Properties of paraffin wax as a bolus material in accelerator-based boron neutron capture therapy

The aim of this study is the development of an irradiation method for the treatment of superficial tumours using a hydrogel bolus to produce thermal neutrons in accelerator-based Boron Neutron Capture Therapy (BNCT).To evaluate the neutron moderating ability of a hydrogel bolus, a water phantom with a hydrogel bolus was irradiated with an epithermal neutron beam from a cyclotron-based epithermal neutron source. Phantom simulating irradiation to the plantar position was manufactured using three-dimensional printing technology to perform an irradiation test of a hydrogel bolus. Thermal neutron fluxes on the surface of a phantom were evaluated and the results were compared with the Monte Carlo-based Simulation Environment for Radiotherapy Applications (SERA) treatment planning software. It was confirmed that a hydrogel bolus had the same neutron moderating ability as water, and the calculation results from SERA aligned with the measured values within approximately 5%. Furthermore, it was confirmed that the thermal neutron flux decreased at the edge of the irradiation field. It was possible to uniformly irradiate thermal neutrons by increasing the bolus thickness at the edge of the irradiation field, thereby successfully determining uniform dose distribution. An irradiation method for superficial tumours using a hydrogel bolus in the accelerator-based BNCT was established.

Boron Neutron Capture Therapy (BNCT) research in the United States has focused on the use of epithermal (0.5 eV to 10 key) neutron beams for treatment of certain highly-malignant primary brain tumors and possibly for treatment of metastatic malignant melanoma. Various types of epithermal neutron sources for BNCT have been proposed over the years. Reactor-based sources, accelerator-based sources, and radioactive neutron sources have all been extensively examined. The first practical, large-scale, epithermal neutron beam for BNCT was installed at the Brookhaven Medical Research Reactor (BMRR)1. This beam was designed and constructed in a cooperative effort between Brookhaven National Laboratory (BNL) and the Idaho National Engineering Laboratory (INEL). It has been used extensively for BNCT research activities conducted by INEL, BNL, and others.

<p indent=0mm>Boron neutron capture therapy (BNCT) is regarded as a revolutionary means for high-accuracy cancer therapy with cell level selectivity. It has unique therapeutic effects for some malignance, such as glioblastoma multiforme, melanoma, recurrent head and neck malignance. It can also be used for cancer treatment of deep organ, such as liver and lung. Even though its principle was proposed about <sc>80 years</sc> ago, it has never been utilized in routine clinic therapy in hospital until 2020. BNCT, as a binary therapeutic method, greatly depends on both high-quality neutron beam and highly target-selective boron drug. Tumor killing in cell-level accuracy can be achieved only when the two elements work together and collaborate closely. To realize such therapeutic effect, BNCT sets high requirement on both neutron source and boron drug. The research on boron drug is related with multi-disciplines, such as chemistry, biology, medicine, radiology, pharmacy and physics. This article focuses on the neutron source for BNCT. Commonly, there are two types of BNCT neutron sources: reactor-based neutron source and accelerator-based neutron source. Up to now, almost all clinic trails of BNCT therapy were performed with the former. Due to limited resources of reactor neutron source, only less than 2000 cases BNCT treatments have been carried out in the world since BNCT method was invented. Thanks for the intense beam proton accelerator development, accelerator based neutron source can provide better beam quality, and especially importantly it can be installed in a hospital environment, which is essential for wide-range application of BNCT. In accelerator-based BNCT field, China has a sound base owing to more than <sc>20 years</sc> research and development in high intensity neutron source for spallation neutron source and accelerator-driven subcritical system. It is meaningful work to transfer the related technology to accelerator-based BNCT (AB-BNCT). In this paper we will firstly introduce the demand on neutron beam specification recommended by IAEA. Then the difficulties in BNCT slow development in passing decades are reviewed. New era of BNCT is coming and one can expect a prosperous future, owing to accelerator-based BNCT. The core technology of AB-BNCT is explored and recent research achievements on BNCT research and development in China are reported. Various types of accelerators now can be used for BNCT facility, including electro-static high voltage, cyclotron and RF linac. Their pro and con are reviewed. Majorly two kinds of neutron generation targets are utilized for BNCT, and the characteristics comparison of these two are analyzed. On the newly constructed BNCT research platform in China, new boron drug research and development work are conducted in many institutes, universities and pharmacy companies. And in recent, a new AB-BNCT facility is under construction for clinic trails in a hospital. So we can have an optimistic viewpoint for BNCT future in China.

