Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy

a report of two cases

Santhosh A. Upadhyaya, Giles W. Robinson, Julie H. Harreld, Paul Klimo, Mary Ellen Hoehn, Brent A. Orr, Ibrahim A. Qaddoumi

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)605-610
Number of pages6
JournalChild's Nervous System
Volume34
Issue number4
DOIs
StatePublished - Apr 1 2018

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Optic Nerve Glioma
Therapeutics
Nervous System
Astrocytoma
Neurologic Manifestations
Neoplasms
Phosphotransferases
Clinical Trials
Morbidity
Skin

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy : a report of two cases. / Upadhyaya, Santhosh A.; Robinson, Giles W.; Harreld, Julie H.; Klimo, Paul; Hoehn, Mary Ellen; Orr, Brent A.; Qaddoumi, Ibrahim A.

In: Child's Nervous System, Vol. 34, No. 4, 01.04.2018, p. 605-610.

Research output: Contribution to journalArticle

Upadhyaya, Santhosh A. ; Robinson, Giles W. ; Harreld, Julie H. ; Klimo, Paul ; Hoehn, Mary Ellen ; Orr, Brent A. ; Qaddoumi, Ibrahim A. / Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy : a report of two cases. In: Child's Nervous System. 2018 ; Vol. 34, No. 4. pp. 605-610.
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