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.

Translational Evaluation of a Dodecaborated Albumin Conjugate With Maleimide as a Boron Delivery System for a Neutron Capture Reaction to an F98 Rat Glioma Model

“…For a long time now, a wide variety of boron delivery compounds, amino acids, liposomes, porphyrins, and serum albumin conjugates, etc., have been developed and studied as they could be more effective in BNCT. But still, the most commonly used boron compound is BPA, and it is the only compound that has been approved by the pharmaceutical authorities in Japan [10,11].…”

“…BNCT using a nuclear reactor has demonstrated its applicability in several clinical trials against highgrade gliomas [4][5][6][7][8][9]. And also BNCT using an accelerator-based neutron generator has been shown to be effective in treating high-grade gliomas [10]. BNCT using an accelerator-based neutron generator will soon become widely available in clinical settings because accelerator-based BNCT systems of can easily be set up in any hospital [10,11].…”

“…The most commonly used boron compound is boronophenylalanine (BPA), and it is the only compound that has been approved by the pharmaceutical authorities in Japan [10,11]. However, since some clinical cases in which BNCT using BPA are not very effective to such as deep-seated tumors or multiple lesions that require long irradiation times or multi-directional irradiation or BPA-resistant tumor cells exsit, further development of novel boron compounds is a key area of interest for improving the effectiveness of BNCT.…”

The Measurement of the Neutron Yield of the 7Li(p,n)7Be Reaction in Lithium Targets

“…As a result of neutron absorption by boron, a nuclear reaction 10 B(n,α) 7 Li occurs with high energy release in the cell, which leads to its destruction. In 2020, the BNCT technique, proposed in 1936, entered into clinical practice: two Japanese clinics began treating patients after successful clinical trials [ 2 , 3 ]. At present, four more BNCT clinics have been built in the world, including one in China, which is equipped with an accelerator-based neutron source developed at the Budker Institute of Nuclear Physics and commercialized by TAE Life Sciences (Santa Monica, CA, USA).…”

Tissue Architecture Influences the Biological Effectiveness of Boron Neutron Capture Therapy in In Vitro/In Silico Three-Dimensional Self-Assembly Cell Models of Pancreatic Cancers

“…Recently, with the development of neutron sources and boron agents, BNCT is becoming one of the most promising radiotherapies for aggressive cancers. For instance, a significant increase of survival rate of patients with glioblastoma was reported using accelerator-based BNCT [10]. Although the promising efficacy of BNCT for recurrent malignant gliomas and head and neck cancers has been reported in clinical studies [11], the potency of BNCT for pancreatic cancer treatment has not been fully explored.…”