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator‐based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton‐induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose‐volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator‐based BNCT treatment.

CURRENT RESEARCH ON ACCELERATOR-BASED BORON NEUTRON CAPTURE THERAPY IN KOREA

This study aimed to identify the required capabilities and workload of medical staff in accelerator-based boron neutron capture therapy (BNCT). From August to September 2022, a questionnaire related to the capabilities and workload in the accelerator-based BNCT was administered to 12 physicians, 7 medical physicists and 7 radiological technologists engaged in BNCT and 6 other medical physicists who were not engaged in BNCT to compare the results acquired by those engaged in BNCT. Only 6–21% of patients referred for BNCT received it. Furthermore, 30–75% of patients who received BNCT were treated at facilities located within their local district. The median required workload per treatment was 55 h. Considering additional workloads for ineligible patients, the required workload reached ~1.2 times longer than those for only eligible patients’ treatment. With respect to capabilities, discrepancies were observed in treatment planning, quality assurance and quality control, and commissioning between medical physicists and radiological technologists. Furthermore, the specialized skills required by medical physicists are impossible to acquire from the experience of conventional radiotherapies as physicians engaged in BNCT were specialized not only in radiation oncology, but also in other fields. This study indicated the required workload and staff capabilities for conducting accelerator-based BNCT considering actual clinical conditions. The workload required for BNCT depends on the occupation. It is necessary to establish an educational program and certification system for the skills required to safely and effectively provide BNCT to patients.

Boron neutron capture therapy (BNCT) has a unique property of tumor-cell-selective heavy-particle irradiation. BNCT can form large dose gradients between cancer cells and normal cells, even if the two types of cells are mingled at the tumor margin. This property makes it possible for BNCT to be used for pre-irradiated locally recurrent tumors. Shallow-seated, locally recurrent lesions have been treated with BNCT because of the poor penetration of neutrons in the human body. BNCT has been used in clinical studies for recurrent malignant gliomas and head and neck cancers using neutron beams derived from research reactors, although further investigation is warranted because of the small number of patients. In the latter part of this review, the development of accelerator-based neutron sources is described. BNCT for common cancers will become available at medical institutes that are equipped with an accelerator-based BNCT system. Multiple metastatic lung tumors have been investigated as one of the new treatment candidates because BNCT can deliver curative doses of radiation to the tumors while sparing normal lung tissue. Further basic and clinical studies are needed to move toward an era of accelerator-based BNCT when more patients suffering from refractory cancers will be treated.

Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail. The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system. In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived. The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p=0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p=0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities. This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

Beam shaping assembly design of Li(p,n) neutron source with a rotating target for boron neutron capture therapy

Clinical studies of boron neutron capture therapy (BNCT) have been conducted using thermal and epithermal neutron beams generated from research reactors. Considering the spread and development of BNCT, it has been desired to realize BNCT using an accelerator-based neutron source that can be installed in medical institutions. To date, the accelerator-based BNCT has been developed by combining various accelerators such as a cyclotron and a linear accelerator with neutron generation targets. In Japan, the world's first treatment system using a combination of a cyclotron and a beryllium target has received manufacturing and marketing approval as a medical device. In June 2020, BNCT insurance medical treatment was started at medical institutions. Currently, BNCT is being performed for cases of locally unresectable recurrent or unresectable advanced head and neck cancer. In this paper, it is shown that the history of reactor-based BNCT and the current development status and future prospects of the accelerator-based BNCT, which has been carried out in advance in Japan.

