The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective.

BACKGROUND: Tuberous sclerosis (TSC) is a genetic multisystem disorder associated with hamartomas in several organs including subependymal giant cell tumors (SGCT). SGCT have the potential to grow and therefore to become symptomatic and are one of the main causes of death in TSC individuals. Surgical resection is the procedure of choice for SGCT. However, the discovery of mTOR pathway upregulation in TSC-associated tumors and recent evidence that mTOR inhibitors may induce regression of SGCT open up new treatment strategies. Based on a review of the currently available literature and on personal experience, current options for the management of TSC patients and appropriate indications, taking into account benefits and risks of surgery and pharmacotherapy, are discussed. DISCUSSION: An earlier diagnosis of SGCT in neurologically asymptomatic children may allow a precocious surgical removal of the tumor, thus minimizing surgery-related morbidity and mortality. Biologically targeted pharmacotherapy with mTOR inhibitors such as sirolimus and everolimus provides a safe and efficacious treatment option for patients with SGCT and has the potential to change the clinical management of these tumors. However, whether pharmacotherapy is sufficient to control growth or if it only delays the need for surgical removal of symptomatic SGCT remains unclear. Further studies are needed to determine the optimal levels of mTOR inhibitors that preserve maximal anti-tumor efficacy while minimizing side effects.