Patients with primary brain tumors often experience seizures, which can be the presenting symptom or occur for the first time at any point along the illness trajectory. In addition to causing morbidity, seizures negatively affect independence and quality of life in other ways, for example, by leading to loss of driving privileges. Long-term therapy with antiepileptic drugs (AEDs) is the standard of care in brain tumor patients with seizures, but the role of prophylactic AEDs in seizure-naive patients remains controversial. In this article, experts in the field discuss the issues of AED efficacy and toxicity, and explain their differing recommendations for routine use of prophylactic AEDs.

Purpose of Review Leptomeningeal disease (LMD) is a devastating complication of advanced metastatic cancer associated with a poor prognosis and limited treatment options. This study reviews the current understanding of the clinical presentation, pathogenesis, diagnosis, and treatment of LMD. We highlight opportunities for advances in this disease. Recent Findings In recent years, the use of soluble CSF biomarkers has expanded, suggesting improved sensitivity over traditional cytology, identification of targetable mutations, and potential utility for monitoring disease burden. Recent studies of targeted small molecules and intrathecal based therapies have demonstrated an increase in overall and progression-free survival. In addition, there are several ongoing trials evaluating immunotherapy in LMD. Summary Though overall prognosis of LMD remains poor, studies suggest a potential role for soluble CSF biomarkers in diagnosis and management and demonstrate promising findings in patient outcomes with targeted therapies for specific solid tumors. Despite these advances, there continues to be a gap of knowledge in this disease, emphasizing the importance of inclusion of LMD patients in clinical trials.

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BACKGROUND Up to 65% of anaplastic pleomorphic xanthoastrocytomas (A-PXA) harbor the BRAFV600E oncogene. Trials and case series have demonstrated that BRAF-mutant gliomas, including A-PXAs, can be responsive to the first generation BRAF inhibitors dabrafenib and vemurafenib, with an ORR ranging from 26–43%. The second generation BRAF/MEK inhibitor combination encorafenib/binimetinib improves systemic outcome in melanoma patients, has better tolerability, and may have better intracranial activity compared to first generation drugs. METHOD We review the three patients with BRAFV600E A-PXA treated with encorafenib/binimetinib in our practice. RESULTS Two patients were diagnosed with A-PXA in 2014 and one in 2013. The presence of BRAFV600E was confirmed by molecular testing. All patients have received prior surgery, chemotherapy, and radiation and were at a recurrence when BRAF/MEK inhibition was initiated. One patient had CR after 2 months on treatment and remains in CR at 1-year. One patient, who is also receiving bevacizumab, has a PR, with continued clinical and imaging improvement at 6 months. Our third patient had a PR at 2 months and remains on therapy, currently 3 months post-initiation. All 3 patients report improvement in symptoms. The patient who has been on treatment for 1 year experienced rapid onset bilateral multifocal sub-retinal fluid collections followed by rapid resolution, without intervention, within days of starting treatment. This patient has also had mild decrease in EF over time. We will present continued follow up. CONCLUSIONS Encorafenib/binimetinib appears feasible, with 3 of out 3 patients with BRAFV600E A-PXA demonstrating radiographic response; 2 of these patients have durable responses. We stress the importance of a clear lab, cardiac, ophthalmologic, and dermatologic monitoring regimen as side effects can be rapid and severe. Prospective studies with encorafenib/binimetinib in BRAF-mutant primary CNS tumors are underway, and we eagerly anticipate their RESULTS: