Clinical research in neutron capture therapy

Abstract

A 1.5-day workshop to assess the current state of the science in neutron capture therapy (NCT) was convened at the request of the Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute and the U.S. Department of Energy. The topics were primarily clinical with physics, chemistry, and biology relevant to the immediate trials discussed. The morning of the first day was directed toward updates on epithermal neutron sources, the chemistry of medicinal boron compounds, and preclinical studies. In the afternoon, participants from Europe, Asia, and North America were invited to present their clinical experience with NCT. The participants then separated into breakout sessions. The following morning session included presentations and discussions of each breakout session. These are presented below. NCT was first proposed in 1936, just 4 years after the neutron itself was discovered. NCT is a unique form of radiotherapy that carries a potential for a significant improvement in therapeutic gain. The classification of neutrons into energy categories is somewhat arbitrary, but for the present purpose “thermal neutrons” have an energy 1 eV, “epithermal neutrons” have an energy between 1 eV and 10 KeV, and “fast neutrons” may be considered, for therapeutic purposes, to be in the megavoltage range. NCT is a form of binary therapy, similar to photodynamic therapy, in which neither the thermal neutrons nor the boron carrier molecule has significant cytotoxic effect but produces highly radiobiologically effective particles when the two interact. This is in contrast to the more familiar “fast neutrons,” which are highly radiobiologically effective by themselves. These reactions between a neutron carrier molecule such as boron-10 (B-10) and thermal neutrons produce He-4 and Li-7 ions of very high linear energy transfer (LET) but very short ( 10 m) range. This therapy was first studied in glioblastoma in 1951 using crude thermal neutron beams and B-10–enriched boric acid. Since then, NCT has been studied in several countries, usually with glioblastoma. The difficulties with NCT were, and continue to be, difficulty in finding appropriate neutron beams, a scarcity of suitable boron carrier agents, uncertain dosimetry, and a lack of rigorous and reproducible clinical trials. This workshop was convened to address these issues. These issues were divided into three broad topics: carrier agent development, preclinical studies, and clinical studies.