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

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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.

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Acknowledgements

The authors gratefully acknowledge Dr. Angela McArthur and Dr. Vani Shankar for the scientific editing of the manuscript.

Funding

This work was supported by grant CA21765 from the National Institutes of Health, an unrestricted grant from Research to Prevent Blindness (MEH), and ALSAC.

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Authors and Affiliations

  1. Department of Oncology, MS 260, Division of Neuro-Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Santhosh A. Upadhyaya, Giles W. Robinson & Ibrahim A. Qaddoumi

  2. Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Julie H. Harreld

  3. Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Paul D. Klimo Jr & Mary Ellen Hoehn

  4. Department of Neurosurgery, LeBonheur Children’s Hospital, Memphis, TN, USA

    Paul D. Klimo Jr

  5. Department of Ophthalmology & Pediatrics, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA

    Mary Ellen Hoehn

  6. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Brent A. Orr

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  1. Santhosh A. Upadhyaya
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  2. Giles W. Robinson
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  7. Ibrahim A. Qaddoumi
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Correspondence to Ibrahim A. Qaddoumi.

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The authors declare no conflict of interest.

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The study was approved by the institutional review board of St. Jude Children’s Research Hospital and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Written informed consent was obtained from the patient families for review and publication of this report and any accompanying images.

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Upadhyaya, S.A., Robinson, G.W., Harreld, J.H. et al. Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy: a report of two cases. Childs Nerv Syst 34, 605–610 (2018). https://doi.org/10.1007/s00381-018-3739-4

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