Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

Table 1

Summary of the main clinical trials in pediatric HGG.

Agent and mechanism of action	Treatment	Study design	Status at diagnosis	Outcome	Reference
Alkylating agent (TMZ)	RT + TMZ	Phase II	Newly diagnosed HGG	EFS3y: 11 ± 3%; OS3y: 22 ± 5%	[4]
	TMZ	Phase II	Relapsed or progressive HGG	mOS 4.7 months; response rate: 12%	[5]
	RT + TMZ	Phase II	Newly diagnosed HGG	PFS1y: 43% ± 9%; PFS2y: 11% ± 5%; OS1y: 63% ± 8%; OS2y: 21% ± 7%	[6]
	TMZ	Phase II	Relapsed or progressive HGG	mPFS: 3 months; PFS6m: 33%; mOS: 4 months; OS6m: 37.5%	[7]
Receptor tyrosine kinase inhibitors
EGFR inhibitor (erlotinib)	RT + erlotinib	Phase I	Newly diagnosed HGG	PFS1y: 56% ± 10%; PFS2y: 35% ± 12%; OS1y:78% ± 9%; OS2y: 48% ± 12%	[31]
PDGFR inhibitor (imatinib)	Erlotinib	Phase I	Relapsed or progressive HGG	mPFS: 1.5 months; mOS: 4.1 months; SD: 28%	[33]
	Imatinib	Phase I	Relapsed or progressive HGG	EFS6m: 17.9% ± 6.6%; EFS12m: 0%	[51]
Antiangiogenic agent (BVZ)	BVZ + irinotecan	Phase II	Relapsed or progressive HGG	mPFS: 2.25 months; mOS: 6.25 months; SD: 33.3%	[65]
	BVZ + irinotecan	Phase II	Relapsed or progressive HGG	mPFS: 4,2 months; PFS6m: 41.8%	[64]
	BVZ + irinotecan + TMZ; (6 patients); BVZ + irinotecan; (1 patient); BVZ + CCNU; (1 patient)	Phase II	Relapsed or progressive HGG	mPFS: 15 weeks; mOS: 30 weeks	[66]

TMZ: temozolomide; mOS: median overall survival; OS1y: overall survival at 1 year; OS2y: overall survival at 2 years; OS3y: overall survival at 3 years; mPFS: median progression-free survival; PFS1y: progression-free survival at 1 year; PFS2y: progression-free survival at 2 years; SD: stable disease; EFS6m: event-free survival at 6 months; EFS12m: event-free survival at 12 months; EFS3y: event-free survival at 3 years; RT: radiotherapy; CT: chemotherapy; BVZ: bevacizumab; GBM: glioblastoma multiforme.