LG-20CAUTION IN THE USE OF BRAF INHIBITORS IN CHILDHOOD BRAIN TUMORS WITH BRAF V600E MUTATION

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a grade 2 glioma of adolescents and young adults. Seventy percent of PXAs carry a BRAF V600E mutation. We describe a 14 year old prepubertal girl with a centrally located, large, calcified tumor in the third ventricle, left thalamus and midbrain thatwasunresectable. Biopsy revealed a PXA with the BRAF mutation. Initial observation for 6 months showed progressive tumor growth and we started the BRAF inhibitor vemurafenib which we received compassionately at a dose of 555mg/m2 twice a day as recommended. MRI after 2 months showed initial very mild decrease in tumor size followed by a further 10 months of tumor stabilization. Side effects including rash and arthralgia were mild and manageable. After 1 year we elected to stop treatment. Three weeks later she presented with drowsiness and acute onset psychosis. MRI showed immense tumor growth in comparison to theMRIfrom4weeks previously, inparticular of solid enhancing elements. Rebiopsy revealed a grade 2 PXA similar to the initial sample. Pediatric oncologists should be aware of this “rebound phenomenon” when deciding to stop treatment with BRAF inhibitors. In metastatic melanoma in adults, BRAF inhibitors are stopped only when resistance develops and disease progresses. In children with gliomas it may be difficult to know when to stop and it may well be that treatment is “lifelong”. Caution should be used in starting therapy with these new drugs since long term information is still lacking.