Abstract
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 pathologic and molecular data. Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS). 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). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 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 in 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 of 111 (6.2%) cases. This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination.
Highlights
The HERBY trial was a phase II, open-label, randomized, multicenter study comparing the benefit of adding the antiangiogenic agent Bevacizumab (BEV arm) to conventional radiotherapy (RT) and Temozolomide (TMZ; radiotherapy/ temozolomide (RT/TMZ) arm) in children between 3 and 18 years of age presenting with newly diagnosed, non-brainstem high-grade gliomas (HGG)
This study has shown that the poor outcome of midline tumors may be related to [1] lesser surgical resection, [2] H3 K27M histone mutations, and [3] higher leptomeningeal dissemination
Note: Supplementary data for this article are available at Clinical Cancer Research Online
Summary
The HERBY trial was a phase II, open-label, randomized, multicenter study comparing the benefit of adding the antiangiogenic agent Bevacizumab (BEV arm) to conventional radiotherapy (RT) and Temozolomide (TMZ; RT/TMZ arm) in children between 3 and 18 years of age presenting with newly diagnosed, non-brainstem high-grade gliomas (HGG). The primary measures of response were overall survival (OS) and event-free survival (EFS) after 12 months; the study outcomes were recently published, demonstrating no overall advantage conferred by the addition of Bevacizumab [1]. HGGs are one of the most common malignant primary neoplasms of the pediatric central nervous system, occurring with a frequency of approximately 0.85 per 100,000 [2] These tumors were thought to be similar to HGG occurring in adults; molecular, genetic, and biological data show that they are phenotypically distinct neoplasms [3]. Greater understanding of their biology offers the potential for a more tailored approach to treatment, employing novel therapeutic techniques targeting molecular and genetic pathways
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