Natural History and Current Treatment Options for Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex

Subependymal giant cell astrocytoma (SEGA) is a benign brain tumor associated with tuberous sclerosis complex (TSC). Since there were some discrepancies in SEGA classification, in 2012, a consensus statement defined SEGA as a lesion at the caudothalamic groove with either a size of more than 1cm in any direction or a subependymal lesion at any location that has shown serial growth on consecutive imaging regardless of size. This pointed that the documented tumor growing is an important diagnostic feature. Currently, there are 2 therapeutic options: surgical and medical with mammalian target of rapamycin (mTOR) inhibitors. Neurosurgery should consider a localization and size of the tumor, presence of hydrocephalus and surgeon's experience. Patients who are not qualified for surgery and require therapeutic intervention are subjected to mTOR inhibitors therapy. Everolimus, one of the mTOR inhibitors, has been recently approved in the US and Europe for treatment of patients with TSC and SEGA. Treatment with everolimus results in a rapid initial reduction in tumor volume, followed by a phase of slower reduction or stabilization of residual mass. mTOR inhibitor dose de-escalation strategy seems to be also logical in long-term SEGA treatment to reduce the risk of adverse effects while maintaining the therapeutic effect. However, duration of the treatment and the efficacy of dose reduction are still questionable. Thus, this review covers the various approaches that are currently being made toward improving the outcome of management of SEGA among patients with TSC.