Abstract
In April 2022, the National Cancer Institute of the United States organized a 3-day seminar, dedicated to boron neutron capture therapy (BNCT). This short article summarizes a presentation from that event, which is intended to provide an overview of activities currently underway worldwide to make BNCT available for patient treatments. This overview does not claim to be exhaustive but shows a great deal of activity in all areas necessary for the complex therapy that is BNCT. A rapid increase in the number of BNCT centers can be expected over the next few years, coupled with the introduction of novel drugs for BNCT. It will be a major challenge to all stakeholders to create clinical networks that can conduct the necessary prospective clinical trials in a short time and in high quality.
Introduction
Boron neutron capture therapy (BNCT) is based on the ability of the nonradioactive isotope boron-10 to interact with a very high probability with thermal neutrons resulting in two charged particles namely helium and lithium nuclei. Both particles have a high linear energy transfer and, therefore, a very high biological effectiveness. Their range in tissue is very short (∼10 μm), which corresponds approximately to the diameter of one mammalian cell. 1 If these reactions can be selectively triggered in tumor cells, some kind of “cell-surgery” will be reached to destroy individual tumor cells that invade normal tissue without damaging the surrounding healthy structures—a highly effective weapon in the fight against cancer.
Until recently, the high-intensity low-energy neutron fields were only available at nuclear research reactors. Such infrastructure is usually located far from the treating hospital and is generally only available for patient care for limited periods of time. It was hardly possible to treat sufficiently large cohorts of patients to obtain statistically meaningful data on the success of this therapy. The lack of neutron sources for BNCT in hospitals has hindered the development of this modality. Recently, this problem could be solved by advances in accelerator technologies.
Accelerators and beam delivery systems based on different technical solutions are now commercially available for BNCT at prices below the costs for a proton facility and, therefore, achievable for large hospitals interested in advanced cancer treatment modalities. Owing to the expected four times higher patient throughput per treatment room and competitive business model, combining BNCT system and drug, BNCT is becoming attractive for investors. In this article, the description of the current situation of accelerator-based BNCT efforts is attempted. The information has been compiled to the best of the authors' knowledge and belief but make no claim to completeness.
BNCT Industries
For >7 decades, BNCT has been dependent on government-controlled nuclear research facilities, and preclinical and clinical research has been conducted under purely academic aspects without the involvement of the pharmaceutical industry or medical device manufacturers. This is about to change thoroughly. Hereunder are lists of current efforts known to develop and market BNCT systems and drugs on a commercial basis. Efforts in research institutions pursuing this goal are also included. Manufacturers who intend to bring neutron sources for BNCT to the market are summarized in Table 1.
Accelerator-Based Boron Neutron Capture Therapy Systems
BNCT, boron neutron capture therapy; CAS, Chinese Academy of Science; CICS, Cancer Intelligence Care Systems; FDS, frontier development of science; IHEP, Institute of High Energy Physics; NTS, neuboron therapy system; SiC, silicon carbide; TAE, Tri Alpha Energy.
Table 4 also includes systems that are being developed, at least initially, as prototypes by or for individual therapy centers. A later commercialization is not excluded. In this presentation, the details of the different target systems are not gone into. Currently, targets made of beryllium or lithium are used. The trend seems to go in the direction of lithium-based targets (see also Table 1). Table 2 lists pharmaceutical companies that, to authors' knowledge, sell raw substances or drugs for BNCT or work on their production.
Boron Neutron Capture Therapy Pharmaceutical Industries
API, active pharmaceutical ingredient; BPA, borono-phenylalanine; BSH, sodium borocaptate; SAS, Société par actions simplifiée.
This does not include the many university research efforts. An overview of potential candidates for future drugs is provided by the following website (
Other Industries Related to Clinical Boron Neutron Capture Therapy
Boron Neutron Capture Therapy Treatment Centers (Accelerator Based)
Bold text relates to facilities in operation or in the process of being commissioned.
CIAE, China Institute of Atomic Energy; CNAO, Centro Nazionale di Adroterapia Oncologica; CNEA, Comision Nacional Energia Atomica; HI, Heavy Industries; IBA, Ion Beam Applications; KIRAMS, Korea Institute of Radiological and Medical Sciences; LS, Life Sciences.
Conclusions
Up to now, radiation therapy (RT) is one of the most powerful tools to treat any kind of cancer.
RT is a growing market with a volume of approximately USD 6.1 billion in 2022. Global cancer burden is on the rise—24.6 million new cancer cases per year are expected by 2030. 2 Conventional RT using photons and electrons as well as brachytherapy is well established. Every year, there are major innovations for conventional RT that bring improvements, especially in terms of precision. However, despite the best efforts, the authors continue to observe unsatisfactory clinical outcomes in some challenging indications. BNCT has the potential to successfully treat these currently incurable cancers.
Currently the best example is recurrent head and neck cancer. 3,4 This expectation, together with the new technologies already mentioned, could explain the tremendous activity in the field of BNCT that is being currently witnessed.
Medical
Interest in BNCT in the medical community has increased rapidly. BNCT centers are being established worldwide. Results of well-designed controlled clinical trials will soon be available. In Japan, one indication, namely BNCT for recurrent head and neck tumors after maximal therapy with surgery, high dose radiation/chemotherapy is already reimbursed by the national health care system.
Industry
Several vendors for hospital-based BNCT systems are on the market, and more will follow. An important aspect is the increasing interest from the pharmaceutical industry to participate in this nascent market. It can also be seen that developments that BNCT needs for its further progress are taken up by dedicated industries, be it the development of software for irradiation equipment, for irradiation planning, neutron dosimetry or a professional setup, and support of therapy centers.
Sciences and politics
There is growing interest in BNCT from scientific journals and scientific societies, especially in radiation oncology. A growing support especially also from the National Cancer Institute of the United States, combined with a somewhat more positive evaluation of BNCT when applying for research funding can also be observed. International Atomic Energy Agency is preparing a new version of the TECDOC on BNCT first published in 2001. 5 Several national and international scientific societies are dedicated to the topic of BNCT or have established a BNCT subcommittee (Table 5).
Scientific Societies Focusing on Boron Neutron Capture Therapy
In summary, a paradigm shift has occurred, largely resulting from the recent availability of hospital-based neutron sources for BNCT. Success will now depend on well-designed clinical trials producing reproducible results, which can only be achieved through close co-operation between the different BNCT centers. This will be a major challenge in the coming years. The step from experimental approaches to a therapy modality that has reached clinical routine requires close cooperation with the regulatory authorities. So far, only the Japanese Pharmaceuticals and Medical Devices Agency has first experience with approvals of medical devices and drugs for BNCT.
However, the focus has been on the neutron source, and the development of truly innovative drugs has not yet progressed as far. In these discussions, care should be taken to ensure that approvals for drugs are not linked to a specific irradiation device, as this would significantly jeopardize further development of BNCT.
Footnotes
Authors' Contributions
W.A.G.S. designed the concept, W.A.G.S. and M.U. collected data, W.A.G.S. wrote the article, and M.U. proofread the article
Disclosure Statement
W.A.G.S. is Founder and President of the commercial company “BNCT Global GmbH.” M.U. has no financial disclosures.
Funding Information
No funding was received for this article.