Significant clinical and radiologic response to targeted therapy in pediatric cervicomedullary low-grade gliomas harboring the BRAFV600E mutation.

purposeChildren with unresectable cervicomedullary tumors (CMTs) demonstrate poor progression-free survival when treated with conventional chemotherapy and radiotherapy. The BRAFV600E mutation, commonly identified in low-grade gliomas, represents a therapeutic target for mutation-specific kinase inhibitors. This study aims to emphasize the potential role of BRAF inhibitors as upfront targeted therapy in selected tumors where surgical resection is not feasible.

methodsA retrospective analysis was conducted on four pediatric patients with unresectable cervicomedullary low-grade gliomas harboring the BRAFV600E mutation. All patients were treated with the BRAF inhibitor dabrafenib, either as first-line or second-line therapy.

resultsDabrafenib was administered as first-line therapy in two patients and as second-line therapy in two others. All patients experienced rapid tumor regression with significant and durable clinical and radiologic responses. Three patients tolerated long-term therapy (up to 9 years) without significant toxicity. One patient discontinued treatment after 1 year due to a serious adverse event, which resolved upon withdrawal of therapy.

conclusionDabrafenib demonstrated clinical and radiographic efficacy and was generally well tolerated in pediatric patients with unresectable BRAFV600E-mutant CMTs. These findings suggest that upfront BRAF inhibition may serve as a viable therapeutic alternative to conventional chemotherapy, radiotherapy, or attempted resection in selected cases. Further prospective studies are warranted to define the optimal timing, duration, and long-term safety of targeted therapy in this population.