Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

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Abstract

The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.

Highlights

► In this study, we evaluate the clinical outcome of boron neutron capture therapy (BNCT) for malignant brain tumors. ► We have treated 23 glioblastoma (GBM) patients with BNCT without any additional chemotherapy. ► Clinical results of BNCT in patients with GBM are superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.

Introduction

In 1968, Hatanaka introduced sodium borocaptate (BSH) as a boron carrier in Japan, and in 1968–1998, more than 170 patients with malignant intacranial tumors, especially GBM, were treated with BNCT, combined with BSH and pure thermal neutron beam. The clinical outcomes were favorable in patients whose GBMs were located within a 4 cm depth from the brain surface. However, they were unsatisfactory in patients whose tumors were situated in deeper regions, because neutron fluence delivery into the deep regions was inadequate (Hatanaka and Nakagawa, 1994, Nakagawa and Hatanaka, 1997, Nakagawa et al., 2003). Therefore, the epithermal neutron beam was developed to improve neutron delivery. The use of epithermal neutron beam can improve thermal neutron distribution in deeper sites, which, in turn, will increase the therapeutic efficacy of BNCT. We have started BSH-based intra-operative BNCT in 1998 using epithermal neutron beam and gold wire measurement as a BNCT dose planning. Recently, boronophenylalanine (BPA) as a new boron compound was introduced in treatment of GBM using BNCT. It is widely accepted that BPA is actively taken up by tumor cells. Moreover, computational dosimetry system (JCDS) was developed. The introduction of epithermal neutron beam, clinical use of BPA and new dose planning system of BNCT could make possible of clinical apply of non-operative BNCT(NO-BNCT) using the combination of BSH and BPA. We have shifted from IO-BNCT to NO-BNCT in 2005. In this study, we analyzed BNCT radiation dose and clinical outcome between IO- and NO-BNCT.

Section snippets

Material and methods

We have treated 23 GBM patients with BNCT, including 17 patients with IO-BNCT, and 6 patients with NO-BNCT. IO-BNCT was carried out using 100 mg/kg BSH through intravenous infusion within one hour 12–15 h before neutron irradiation. On the day of BNCT, craniotomy was done under general anesthesia to irradiate neutron beam directly to tumor tissue. Neutron flux was measured using gold wires, which were inserted around tumor cavity. NO-BNCT was carried out using the combination of 100 mg/kg BSH and

Results

  • GTV dose (Table 2)

    The minimal physical and weighted dose of GTV in IO-BNCT were 18.3±5.3 Gy and 52.1±14.2 Gy(w), respectively. These in NO-BNCT were 7.8±2.5 Gy and 27.7±8.7 Gy(w), respectively. The NO-BNCT to IO-BNCT ratio were 0.43 in physical dose and 0.53 in weighted dose.

  • CTV dose (Table 3)

    The minimal physical and weighted dose of CTV in IO-BNCT were 11.8±5.6 Gy and 35.8±4.6 Gy(w), respectively. These in NO-BNCT were 4.2±1.1 Gy and 15.2±4.3 Gy(w), respectively. The NO-BNCT to IO-BNCT ratio were 0.36

Discussion

In previous BNCT study, radiation dose was evaluated with gold wire measurement. During neutron irradiation in IO-BNCT, several gold wires were inserted into and/or around the tumor tissue to measure neutron flux. The development of computer-based dose planning system for BNCT, which is called as a JCDS, can make possible the comparison of the radiation doses between IO- and NO-BNCT. We have reported the radiation dose of IO-BNCT using gold wire measurement (Kageji et al., 2006). In this study,

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