Boron Neutron Capture Therapy (BNCT) is an advanced form of radiotherapy technique that is potentially superior to all conventional techniques for cancer treatment, as it is targeted at killing individual cancerous cells with minimal damage to surrounding healthy cells. After decades of development, BNCT has reached clinical-trial stages in several countries, mainly for treating challenging cancers such as malignant brain tumors. The Indonesian consortium of BNCT already developed of the design BNCT for many cases of type cancers using many neutron sources. The main objective of the Indonesian consortium BNCT are the development of BNCT technology package which consists of a non nuclear reactor neutron source based on cyclotron and compact neutron generator technique, advanced boron-carrying pharmaceutical, and user-friendly treatment platform with automatic operation and feedback system as well as commercialization of the BNCT though franchised network of BNCT clinics worldwide. The Indonesian consortium BNCT will offering to participate in Boron carrier pharmaceuticals development and testing, development of cyclotron and compact neutron generators and provision of neutrons from the 100 kW Kartini Research Reactor to guide and to validate compact neutron generator development. Studies were carried out to design a collimator which results in epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) at the Kartini Research Reactor by means of Monte Carlo N-Particle 5 (MCNP5) codes. Reactor within 100 kW of output thermal power was used as the neutron source. The design criteria were based on the IAEA’s recommendation. All materials used were varied in size, according to the value of mean free path for each. Monte Carlo simulations indicated that by using 5 cm thick of Ni as collimator wall, 60 cm thick of Al as moderator, 15 cm thick of 60Ni as filter, 1,5 cm thick of Bi as "-ray shielding, 3 cm thick of 6Li2CO3-polyethylene as beam delimiter, with 3-5 cm varied aperture size, epithermal neutron beam with minimum flux of 7,8 x 108 n.cm-2.s-1, maximum fast neutron and "-ray components of, respectively, 1,9 x 10-13 Gy.cm2.n-1 and 1,8 x 10-13 Gy.cm2.n-1, maximum thermal neutron per epithermal neutron ratio of 0,009, and beam minimum directionality of 0,72, could be produced. The beam did not fully pass the IAEA’s criteria, since the epithermal neutron flux was still below the recommended value, 1,0 x 109 n.cm-2.s-1. Nonetheless, it was still usable with epithermal neutron flux exceeded 5 x 108 n.cm-2.s-1. When this collimator was surrounded by 8 cm thick of graphite, the characteristics of the beam became better that it passed all IAEA’s criteria with epithermal neutron flux up to 1,7 x 109 n.cm-2.s-1. it is still feasible for BNCT in vivo experiment and study of many cases cancer type i.e.; liver and lung curcinoma. In this case, thermal neutron produced by model of Collimated Thermal Column Kartini Research Nuclear Reactor, Yogyakarta. Sodium boroncaptate (BSH) was used as in this research. BSH had effected in liver for radiation quality factor as 0.8 in health tissue and 2.5 in cancer tissue. Modelling organ and source used liver organ who contain of cancer tissue and research reactor. Variation of boron concentration was 20, 25, 30, 35, 40, 45, and 47 $g/g cancer. Output of MCNP calculation were neutron scattering dose, gamma ray dose and neutron flux from reactor. Given the advantages of low density owned by lungs, hence BNCT is a solid option that can be utilized to eradicate the cell cancer in lungs. Modelling organ and neutron source for lung carcinoma was used Compact Neutron Generator (CNG) by deuterium-tritium which was used is boronophenylalanine (BPA). The concentration of boron-10 compound was varied in the study; i.e. the variations were 20; 25; 30; 35; 40 and 45 μg.g-1 cancer tissues. Ideally, the primary dose which is solemnly expected to contribute in the therapy is alpha dose, but the secondary dose; i.e. neutron scattering dose, proton dose and gamma dose that are caused due to the interaction of thermal neutron with the spectra of tissue can not be simply omitted. Thus, the desired output of MCNPX; i.e. tally, were thermal and epithermal neutron flux, neutron and photon dose. The liver study variation of boron concentration result dose rate to every variation were0,042; 0,050; 0,058; 0,067; 0,074; 0,082; 0,085 Gy/sec. Irradiation time who need to every concentration were 1194,687 sec (19 min 54 sec);999,645 sec (16 min 39 sec); 858,746 sec (14 min 19 sec); 743,810 sec (12 min 24 sec); 675,156 sec (11 min 15 sec); 608,480 sec (10 min 8 sec); 585,807sec (9 min 45 sec). The lung carcinoma study variations of boron-10 concentration in tissue resulted in the dose rate of each variables respectively were 0.003145, 0.003657, 0.00359, 0.00385, 0.00438 and 0.00476 Gy.sec-1 . The irradiated time needed for therapy for each variables respectively were 375.34, 357.55, 287.58, 284.95, 237.84 and 219.84 minutes.

