Dose Escalation with Intensity-Modulated Proton Therapy for Patients with High-Risk Meningiomas – Results from a Phase I Trial

作者：Felix Ehret, Nora Horick, Beow Y. Yeap, William T. Curry, Brian Nahed, Juliane Daartz, Jason M. Johnson, Samir A. Dagher, Shaan M. Raza, Franco DeMonte, Debra N. Yeboa, Todd A. Swanson, Mary Frances McAleer, Peggy Leland, Susan L. McGovern, Helen A. Shih · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-25-3856 · 研究领域：Meningioma and schwannoma management、Brain Metastases and Treatment、Head and Neck Surgical Oncology

BACKGROUND: Outcomes for grade 2 and 3 meningiomas are poor. A few studies suggest a benefit from radiation therapy dose escalation. This trial evaluates the safety and efficacy of dose escalation with intensity-modulated proton therapy (IMPT) for grade 2 and 3 meningiomas. METHODS: This prospective single-arm phase 1 trial enrolled patients with grade 2 meningioma with residual disease or recurrence, or patients with grade 3 meningioma after gross total resection. Patients underwent dose-escalated IMPT to 66 Gy (relative biological effectiveness, RBE) for grade 2 gross disease and 63 Gy(RBE) for grade 3 tumor beds. The primary endpoint was acute dose-limiting toxicity (DLT). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and late toxicity. RESULTS: Twenty-one patients with 16 grade 2 and five grade 3 meningiomas were enrolled and treated between 2016 and 2023. The median clinical and radiographic follow-up periods were 3.4 and 3.2 years, respectively. No DLT was observed. Five new late grade 3 toxicities occurred in four patients. Three treatment failures were observed in two grade 2 and one grade 3 tumors. Two deaths occurred in patients with grade 2 meningiomas. The 1-, 2-, and 3-year PFS rates were 100%, 95.0%, and 88.2%, respectively. The corresponding OS rates were 100%, 95.0%, and 95.0%, respectively. CONCLUSIONS: This first prospective trial investigating dose-escalated IMPT for high-grade meningiomas demonstrated a favorable earl...