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. 2021 May 20;3(1):vdab067.
doi: 10.1093/noajnl/vdab067. eCollection 2021 Jan-Dec.

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

Shinji Kawabata  1 , Minoru Suzuki  2 , Katsumi Hirose  3 , Hiroki Tanaka  2 , Takahiro Kato  3 , Hiromi Goto  4 , Yoshitaka Narita  5 , Shin-Ichi Miyatake  1
Affiliations

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

Shinji Kawabata et al. Neurooncol Adv. .

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.

Keywords: accelerator; boron neutron capture therapy; clinical trial; glioblastoma.

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Figures

Figure 1.
Figure 1.
Overall survival in patients with glioblastoma.
Figure 2.
Figure 2.
Progression-free survival was evaluated by the RANO criteria in patients with glioblastoma.
Figure 3.
Figure 3.
Illustrated time series of all patients, including 24 with recurrent glioblastoma and 3 with recurrent malignant glioma (WHO grade III). Illustration showing the timing of progressive disease (PD) by the radiographical assessment/initiation of posttreatment as well as the changes in Karnofsky Performance Status (KPS) over time in each patient after BNCT. The symbols are illustrated in the figure caption.
Figure 4.
Figure 4.
Representative case of this trial. A 63-year-old female patient underwent surgery for a left temporal tumor with GB histology. She was followed up with a standard of care comprising fractionated XRT and TMZ. Unfortunately, 14 months after craniotomy, recurrence was recognized on follow-up MRI. She then entered into this clinical trial and received BNCT. BNCT could control the mass 1 year after treatment, although brain swelling occurred subsequently because of radiation injury. After PD assessment, she was administered BEV periodically. Edema was well-controlled, and no re-aggravation was observed. The patient continues to do well, with stabilized neurological status in the 3 years following BNCT. Some MR images in this figure were obtained outside the scope of this clinical trial; informed consent was obtained for use in this report from the patient.
See this image and copyright information in PMC

References

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