Pilocytic astrocytomas (PAs) are low-grade gliomas that constitute approximately 20% of all pediatric central nervous system (CNS) tumors.1 PAs in children are often associated with genetic alterations, which result in constitutive activation of BRAF or the downstream MAPK pathway.2 The most common activating events in PAs are the fusion of KIAA1549 and BRAF resulting in an activated oncogene (65%–90%),3,4 and a single nucleotide variant in BRAF resulting in a valine-to-glutamate substitution in amino acid codon 600 (BRAF p.Val600Glu) (6%–9%).2,5 BRAF p.Val600Glu is frequently observed in other low-grade gliomas, including pleomorphic xanthoastrocytomas (50%–66%) and gangliogliomas (20%).6
Patients with PAs typically have 10-year survival rates of 80% to 100% with complete resection. However, tumors located along the midline and disseminated PAs have a suboptimal response to conventional chemotherapy and a relatively poor prognosis.7 There are several reports of successful treatment of low- and high-grade gliomas with BRAF inhibitors (vemurafenib and dabrafenib).8–13 There is only a single report of 2 patients with PAs who were treated with trametinib, a MAPK pathway inhibitor,5 and no reports on MAPK pathway–targeted therapy for disseminated PAs. This report presents a series of 5 patients with progressive disseminated PA, and discusses the clinical response to targeted molecular therapy in 2 patients.
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