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Significant response to targeted therapy for Cervico-Medullary pediatric low grade glial tumors with BRAFV600E mutation
  • +6
  • Gadi Abebe Campino,
  • Shani Caspi,
  • Shlomi Constantini,
  • Shai Shrot,
  • Jonathan Roth,
  • Dvora Nass,
  • Michal Lurye,
  • Amos Toren,
  • Michal Yalon
Gadi Abebe Campino
Sheba Medical Center

Corresponding Author:[email protected]

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Shani Caspi
Sheba Medical Center
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Shlomi Constantini
Dana-Dwek Children's Hospital
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Shai Shrot
Sheba Medical Center
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Jonathan Roth
Dana-Dwek Children's Hospital
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Dvora Nass
Sheba Medical Center
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Michal Lurye
Sheba Medical Center
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Amos Toren
Sheba Medical Center
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Michal Yalon
Sheba Medical Center
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Abstract

Purpose: Children with unresectable cervico-medullary low-grade glial tumors (CMTs) have poor progression-free survival when treated with conventional chemotherapy and radiation. The BRAFV600E mutation occurs in many low-grade glial tumors that are amenable for targeted therapy using mutation-specific kinase inhibitors. However, these inhibitors’ effectiveness and best treatment duration in these tumors setting are not defined. Method: Retrospective description of three cases of childhood cervico-medullary low-grade tumor with BRAFV600E mutation and their response to BRAF inhibitor therapy with Dabrafenib. Results: Dabrafenib therapy was provided as first line for two patients and second line for one patient with CMTs. All patients experienced rapid tumor regression and significant and durable clinical and radiological improvement. The targeted therapy was tolerated well in two patients despite the long-term use of 3-5 years, while one patient stopped therapy after 1 year due to serious adverse event that was reversible upon discontinuing therapy. Conclusion: Dabrafenib was effective and well-tolerated in two of the three patients. We observed clinical and radiological response that demonstrates the role of targeted therapy as alternative for adjuvant chemotherapy and radiation in BRAFV600E unresectable tumors. These cases indicate the need to re-evaluate the therapeutic approach in children with CMT, the early use of Dabrafenib and the treatment duration and to explore the possible adverse and late effects of this promising therapy.