Subependymal Giant Cell Astrocytomas (SEGAs): a Model of Targeting Tumor Growth and Epilepsy

Abstract

Subependymal giant cell astrocytomas (SEGAs) are grade I astrocytic tumors according to WHO 2016, mainly associated to tuberous sclerosis complex. They are rare and achievements in their management are often the result of small series and case reports. The main purpose of this review was to summarize recent developments in diagnosis and treatment of SEGAs. The role of treatment with mTOR inhibitors has been confirmed through many studies in the last decade. New treatment options for patients with contraindication to surgery have been proposed, like Gamma Knife and laser interstitial thermal therapy (LITT). Furthermore, more recent preclinical studies, investigating MAPK/ERK pathways, CK2 protein (casein kinase), and metalloproteinases and their tissue inhibitors (TIMPs), have been published, suggesting new pharmacological treatments. This review is focused on natural history, pathogenesis, diagnosis, and treatment of SEGAs, with an update of the more recent developments. SEGAs are mainly associated to tuberous sclerosis complex, while in sporadic forms to mutations in genes TSC1 or TSC2 limited to the tumor. TSC2 mutation leads to higher incidence of SEGAs, earlier onset and more aggressive course. Diagnosis is made by MRI and by criteria defined in the EXIST-1 study. Treatment options are surgery and pharmacological treatment with mTOR inhibitors. LITT shows promising results. Besides tumor grade, SEGAs show a continuous tendency to growth after incomplete resection or withdrawal of mTOR inhibitors. Preclinical studies have explored novel treatment options, but they need to be confirmed in clinical trials.