title: Report of effective trametinib therapy in 2 children with progressive hypothalamic optic pathway pilocytic astrocytoma: documentation of volumetric response.
abstract: Brain tumors are the most common solid tumor in childhood, and astrocytomas account for the largest proportion of these tumors. Increasing sophistication in genetic testing has allowed for the detection of specific mutations within tumor subtypes that may represent targets for individualized tumor treatment. The mitogen-activating protein kinase (MAPK) pathway and, more specifically, BRAF mutations have been shown to be prevalent in pediatric pilocytic astrocytomas and may represent one such area to target. Herein, the authors describe 2 cases of inoperable, chemotherapy-resistant pediatric pilocytic astrocytomas with a documented response to trametinib, an MAPK pathway inhibitor. While these cases were not treated in the setting of a clinical trial, their data support further ongoing clinical trial investigation to evaluate the safety and efficacy of this agent in pediatric low-grade gliomas.
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Catherine
authors.initials: C
authors.lastname: Miller
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Daniel
authors.initials: D
authors.lastname: Guillaume
authors.affiliation: Radiation Oncology.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dusenbery
authors.affiliation: Pathology, and.
authors.forename: H Brent
authors.initials: HB
authors.lastname: Clark
authors.affiliation: Pediatric Hematology/Oncology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Christopher
authors.initials: C
authors.lastname: Moertel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000000981:diagnostic imaging* / Q000188:drug therapy; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D007223:Infant; D019574:Optic Nerve Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009929:Organ Size; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib
keywords: BRAF mutation; CNS = central nervous system; MAPK = mitogen-activating protein kinase; MAPK pathway; astrocytoma; oncology; pediatric; trametinib