Safety and effectiveness of mTOR inhibitor treatment for SEGAs in TSC
Safety and effectiveness of mTOR inhibitor treatment for SEGAs in TSC
About this study
This study looked at the long-term use of the mTOR inhibitor (mTORi) medicines everolimus and sirolimus for treating subependymal giant cell astrocytomas (SEGAs) in people with TSC.
SEGAs are slow-growing brain tumours that develop near the fluid pathways inside the brain. If they grow too large, they can lead to hydrocephalus, a dangerous build-up of fluid in the brain that increases pressure and can cause headaches, sickness, vision problems, and, if untreated, can be life-threatening. Surgery used to be the main treatment, but it can be risky and the SEGAs can regrow. mTOR inhibitors offer a non-surgical way to shrink or control SEGAs. This research followed people for more than 15 years on average, making it one of the longest studies of this treatment in TSC.
How the study was conducted
Researchers at Cincinnati Children’s Hospital Medical Centre reviewed the medical records of 25 people with TSC who had taken part in earlier mTORi clinical trials for SEGAs and continued to be followed at the centre. All had at least 10 years of follow-up after starting treatment. Participants had regular MRI scans to track SEGA size, along with monitoring for side effects. Both everolimus and sirolimus were used, with most participants taking everolimus. Researchers looked at whether SEGAs stayed the same size, shrank, or grew, and monitored both short-term and long-term side effects.
Outcomes of the study
Over the course of the follow-up, most participants experienced good control of their SEGAs. In 76% of cases, the tumours either remained stable in size or became smaller, and only one person required further surgery for SEGA growth during the study period. Importantly, no participants developed hydrocephalus needing urgent treatment after starting mTOR inhibitor therapy, a major change from the past when many people required a shunt (a device to drain excess fluid from the brain) to relieve the pressure caused by hydrocephalus.
Short-term side effects of the treatment were generally mild, with mouth ulcers being the most common and affecting about a third of participants. Long-term side effects occurred in around two-thirds of the group and often appeared many years after treatment began. The most common were high cholesterol, affecting 40% of participants, and type 2 diabetes, diagnosed in roughly 25% of participants. Osteoporosis (weakened bones) occurred in a few participants, although this may have been linked to other medicines such as anti-seizure drugs rather than the mTOR inhibitors themselves.
All participants in the study had a history of epilepsy, but seizure control varied. Many were able to manage on fewer anti-seizure medicines than before taking mTORi, and some reported fewer seizures overall. TSC-associated neuropsychiatric disorders (TAND) such as intellectual disability, autism, anxiety, and obsessive-compulsive disorder were also common in this group, showing that while SEGAs can be brought under control, other aspects of TSC often still need ongoing care.
Conclusions of the study
Long-term mTOR inhibitor treatment for SEGAs in TSC is effective at keeping tumours stable and reducing the need for brain surgery. The treatment is generally well tolerated, though ongoing monitoring is essential because some side effects – like high cholesterol or diabetes – can emerge many years later. Most of the side effects can be managed with medication or lifestyle changes.
Implications of the study
For people with TSC who develop SEGAs, mTOR inhibitors may offer a safe and effective long-term alternative to surgery. The treatment can prevent dangerous complications like hydrocephalus, reduce the need for invasive procedures, and maintain quality of life. However, because some side effects may only appear after many years, long-term follow-up with regular checks on cholesterol, blood sugar, bone health, and blood pressure is important. The findings also raise important questions for future research, such as whether starting mTORi treatment earlier could improve seizure control or cognitive outcomes in TSC.
DISCLAIMER
This information is intended to provide some insights into recent TSC-related research. It is not intended to, and it should not, constitute medical or other advice. Readers are warned not to take any action without first seeking medical advice.
Becker LL, Agricola K, Ritter DM, Caré MM, Krueger DA, Franz DN. Long-Term Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Treatment for Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis. Pediatr Neurol. 2025 Jul;168:90-95. doi: 10.1016/j.pediatrneurol.2025.04.007. Epub 2025 Apr 21. PMID: 40393382.
Full paper available at: 10.1016/j.pediatrneurol.2025.04.007