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Boron Neutron Capture Therapy — A Cancer Therapy

Outline

Neutron capture therapy (NCT) is a new type of radiation therapy. Currently, compounds containing boron are used for this therapy, and therefore the technique is commonly referred to as boron neutron capture therapy (BNCT).
One of the latest clinical radiation therapies currently in use is particle radiation therapy; the various types of this therapy can selectively irradiate cancer cells while causing little strain on the patient’s body, just as with NCT. However, the similarity of the two therapies ends there. In particle radiation therapy, beams of energetic particles directly attack cancer cells. In contrast, NCT uses beams of neutrons with hardly any energy; the radiation used to kill cancer cells is generated by nuclear reactions in or near the cancer cells.
NCT is a two-step procedure. The patient is first injected with a compound that only accumulates in or near cancer cells, and then is exposed to neutron beams. The cancer-localizing compound and neutrons undergo a nuclear reaction that emits particle radiation. It is this particle radiation that kills the cancer cells. As such, in NCT, neutron beams that have minimal impact on the human body selectively destroy cancer cells without harming normal cells. NCT is therefore garnering attention as a therapy that has no side effects and can significantly reduce strain on the patient. It is expected to be able to treat diseases that cannot be treated by current conventional radiation therapy techniques, such as malignant brain tumors and melanoma, as well as recurrent breast cancer, hepatic tumors, metastatic lung tumors, recurrent tumors, and polyoncosis.

NCT research was initiated in the United States, but many issues, relating to biology and applied physics, remained unresolved, such as the procedure’s strong, harmful effects on the brain, and efforts to introduce NCT on a wide scale via medical institutions ended in failure. In Japan, NCT research began in 1959. One of the first breakthroughs came in 1968, when Hiroshi Hatanaka, a dedicated researcher in the field and an assistant at the Department of Neurosurgery of the University of Tokyo at the time, conducted Japan’s first medical irradiation in conjunction with Hitachi Ltd; the results surpassed those of clinical trials conducted in the United States. Since then, compounds containing boron have been developed to be injected into patients, and there are now 13 clinical examples of BNCT being used to treat malignant brain tumors. Today, NCT research has advanced even further in Japan. A body of evidence has now been gathered indicating the therapeutic efficacy of NCT; there are now over 200 case reports of the treatment of brain tumors with NCT, and 30 reports of the treatment of malignant melanoma. Encouraged by the success in Japan, the United States resumed NCT research in the 1990s, and many other countries, including several European Union member states, Russia, and Taiwan have also initiated NCT research.

NCT research in Japan now encompasses the development of medical devices for practical use. Formerly, NCT could not be performed in hospitals because the neutrons used to trigger the nuclear reactions with cancer cells could only be produced using a nuclear reactor. More recently, however, it has become possible to produce neutrons without the use of nuclear reactors, through the development of compact accelerators, through programs of collaboration between industry and universities, involving such parties as Kyoto University, the University of Tsukuba, Sumitomo Heavy Industries (SHI), and Mitsubishi Heavy Industries.
At the Kyoto University Research Reactor Institute, Koji Ono, a Kyoto University Professor Emeritus who has been conducting NCT research for over 20 years, has collaborated with SHI and Stella Chemifa, a chemicals company, to develop an accelerator-based neutron irradiation system. Clinical trials for this system officially started in September 2012. The system is the first in the world intended to be used for NCT administered in actual clinical settings.
In this system, operational procedures are simplified and the risk of radiation exposure averted through the miniaturization of neutron sources, leading to improved safety. Furthermore, compact accelerators eliminate the need to transport patients from the hospital to a nuclear reactor, making NCT more convenient. Compact accelerators for NCT may also reduce the costs incurred by hospitals in the administration of treatment. Estimated figures suggest that while treatments that use devices to generate heavy particle beams or proton beams incur a cost of about 3 million yen per treatment, NCT can reduce that figure to about 1.5 million yen. The development of compact accelerators, therefore, must be seen as a big step towards the actual clinical use of NCT.

The National Cancer Center of Japan has been collaborating with a private company, Cancer Intelligence Care Systems Inc., in order to conduct the world’s first clinical BNCT research. The BNCT research facilities were built within the hospital and the system implemented in 2014. After performance tests, the system passed the facility inspection by the Nuclear Safety Technology Center in November 2015. The next step will be at the earliest in 2016, when clinical trials begin.
Another BNCT system developed by Kyoto University in collaboration with SHI and Stella Chemifa was installed and implemented at Southern Tōhōku General Hospital in Koriyama City, Fukushima Prefecture. Clinical trials on the treatment of head and neck cancer began in January 2016. The goal of the trials is to obtain the approval of the Japanese Ministry of Health, Labour and Welfare by 2018 to use BNCT as an advanced medical technology.
In April 2013, SHI, in collaboration with the Japanese government, announced a proposal to export medical services and facilities to Russia. The proposal includes building a hospital in Moscow equipped with SHI’s radiation therapy system and to provide facilities and human resources from Japan. In 2015, an agreement including a scheme of the project and implementation schedule was arranged and the MOU was concluded between Japanese and Russian representative bodies. As the project proceeds, the first BNCT clinical experiments will be conducted outside of Japan. Should the practical application of BNCT in clinical settings in Russia become a reality, the possibility of exporting BNCT systems to countries in Europe and North America may be considered, providing an opportunity to introduce Japan’s medical technologies to the world.



Revised on 30 March 2016 regarding the implementation of each institution.

Originally written on 27 August 2013.

About the authors:

Azusa Kotaka and Hiromi Jitsukata are reporters for Japanest NIPPON.

http://www.rri.kyoto-u.ac.jp/en
( Kyoto University Research Reactor Institute )
http://www.shi.co.jp/english/info/2012/6kgpsq0000001jc0.html
( Sumitomo Heavy Industries, Ltd. March 11, 2013 )
Cyclotron (accelerator) jointly developed by Kyoto University and SHI
Specifications
Type AVF cyclotron with external ion source
Accelerating particle H
Extracted particle H
Extraction energy 30 MeV
Beam current 1 mA
Ion source Multi-cusp type

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