A design for a slab reactor to produce an epithermal neutron beam and a thermal neutron beam for use in neutron capture therapy (NCT) is described. A thin reactor with two large-area faces, a slab reactor, was planned using eighty-six 20% enriched TRIGA fuel elements (General Atomics), San Diego, California) and four B 4 C control rods. Two neutron beams were designed: an epithermal neutron beam from one face and a thermal neutron beam from the other. The planned facility, based on this slab-reactor core with a maximum operating powere of 300 kW, will provide an epithermal neutron beam of 1.8×10 9 n epi /cm 2 -s intensity with low contamination by fast neutrons (2.6×10 -13 Gy-cm 2 /n epi ) and gamma rays (<1.0×10 -13 Gy-cm 2 /n epi ) and a thermal neutron beam of 9.0 10 9 n th /cm 2 -s intensity with low fast-neutron dose (1.0 10 -13 Gy-cm 2 /n th ) and gamma dose (<1.0×10 -13 Gy-cm 2 /n th ). Both neutron beams will be forward directed. Each beam can be turned on and off independently through its individual shutter. A complete NCT treatment using the designed epithermal or thermal neutron beam would tale 30 or 20 min, respectively, under the condition of assuming 10 μg 10 B/g in the blood. Such exposure times should be sufficiently short to maintain near-optimal targert (e.g., 10 B, 157 Gd, and 235 U) distribution in tumor versus normal tissues throughout the irradiation. With a low operating power of 300 kW, the heat generated in the core can be removed by natural convection through a pool of light water. The proposed design in this study could be constructed for a dedicated clinical NCT facility that would operate very safely

