Accelerator-based BNCT for patients with recurrent glioblastoma: a multicenter phase II study

Abstract Background Boron neutron capture therapy (BNCT) utilizes tumor-selective particle radiation. This study aimed to assess the safety and efficacy of accelerator-based BNCT (AB-BNCT) using a cyclotron-based neutron generator (BNCT 30) and 10B-boronophenylalanine (SPM-011) in patients with recurrent malignant glioma (MG) (primarily glioblastoma [GB]). Methods This multi-institutional, open-label, phase II clinical trial involved 27 recurrent MG cases, including 24 GB cases, who were enrolled from February 2016 to June 2018. The study was conducted using the abovementioned AB-BNCT system, with 500 mg/kg SPM-011 (study code: JG002). The patients were bevacizumab-naïve and had recurrent MG after standard treatment. The primary endpoint was the 1-year survival rate, and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results were compared to those of a previous Japanese domestic bevacizumab trial for recurrent GB (JO22506). Results The 1-year survival rate and median OS of the recurrent GB cases in this trial were 79.2% (95% CI: 57.0–90.8) and 18.9 months (95% CI: 12.9–not estimable), respectively, whereas those of JO22506 were 34.5% (90% CI: 20.0–49.0) and 10.5 months (95% CI: 8.2–12.4), respectively. The median PFS was 0.9 months (95% CI: 0.8–1.0) by the RANO criteria. The most prominent adverse event was brain edema. Twenty-one of 27 cases were treated with bevacizumab following progressive disease. Conclusions AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG. AB-BNCT may increase the risk of brain edema due to re-irradiation for recurrent MG; however, this appears to be controlled well with bevacizumab.