BRAF/MEK double blockade in refractory anaplastic pleomorphic xanthoastrocytoma

A 32-year-old woman was diagnosed in February 2012 with a grade II pleomorphic xanthoastrocytoma (PXA) of the right parietal lobe. A complete excision was performed, followed by tumor bed irradiation (66 Gy). A local relapse occurred in September 2013, for which a partial resection was performed, confirming a grade II PXA. Immunohistochemical analysis indicated the presence of a BRAFV600E mutated protein, and combined treatment with vemurafenib and bevacizumab was initiated. A partial response was rapidly obtained, sustained for 12 months. In June 2015, a third surgery was performed for an extended relapse invading the right cerebral hemisphere. Histopathologic examination revealed anaplastic (grade III) PXA and confirmed the presence of the BRAFV600E mutation (figure, A and B). After unsuccessful treatment with bevacizumab and lomustine, tumor treating fields therapy was applied between August and December 2015. Treatment was complicated by severe skin toxicity, with progressive appearance of a 4-cm scalp wound. Concurrently, the patient developed a severe left hemiparesis with ataxia, hemispatial neglect, and central facial palsy. MRI revealed major disease progression. The patient was subsequently referred to our institution. Acknowledgment: The authors thank the patient and her family for consent to publish this report and Simon Rhead and Anna Patrikidou for English editing.