Boron Neutron Capture Therapy in Recurrent High-Grade Gliomas: Safety, Efficacy, and Pharmacokinetics From a Multicenter, Dose-Escalation Phase 1 Trial

초록

Purpose: Boron neutron capture therapy (BNCT) is an advanced radiation therapy delivering highly selective tumor cell destruction via localized fission reactions. This phase 1 study evaluated the safety and efficacy of BNCT using [B-10]L-4-boronophenylalanine (BPA) in patients with recurrent high-grade gliomas, mostly glioblastomas. Methods and Materials: A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose of BNCT across 3 planned cohorts (Dmax: 9, 11, and 13 Gy-Eq), with 3 additional subjects enrolled at any dose level where dose-limiting toxicity (DLT) occurred. DLT was defined as BNCT-related grade 3+ toxicities within 90 days posttreatment, with protocol-defined exclusions. Patients underwent a single session: intravenous BPA administration (500 mg/kg/3 h) and neutron irradiation 1 hour later. The primary endpoint was the recommended phase 2 radiation dose, based on DLT incidence. Secondary endpoint included safety, efficacy, and pharmacokinetics: treatment-emergent adverse events (TEAEs), progression-free survival, objective response rate, and overall survival (OS). Results: Six patients were treated between December 2022 and January 2024: 3 in the 9 Gy-Eq and 3 in the 11 Gy-Eq cohort. No DLTs or grade >= 4 TEAEs occurred. Two patients experienced grade 3 TEAEs (brain edema, seizure). Common adverse events were alopecia, aphasia, brain edema, and seizures. One serious adverse event (grade 3 seizure) was reported. Median follow-up was 9.03 months. Median progression-free survival was 1.87 months by response assessment in neuro-oncology; not reached by modified response assessment in neuro-oncology. Objective response was not observed. All patients survived to study completion; median OS not reached, maximum OS was 16.56 months. BPA pharmacokinetics were within expected ranges. The safety monitoring committee selected 11 Gy-Eq as the recommended phase 2 radiation dose, balancing tumoricidal effects with risks of necrosis and bevacizumab requirements. Conclusions: This study demonstrates the acceptable safety profile of BNCT and suggests potential survival benefits in recurrent highgrade glioma. However, given the limited sample size and follow-up period, extended observation is required to validate long-term efficacy and safety. (c) 2025 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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