Peer-reviewed article
LGG-03. LONG-TERM FOLLOW UP OF TARGETED THERAPY IN PEDIATRIC LOW-GRADE GLIOMAS: THE DANA-FARBER/BOSTON CHILDREN’S EXPERIENCE
Tsai J, Vogelzang J, Sousa C, Yeo K, Ligon K et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case series describing the clinical outcomes of 49 children with low-grade brain tumors treated with targeted cancer therapies at a Boston hospital between 2010 and 2020. The study reviews how long children survived and progressed after receiving drugs like dabrafenib and everolimus. Event-free survival rates declined over time, with 58% of children free from progression at 1 year, dropping to 27% at 5 years. The research aims to better understand how these targeted drugs affect the natural progression of these tumors.
Key points
- 49 pediatric patients with low-grade gliomas received targeted therapies; 25% received it as first-line treatment
- 1-year, 3-year, and 5-year event-free survival rates from treatment initiation were 58.0%, 32.2%, and 26.9% respectively
- Median duration of targeted therapy was 0.79 years; median time to subsequent therapy was 0.2 years
- Reasons for stopping treatment included toxicities, disease progression, and planned completion of therapy
- All patients receiving BRAF inhibitors had the BRAF V600E mutation, suggesting treatment was molecularly guided
Limitations
This is a retrospective clinical review at a single center with a small sample size and no comparison group, so causality cannot be established. The study cannot determine whether improved survival or progression outcomes are specifically due to the targeted therapies versus the natural history of these tumors.
Abstract
Abstract Background Pediatric low grade gliomas (pLGGs) are the most common central nervous system (CNS) tumor in children and characterized by alterations in the MAPK pathway. Standard of care is not well defined, and treatment has evolved over the last decade to include molecular targeted therapies. The impact of targeted agents on the natural history of pLGGs remains unknown. We present a retrospective review of patients receiving targeted agents integrated with molecular profiling. Methods We performed an IRB-approved, retrospective chart review of pLGGs treated with off-label use of dabrafenib, vemurafenib, everolimus, and trametinib at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center from 2010 to 2020. Results Forty-nine patients were identified (dabrafenib n=9, everolimus n=27, trametinib n=10, and vemurafenib n=3). All patients receiving BRAF inhibitors harbored BRAF V600E mutation. Targeted agent was used as first-line therapy for 25% of patients, while for 31% of patients, targeted agent was second-line therapy. The median time from diagnosis to targeted therapy initiation was 4.76 years (0.10 – 23.77), median duration of targeted therapy was 0.79 years (0.01 – 4.87), median time to subsequent therapy post first-line targeted therapy was 0.2 years (0.01 – 3.33), and overall median follow-up for the entire cohort was 3.09 years (0.36 – 11.87). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation was 58.0%, 32.2%, and 26.9%, respectively. Survival analyses by molecular subgroup and agent were performed. Reasons for cessation of targeted therapy included toxicities, progression, and/or planned end of therapy. Conclusions Further efforts are ongoing to perform volumetric analysis of growth rates before, during, and after treatment. While targeted molecular therapies show great promise, it will be critical to understand how these agents alter the natural history of pLGGs, particularly in the context of genomic profiling.