LOW-GRADE GLIOMA COMBINATION CHEMOTHERAPY MAY BE EFFECTIVE IN BRAF V600E CODON-MUTATED OPTIC PATHWAY GANGLIOGLIOMAS

INTRODUCTION: Gangliogliomas (GG) are low-grade mixed glial/neuronal tumors typically seen in children and young adults. They commonly arise in the cerebrum, cerebellum and brainstem and are often associated with seizures. Management is typically surgical. Adjuvant radiation therapy is occasionally used, but primary treatment with chemotherapy is not considered standard. Very rarely, GG involves the optic pathway, with this location being rarely amenable to surgery, threatens vision and mandates creative treatment approaches. Many GG have mutations in the BRAF proto-oncogene, critical for regulating the MAP kinase/ERKs signaling pathway which affects cell division and differentiation. METHODS/RESULTS: A 4-year-old boy presented with a many-year history of abnormal eye movements and progressive visual decline. Ophthalmologic examination revealed esotropia, optic atrophy and poor visual acuity. MRI scanning revealed an extensive bilateral infiltrative tumor involving the optic pathway, hypothalamus, thalami, midbrain and temporal lobes. An image-guided stereotactic biopsy revealed a typical WHO grade 1 ganglioglioma and tumor cell pyrosequencing revealed a BRAF codon 600 (V600E) mutation. There was no clinical or imaging evidence of NF1. Given the tumor’s unresectability and the reticence to use ionizing radiation therapy at such a young age, combination chemotherapy using carboplatin and vincristine was started. Tumor extent and contrast enhancement decreased dramatically during the one year chemotherapy journey and ophthalmologic parameters stabilized. CONCLUSIONS: The management of GG is typically surgical, with careful use of radiation therapy for select circumstances. Chemotherapy is not typically considered an effective therapy. However, this case suggests that GG can be chemosensitive, to standard low-grade glioma chemotherapy. The presence of the BRAF V600E mutation is common in GG and may afford a therapeutic management strategy for select cases, using BRAF inhibitors such as vemurafenib and dabrafenib. We recommend the ongoing reporting of novel treatment strategies for challenging-site GG and suggest BRAF analysis for such tumors.