Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility

Abstract

Background Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi. Methods We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi. Results In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi. Conclusions The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.

Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age

“…mTOR inhibitors were recently approved in the EU, USA, and Japan [8]. Besides focal-onset seizures, everolimus is currently approved for treating SEGA and LAM and used as an off-label treatment for CR reduction [9][10][11][12][13]. Sirolimus is approved only as LAM therapy in patients with TSC, while its impact on seizure frequency is not yet determined.…”

The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation

“…New rapamycin analogs (Rapalogs) have been developed for TSC patients and other diseases with mTORC1 hyperactivation. Everolimus, the hydroxyethyl ester of rapamycin, was successful in shrinking SEGAs [11,12]. Long-term Everolimus treatment efficiently reduced SEGAs and prevented new SEGAs formation [13].…”