Boron neutron capture therapy combined with early successive bevacizumab treatments for recurrent malignant gliomas – A pilot study

Hiroyuki Shiba, Koji Takeuchi, Ryo Hiramatsu, Motomasa Furuse, Naosuke Nonoguchi, Shinji Kawabata, Toshihiko Kuroiwa, Natsuko Kondo, Yoshinori Sakurai, Minoru Suzuki, Koji Ono, Shiro Oue, Eiichi Ishikawa, Hiroyuki Michiue, Shin Ichi Miyatake

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Recurrent malignant gliomas (RMGs) are difficult to control, and no standard protocol has been established for their treatment. At our institute, we have often treated RMGs by tumor-selective particle radiation called boron neutron capture therapy (BNCT). However, despite the cell-selectivity of BNCT, brain radiation necrosis (BRN) may develop and cause severe neurological complications and sometimes death. This is partly due to the full-dose X-ray treatments usually given earlier in the treatment course. To overcome BRN following BNCT, recent studies have used bevacizumab (BV). We herein used extended BV treatment beginning just after BNCT to confer protection against or ameliorate BRN, and evaluated; the feasibility, efficacy, and BRN control of this combination treatment. Seven patients with RMGs (grade 3 and 4 cases) were treated with BNCT between June 2013 and May 2014, followed by successive BV treatments. They were followed-up to December 2017. Median overall survival (OS) and progression-free survival (PFS) after combination treatment were 15.1 and 5.4 months, respectively. In one case, uncontrollable brain edema occurred and ultimately led to death after BV was interrupted due to meningitis. In two other cases, symptomatic aggravation of BRN occurred after interruption of BV treatment. No BRN was observed during the observation period in the other cases. Common terminology criteria for adverse events grade 2 and 3 proteinuria occurred in two cases and necessitated the interruption of BV treatments. Boron neutron capture therapy followed by BV treatments well-prevented or well-controlled BRN with prolonged OS and acceptable incidence of adverse events in our patients with RMG.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
Journalneurologia medico-chirurgica
Issue number12
Publication statusPublished - 2018


  • Bevacizumab
  • Boron neutron capture therapy
  • Brain radiation necrosis
  • Recurrent malignant glioma

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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