Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial

Background: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/Temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathological and molecular data. Methods: Radiological, pathological and molecular data were correlated with trial clinical information to retrospectively re-evaluate event free and overall survival. Results: One-hundred thirteen patients were randomized to the RT/TMZ arm (n =54) or the RT/TMZ+BEV (BEV arm; n =59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathological diagnosis was available in all cases and molecular data in 86/113. H3 K27M histone mutations were present in 23/32 Midline cases and H3 G34R/V mutations in 7/54 Cerebral cases. Total/near-total resection occurred in 44/68 (65%) Cerebral cases but only 5/45 (11%) Midline cases (p <0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than Cerebral tumors (10/68, p <0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (p <0.05). Pseudoprogression occurred in 8/111 (6.2%) cases. Conclusions: This study has shown that the poor outcome of midline tumors (compared to cerebral) may be related to 1) lesser surgical resection, 2) H3 K27M histone mutations, and 3) higher leptomeningeal dissemination.