ID #477 mTOR Inhibitors as a Therapeutic Alternative for Pediatric Neurofibromatosis Type 1-Associated Central Nervous System Tumors in a Resource-Limited Setting
Juliana Barreto, Lilian Cristofani, Katharina Rodrigues, Rubens Bombardi Neto, Angelica Lucia Flores, Mariana Komatsu, Vitor Yamaki, Felipe Sanders, Jose Erasmo Col Lucio, Leandro Lucato, Yuri Casal, Vicente Odone Filho, Alessandra AzambujaAbstract
Introduction
In Neurofibromatosis type 1 (NF1), central nervous system (CNS) tumors, particularly low-grade gliomas, often have an indolent course. However, tumor progression may compromise neurological function, making disease stabilization and functional preservation key goals. While MEK inhibitors, such as selumetinib, have demonstrated clinical benefit, limited access in low- and middle-income countries restricts their use, making mTOR inhibitors an alternative despite limited data. This study aimed to evaluate outcomes of mTOR inhibitor therapy in pediatric patients with NF1-associated CNS tumors.
Materials and Methods
This retrospective, single-center observational study reviewed medical records of pediatric patients (<18 years) with NF1 and CNS tumors treated with mTOR inhibitors between 2016 and 2025. Data collected included treatment modalities, radiological response or stability, functional neurological outcomes, treatment duration, and toxicity.
Results
Nineteen pediatric patients with NF1 were analyzed, of whom 16 (84.2%) had CNS tumors. Among these, ten patients received mTOR inhibitors (everolimus, n = 6; sirolimus, n = 3; sequential everolimus/sirolimus, n = 1), and four received concomitant chemotherapy due to disease severity at diagnosis. Over a median follow-up of 17 months (range 6–113), disease stability was observed in 9 of 10 patients (90%) treated with mTOR inhibitors; one death occurred in a patient receiving everolimus, not related to treatment toxicity. Reported toxicities included stomatitis/aphthae (20%), headache (20%), hyperlipidaemia (10%), and febrile neutropenia (10%) in a patient receiving chemotherapy. All patients remained on continuous mTOR inhibitor therapy.
Conclusion
In our resource-limited setting with restricted access to first-line targeted therapies, mTOR inhibitors were associated with high rates of disease stability and predominantly manageable toxicity. Their cytostatic effect supports sustained tumor control with preservation of neurological function. These findings reinforce mTOR inhibitors as a safe and feasible therapeutic option when MEK inhibitors are unavailable.