Standardization and well planned clinical trials will still be necessary to establish Boron Neutron Capture Therapy (BNCT), a non-invasive therapeutic technique, for treating invasive malignant tumours, as a routine therapy option, but recent advances in the technology suggest that it may become a more common treatment option in coming years. These were among the main conclusions of an IAEA virtual meeting held last month.
A game changer for BNCT in recent years was the development of compact accelerator-based neutron sources (CANS) that are now being placed in hospitals, an environment much more suited to clinical applications than a research reactor, which is where patients previously had to undergo BNCT treatment.
“Most research reactors are not well equipped to handle patients, and there were only a few reactors where patients could undergo BNCT,” said Ian Swainson, Nuclear Physicist at the IAEA.
Although CANS offer new opportunities for clinical BNCT, they also provide a bit of a roadblock, as researchers and regulators need a better understanding of the differences between research reactors and accelerators regarding various treatment parameters, such as the different energies of neutrons that could vary according to the accelerated particle and neutron producing target. “CANS have not been in service long enough for experts to gather enough data,” said Swainson. “There are differences between research reactors and accelerators in the neutron fluxes produced and their energy distributions.” An upcoming IAEA report, whose development was the focus of the meeting, will act as a guidebook for the development of BNCT based at CANS in preclinical and later in clinical settings.
BNCT is a hybrid treatment, using both an external radiation source and a boron-containing pharmaceutical that needs to accumulate in the tumour to be effective. The CANS and pharmaceuticals require approvals from regulatory bodies both as radiation therapy and as a medicine, an additional complexity when compared to standard radiotherapy. An additional challenge will arise in comparing the patient’s results from one system to those from another. For this, standardized terminology and measurements as well as well-developed quality assurance programmes will be key.
Despite these complexities, a milestone towards establishing BNCT as a routine clinical cancer therapy came in March 2020 in Japan, when a manufacturer obtained approval of its accelerator as a medical device for BNCT, as part of a system along with the dose calculation programme and treatment planning system. A pharmaceutical containing boron, developed in parallel for that purpose by another company, has also received approvals. Both approvals followed the results from a Phase III clinical trial on advanced and recurrent head and neck cancer. In a crucial next step, the Japanese National Health Insurance approved reimbursements for BNCT treatment for this type of cancer in June 2020.
“These approvals are quite significant: BNCT has finally received official recognition as a therapeutic approach. In addition, a BNCT facility at the Helsinki University Hospital is approaching the end of its commissioning stage and will soon be seeking approvals from the regulatory authorities,” said Swainson. “Carefully designed clinical trials will be required to establish the efficacy of BNCT treatment versus existing treatment modalities for other cancers.”
Among areas still requiring development are standard methods for measuring boron concentration, particularly in the tumour during treatment. This is one of the complexities in reporting dose received by the patient from such procedures.
“There has been much encouraging data regarding BNCT treatment; however, there is a lack of clinically controlled, randomized trials, as the opportunity to conduct these trials in hospitals has been available for only a short time,” said Oleg Belyakov, Radiation Biologist at the IAEA. “In addition, there is a lack of standardization in how dose is reported, due to its complexity.”
More than 100 participants from 20 countries discussed new developments and scientific methodologies in BNCT at the meeting, the main conclusions of which will be summarized in an IAEA report expected to be published next year. The last IAEA publication on this topic was published in 2001 and is available here.
Read more about BNCT here.