Boron neutron capture therapy (BNCT) was conducted in a hospital using an accelerator-based neutron source. The neutron beam intensity at the patient position was evaluated offline using a gold-based neutron activation method. During BNCT neutron beam irradiation on patients, the neutron intensity was controlled in real time by measuring the proton beam current irradiated on a lithium neutron target. The neutron intensity at NCCH decreased owing to the degradation of the lithium neutron target during neutron irradiation. The reduction in the neutron beam intensity could not be monitored via proton beam measurement due to the dependence of neutron production on the neutron targetcondition. The duration of BNCT neutron irradiation should be controlled by monitoring the neutron beam intensity with a real-time neutron detector for reliable neutron irradiation on patients. The measurement accuracy of the online neutron beam monitor was experimentally obtained by comparing the gold radioactivity measured at the patient position. Radiation-induced damage was observed from the variation in the pulse height distributions of multichannel analyzer during long-term neutronexposure. Neutron beams were measured during neutron beam irradiation at the BNCT facility of Edogawa hospital in Japan using a neutron beam monitor comprising a 0.07- LiF layer and 40- back-illuminated thin Si pin diode. The proton beam was continuously irradiated until a cumulative total beam charge of approximately 3 kC was achieved. The online neutron beam monitor counting rates on the neutron target unit and gold saturation activities at the patient position were simultaneously measured through the entire duration of proton beamirradiation. The experimental results demonstrated the long-term operation of the online neutron beam monitor positioned on the neutron target unit during the entire duration of the neutron target lifespan without significant performance deterioration. A good synchronization was observed in a correlation distribution measured using the online neutron beam monitor and the gold neutron activation method. A conversion coefficient of 1.199 g with a standard deviation of 2.5% was evaluated. The neutron beam intensity irradiating on patients within an acceptable level of 5% as per the International Commission on Radiation Units and Measurements was evaluated from the online neutron counting rate at the 95% confidence level. The channel numbers of the triton peak and alpha particle edge decreased linearly owing to displacement damage and total ionizing dose effects induced mainly by thermal neutrons andphotons. Neutron doses can be accurately administered by complementing proton beam current measurements with the online neutron beam monitor. The online neutron beam monitoring technique allows monitoring fluctuations in the neutron beam intensity and tracking the degradation of the lithium target through the neutron target lifespan. Using a calibrated online neutron beam monitor, a prescribed dose can be administered in a manner similar to that in x-ray therapy, and the duration of neutron beam irradiation on the patient can be controlled in realtime.

Purpose The stochastic microdosimetric kinetic (SMK) model is one of the most sophisticated and precise models used in the estimation of the relative biological effectiveness of carbon-ion radiotherapy (CRT) and boron neutron capture therapy (BNCT). However, because of its complicated and time-consuming calculation procedures, it is nearly impractical to directly incorporate this model into a radiation treatment-planning system. Materials and methods Through the introduction of Taylor expansion (TE) or fast Fourier transform (FFT), we developed two simplified SMK models and implemented them into the Particle and Heavy Ion Transport code System (PHITS). To verify the implementation, we calculated the photon isoeffective doses in a cylindrical phantom placed in the radiation fields of passive CRT and accelerator-based BNCT. Results and discussion Our calculation suggested that both TE-based and FFT-based SMK models can reproduce the data obtained from the original SMK model very well for absorbed doses approximately below 5 Gy, whereas the TE-based SMK model overestimates the original data at higher doses. In terms of computational efficiency, the TE-based SMK model is much faster than the FFT-based SMK model. Conclusion This study enables the instantaneous calculation of the photo isoeffective dose for CRT and BNCT, considering their cellular-scale dose heterogeneities. Treatment-planning systems that use the improved PHITS as a dose-calculation engine are under development.

To realize the accelerator-based boron neutron capture therapy (BNCT) at the Cyclotron and Radioisotope Center of Tohoku University, the feasibility of a cyclotron-based BNCT was evaluated. This study focuses on optimizing the epithermal neutron field with an energy spectrum and intensity suitable for BNCT for various combinations of neutron-producing reactions and moderator materials. Neutrons emitted at 90 degrees from a thick (stopping-length) Ta target, bombarded by 50 MeV protons of 300 microA beam current, were selected as a neutron source, based on the measurement of angular distributions and neutron energy spectra. As assembly composed of iron, AlF3/Al/6LiF, and lead was chosen as moderators, based on the simulation trials using the MCNPX code. The depth dose distributions in a cylindrical phantom, calculated with the MCNPX code, showed that, within 1 h of therapeutic time, the best moderator assembly, which is 30-cm-thick iron, 39-cm-thick AlF3/Al/6LiF, and 1-cm-thick lead, provides an epithermal neutron flux of 0.7 x 10(9) [n cm(-2) s(-1)]. This results in a tumor dose of 20.9 Gy-eq at a depth of 8 cm in the phantom, which is 6.4 Gy-eq higher than that of the Brookhaven Medical Research Reactor at the equivalent condition of maximum normal tissue tolerance. The beam power of the cyclotron is 15 kW, which is much lower than other accelerator-based BNCT proposals.