Significant response to targeted therapy for Cervico-Medullary pediatric
low grade glial tumors with BRAFV600E mutation
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.