/- 2.1%. In the total database, tumor location, grading, and extent of surgical resection were prognostic factors, but the relevance differed in location subgroups with no relevance for sex, histological grading or extend of surgical resection in pontine tumors. Possible prognostic factors were not distributed homogeneously. Pontine tumors differed from cerebral hemisphere tumors concerning the frequency of previous diseases, the age at diagnosis (median age pons 7.9 years versus cerebral hemispheres 11.4 years), and the frequency of WHO grade III versus Grade IV (III:IV = 1.6 for pons, and 0.7 for cerebral hemispheres). We conclude that the biology of pontine glioma differs significantly from other HGG, and clinical studies should be separate with different endpoints.