Laflamme Philippe1, Kondyli Maria2, Aljared Tariq3, Miconiatis Sofia4, Saint-Martin Christine5, Farmer Jean-Pierre3, Roy W Dudley3, Perreault Sébastien6, Jabado Nada7, Larouche Valérie8. 1. Department of Medicine, Laval University, Québec, Canada. 2. Department of Medicine, Montreal University, Montreal, Canada. 3. Division of Neurosurgery, Department of Pediatric Surgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada. 4. Department of Pathology, McGill University Health Center, Montreal, Canada. 5. Department of Medical Imaging, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada. 6. Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada. 7. Department of Pediatrics, McGill University and McGill University Heath Centre Research Institute, Montreal, Canada. 8. Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Québec-Université Laval, Québec, Canada. valerie.larouche@chudequebec.ca.
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.
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.
Entities:
Keywords:
BRAFV600E; Central nervous system; Children; Dabrafenib; Ganglioglioma
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