Neuro-oncology
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Multicenter Study
Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma.
No proven effective medical therapy for surgery and radiation-refractory meningiomas exists. Sunitinib malate (SU011248) is a small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor, abundant in meningiomas. ⋯ Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.
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According to the Response Assessment in Neuro-Oncology criteria, new enhancement within the radiation field on contrast enhanced T1-weighted images within 12 weeks after completion of radiotherapy should not qualify for progressive disease, since up to 50% of these cases may be pseudoprogression (PsP). To validate this concept, we assessed incidence and overall survival (OS) of patients with suspected and confirmed PsP dependent on different time intervals and definitions of PsP. ⋯ This series challenges the current concept of PsP. Even though we could confirm a prolonged OS of patients with PsP, the incidence of PsP was lower than reported previously and extended beyond 12 weeks.
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Multicenter Study
A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a pediatric brain tumor consortium report.
A phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic parameters and extent of PARP inhibition in peripheral blood mononuclear cells (PBMCs) following veliparib. ⋯ Veliparib and TMZ at the RP2D were well tolerated in children with recurrent brain tumors. A phase I/II trial to evaluate the tolerability and efficacy of veliparib, TMZ, and radiation in children with newly diagnosed brainstem gliomas is in progress.
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Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. ⋯ Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.