External beam BNCT for glioblastoma multiforme

Abstract

Despite the recent improvements in multimodal therapies that include surgery, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) easily recurs and continues to have a median overall survival time of less than 1.5 year. Eight nonrandomized prospective external beam BNCT trials have been performed over 15 years. The p-dihydroxyboryl-phenylalanine (BPA)-mediated BNCT was performed in the Brookhaven National Laboratory (BNL) trial, the trial of Harvard/MIT, the trial of University of Helsinki and VTT (Technical Research Centre of Finland), and the trial of Studsvik. The sulfhydryl borane Na2B12H11SH (BSH)-mediated BNCT was performed in the European Organisation for Research and Treatment of Cancer (EORTC) 11961 trial and the trial of Nuclear Research Institute (NRI) in Rez. The combination of BPA and BSH was used in the trial of Osaka Medical College and the trial of University of Tsukuba and JAEA. In the trial of Studsvik and Osaka Medical College, the long-term infusion of BPA was employed. Additional photon irradiation was performed in the trial of Osaka Medical College and the trial of University of Tsukuba and Japan Atomic Energy Agency (JAEA). Four of eight studies, even in subgroups of the patient population, suggest that external beam BNCT may improve survival in newly diagnosed GBM. Of these eight studies, four primarily phase I trials demonstrated only modest toxicity. The median time to progression and the median survival time vary from 6 to 12 months and 12 to 27 months, respectively.