Clinical results of sodium borocaptate (BSH)-based intraoperative boron neutron capture therapy (IO-BNCT)

Abstract

The first clinical trials of BNCT were conducted at the Brookhaven Graphic Reactor and the Brookhaven Medical Research Reactor during 1951 and 1952 and at the Massachusetts Institute of Technology Reactor from 1959 to 1962 [3]. The boron compounds used were boric acid and borate as the boron carrier. The clinical results were discouraging: none of the patients survived for 1 year. Serious complications such as acute brain swelling and delayed cerebral necrosis resulted from the high boron content in the blood and normal brain tissue [3]. In 1968, Hatanaka introduced BSH as a boron carrier in Japan, and between 1968 and 1998 more than 170 patients with malignant intracranial tumors, especially GBM, were treated with BNCT in combination with BSH and pure thermal neutron beam [4, 5, 12, 13]. For BNCT to become a useful treatment modality, it is crucial that boron compounds be evaluated biologically and clinically. The clinical outcomes were favorable in patients whose GBM were located within a 4-cm depth from the brain surface [4, 5]. However, they were unsatisfactory in patients whose tumors were situated in deeper regions because neutron fluence delivery into deep regions was inadequate. Therefore, the epithermal neutron beam was developed at several international institutions to improve neutron delivery. At the Japan Atomic Energy Research Institute (JAERI) and the Kyoto University Research Reactor Institute (KUR) in Japan, mixed epithermal and thermal neutron beams were introduced for BNCT in 1998, before the independent introduction of epithermal neutron beam. Use of the mixed neutron beam can improve thermal neutron distribution in deeper sites, which in turn increases the therapeutic efficacy of BNCT. We have performed BSH-based intraoperative BNCT using mixed epithermal and thermal neutron beams since 1998. During neutron irradiation, inserted gold wires are used to measure neutron flux around and into the tumor tissue. Using neutron flux data obtained from individual points such as the brain surface, the center of the tumor bulk, and the area of invasion, we can analyze the actual radiation dose at each point. With these accurate radiation-dose data, we can then study the clinical course of each BNCT-treated patient.