Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy: a report of two cases

• Published in: Child's nervous system 2018-04, Vol.34 (4), p.605-610
• Main Authors: Upadhyaya, Santhosh A., Robinson, Giles W., Harreld, Julie H., Klimo, Paul D., Hoehn, Mary Ellen, Orr, Brent A., Qaddoumi, Ibrahim A.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brief Communication; Child, Preschool; Humans; Infant; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Mutation - genetics; Neurosciences; Neurosurgery; Optic Nerve Glioma - diagnostic imaging; Optic Nerve Glioma - drug therapy; Optic Nerve Glioma - genetics; Proto-Oncogene Proteins B-raf - genetics; Recovery of Function - drug effects; Recovery of Function - genetics; Treatment Outcome; Vemurafenib - therapeutic use
• ISSN: 0256-7040; 1433-0350
• DOI: 10.1007/s00381-018-3739-4

Background Despite appropriate therapeutic interventions, progressive optic pathway glioma (OPG) in children may result in loss of vision and other neurologic morbidities. Molecularly targeted therapy against the MAP kinase pathway holds promise in improving outcomes while resulting in lower treatment-related toxicities. We report two children with refractory OPG who had a substantial and early reversal of their neurologic deficits and an impressive imaging response of their tumor to BRAFV600E inhibition therapy. Methods Two children with OPG ( BRAFV600E -mutated pilocytic astrocytoma) who did not respond to at least one frontline therapy were treated with the oral BRAFV600E inhibitor vemurafenib. Results Both children had substantial visual compromise before start of therapy, with one child additionally having motor deficits. Both had an early improvement in their vision, and the second child showed a demonstrable improvement in motor weakness. This was accompanied by a decrease in tumor size, which was sustained at 6 months from therapy. Neither child had significant toxicities except for mild skin sensitivity to vemurafenib. Conclusions BRAFV600E inhibitor therapy can potentially reverse visual and neurologic decline associated with progressive OPG. The clinico-radiologic response appears to be prompt and marked. Ongoing clinical trials using BRAFV600E inhibitors can help confirm these early promising findings.