Supplementary Material for: Successful treatment with dabrafenib/trametinib of a malignantly transformed and metastasized BRAFV600E mutant pleiomorphic xanthoastrocytoma: a case report and review of the literature

Pleiomorphic xanthoastrocytoma (PXA) is considered a low grade glioma with a favorable prognosis following surgical resection. We present a case report of a BRAFV600E mutant malignantly transformed and disseminated PXA that was successfully treated with BRAF-/MEK-targeted therapy (dabrafenib/trametinib).
At the age of 16 years, our patient underwent an initial gross macroscopic resection of a right occipital PXA. Six months later, a reintervention for an asymptomatic tumor recurrence was performed; and complete resection was achieved. The patient was followed up by MRI for 14 years without arguments for recurrence. He was lost to follow-up thereafter. At the age of 38 years, he presented with a symptomatic local recurrence with extra-cerebral soft tissue extension for which a surgical resection was performed. Anatomopathological examination reported a grade 3 anaplastic PXA (aPXA); molecular analysis detected a BRAFV600E mutation. Three months later, before the initiation of radiotherapy, a local tumor recurrence was diagnosed for which he underwent a fourth surgical resection. Radiotherapy was performed following surgical debulking. One month after completion of radiotherapy, disease progression was documented including multiple sites of extra-cranial metastases (skeletal-, lung-, cervical lymph node and subcutaneous metastases). Systemic treatment with a combination of BRAF-/MEK-inhibitors (dabrafenib/trametinib) was initiated and resulted in a rapid and deep tumor response (partial response according to RECISTv1.1) and absence of BRAFV600E mutant ctDNA in plasma at 6 weeks after treatment initiation. A near-complete metabolic remission was documented on [18F]FDG PET/CT 3 months after starting systemic therapy.
In conclusion, we present a rare case of a malignant transformation and systemic dissemination of a BRAFV600E mutant PXA, occurring 20 year after the initial diagnosis. This case highlights the importance of long-term follow-up of patients diagnosed with these rare central nervous system (CNS) tumors that initially are considered benign, and also illustrates that BRAF/MEK inhibition can be an effective therapy for BRAFV600E -mutated PXA, underscoring the importance of performing molecular genetic profiling of these tumors.