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Efficacy of Dabrafenib for three children with brainstem BRAFV600E positive ganglioglioma

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A Correction to this article was published on 25 November 2019

This article has been updated

Abstract

Purpose

Children with unresectable brainstem-infiltrated ganglioglioma have poor progression-free survival when treated with conventional chemotherapy and radiation regimens. The BRAFV600E mutation occurs in a large number of gangliogliomas, making them amenable for targeted therapy using mutation-specific kinase inhibitors. However, limited data exists on the effectiveness and best treatment duration of these inhibitors in this tumor setting.

Method

Retrospective description of three cases of childhood brainstem ganglioglioma with BRAFV600E mutation treated in the long-term with Dabrafenib, a specific BRAFV600E kinase inhibitor.

Results

Dabrafenib resulted in rapid tumoral regression and significant and durable clinical and radiological improvement. However, all patients had rapid clinical and radiological relapse within days to weeks following treatment discontinuation but showed similar rapid and sustained therapeutic response when Dabrafenib was re-introduced. This targeted therapy has been well tolerated despite its long-term use of 4.8 to 5.5 years in the three patients.

Conclusion

Dabrafenib is effective and seemingly safe and well tolerated in our three patients. We observed sustained chemosensitivity even when re-introducing this kinase inhibitor after its discontinuation after 2 years of therapy. These cases indicate the need to re-evaluate the timing and means of Dabrafenib discontinuation in pediatric patients with BRAFV600E mutated gangliogliomas and better assess the future implications of its long-term use.

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Change history

  • 25 November 2019

    In the original article, the author names were published incorrectly. The names are correct in this publication.

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Authors and Affiliations

  1. Department of Medicine, Laval University, Québec, Canada

    Laflamme Philippe

  2. Department of Medicine, Montreal University, Montreal, Canada

    Kondyli Maria

  3. Division of Neurosurgery, Department of Pediatric Surgery, Montreal Children’s Hospital, McGill University Health Center, Montreal, Canada

    Aljared Tariq, Farmer Jean-Pierre & Roy W. Dudley

  4. Department of Pathology, McGill University Health Center, Montreal, Canada

    Miconiatis Sofia

  5. Department of Medical Imaging, Montreal Children’s Hospital, McGill University Health Center, Montreal, Canada

    Saint-Martin Christine

  6. Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada

    Perreault Sébastien

  7. Department of Pediatrics, McGill University and McGill University Heath Centre Research Institute, Montreal, Canada

    Jabado Nada

  8. Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Québec-Université Laval, Québec, Canada

    Larouche Valérie

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  1. Laflamme Philippe
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  2. Kondyli Maria
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  6. Farmer Jean-Pierre
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Philippe, L., Maria, K., Tariq, A. et al. Efficacy of Dabrafenib for three children with brainstem BRAFV600E positive ganglioglioma. J Neurooncol 145, 135–141 (2019). https://doi.org/10.1007/s11060-019-03280-2

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  • DOI: https://doi.org/10.1007/s11060-019-03280-2

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