Accelerator-based Boron Neutron Capture Therapy Research Articles

Evaluating optimal quality assurance and quality control conditions of activation measurements at the accelerator-based boron neutron capture therapy system employing a lithium target

Evaluating neutron output is important to ensure proper dose delivery for patients in boron neutron capture therapy (BNCT). It requires efficient quality assurance (QA) and quality control (QC) while maintaining measurement accuracy. This study investigated the optimal measurement conditions for QA/QC of activation measurements using a high-purity germanium (HP-Ge) detector in an accelerator-based boron neutron capture therapy (AB-BNCT) system employing a lithium target. The QA/QC uncertainty of the activation measurement was evaluated based on counts, reproducibility, and standard radiation source uncertainties. Measurements in a polymethyl methacrylate (PMMA) cylindrical phantom using aluminum-manganese (Al–Mn) foils and aluminum-gold (Al–Au) foils and measurements in a water phantom using gold wire with and without cadmium cover were performed to determine the optimal measurement conditions. The QA/QC uncertainties of the activation measurements were 4.5% for Au and 4.6% for Mn. The optimum irradiation proton charge and measurement time were determined to be 36 C and 900 s for measurements in a PMMA cylindrical phantom, 7.0 C and 900 s for gold wire measurements in a water phantom, and 54 C and 900 s at 0–2.2 cm depth and 3,600 s at deeper depths for gold wire measurements with cadmium cover. Our results serve as a reference for determining measurement conditions when performing QA/QC of activation measurements using HP-Ge detectors at an AB-BNCT employing a lithium target.

A method for delivering the required neutron fluence in an accelerator-based boron neutron capture therapy system employing a lithium target

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

Influence mechanism of lithium surface oxidation on neutron yield of lithium target for accelerator-based neutron source

Lithium is generally adopted as the target to generate epithermal neutrons based on 7Li(p,n)7Be nuclear reaction for the application of accelerator-based boron neutron capture therapy (AB-BNCT). The stability of neutron yields and neutron energy spectrum are key factors for the therapeutic effects of the AB-BNCT. Owing to the active chemical properties of lithium, the surface oxidation formation of lithium may influence the soundness of the target system and the stability of neutron yields. Experimental and simulation methods were performed for a better understanding of the passivation layer formation after air exposure and the influence of the passivation layer on the neutron yield and energy spectrum. On one hand, X-ray photoelectron spectroscopy was adopted to study the chemical states of lithium after air exposure. On the other hand, particle and heavy ion transport code system (PHITS) was used to evaluate the effect of surface chemical states variation on neutron yield and energy spectrum. The simulation results indicate that the formation of Li2O with a thickness of 2 μm could mainly influence the neutron yields at the neutron emission angle of 20–90° with a maximum reduction of ∼ 10.4%.

Field tuning study and RF electromagnetic design of a continuous-wave RFQ with ramped inter-vane voltage for AB-BNCT

A compact radio frequency quadrupole (RFQ) linac for accelerator-based boron neutron capture therapy is being developed at Xi'an Jiaotong University. By adopting a ramped inter-vane voltage in the beam dynamics design, the RFQ could accelerate a continuous wave proton beam to 2.6 MeV over a length of 4 m, effectively decreasing costs and saving space. To meet the beam-dynamics requirements, both the vane width and undercut were optimized during the electromagnetic design. In addition, π-mode stabilization loops were included to increase the mode separation, and fixed tuners with varying diameters were installed to obtain close frequency-tuning sensitivity. It was established that the field unflatness can be controlled within ±1.5% when all tuners remain at their nominal insertion depth. Optimized cooling-channel design was completed, and multi-physics analysis was conducted. The water tuning coefficients of the vane and wall channels were analyzed to establish the ability to fine tune the RFQ during operation.

Effects of neutron sources and moderator materials on therapeutic dose delivery to deep-seated lesions in proton accelerator-based boron neutron capture therapy

This study aimed to identify the optimal conditions for delivering sufficient doses to deep-seated lesions within short irradiation times for two boron carriers of different T/N ratios. The therapeutic depth and irradiation time of a neutron beam for beam shaping assemblies (BSAs) with a Li or Be target and a MgF2 or CaF2 moderator were examined with the fast-neutron dose per epithermal neutron (FNR) as a parameter. When T/N = 3.61, the therapeutic depth was almost saturated at an FNR of about 10 × 10–13 Gy·cm2; when the FNR value was about 10 × 10–13 Gy·cm2, the therapeutic depth of the neutron beam for the BSA with a Be target and a MgF2 moderator was almost identical to that for the neutron beam for the BSA with a Be target and a CaF2 moderator, and slightly greater than those for the neutron beams for the BSAs with a Li target and a MgF2 or CaF2 moderator; moreover, the irradiation time of the neutron beam for the BSA with a Be target and a MgF2 moderator was shorter than that for the neutron beam for the BSA with a Be target and a CaF2 moderator. When T/N = 100, the therapeutic depths of the neutron beams for the BSAs varied greatly depending on the FNR, and were greater than the corresponding values for T/N = 3.61. We therefore concluded that the BSA with a Be target and a MgF2 moderator that produced a neutron beam with an FNR of about 10 × 10–13 Gy·cm2 is optimal for delivering sufficient doses to deep-seated lesions in short irradiation times when T/N = 3.61, and stricter control over FNR is required when T/N = 100.

A new proton injector based on PKU-type 2.45GHz PMECR ion source for BNCT facility

A first fully domestically Accelerator-based boron neutron capture therapy demonstration device(AB-BNCT) located in Yangtze River Delta region is being build recently. The project is held by “Xi’an Jiaotong University-Huzhou Neutron Science Laboratory” joint lab established by Xi’an Jiaotong University and Huzhou Industrial Group. The AB-BNCT facility requires a proton beam of 30 mA@40 keV at RFQ entrance, with its beam duty cycle between 0.5%-100%, and its normalized root mean square emittance less than 0.2 π.mm.mrad. Ion source group of Peking University (PKU) is in charge of the proton ion source and its low energy beam transportation section (LEBT). A PKU type compact permanent magnet 2.45 GHz ECR ion source (PKU-Type PMECR) and a two solenoid LEBT is under development for this purpose. So far, the PMECR ion source conditioning is complete and all parameters are better than required for this facility. The details will be presented in the present paper.

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 μSv h-1 after 13 min of shutdown meets the dose rate limit of 2.5 μSv h-1, at which point it is safe for workers to enter the treatment room area.

Experimental designs for radiobiological characterization of an accelerator-based BNCT system in preclinical studies

Experimental designs for radiobiological characterization of an accelerator-based BNCT system in preclinical studies

Preparation and properties of chromium protective coatings on lithium targets for accelerator-based neutron sources

Chromium (Cr) with its high antioxidative properties acts as a protective layer for lithium targets in accelerator-based boron neutron capture therapy (AB-BNCT). Employing a controlled variable method, this study explores the impact of magnetron sputtering parameters (sputtering power, argon flow, and sputtering pressure) on the surface morphology and crystalline structure of Cr films. Under the optimal preparation parameters (300W, 20ssm, 0.5Pa), a dense and uniform film with a (110) phase was formed, and a compact Cr2O3 layer developed during air exposure. A 1 μm Cr coating provided effective protection for approximately 2 h, and increased thickness further improved the protection. Monte Carlo simulations revealed that a 1 μm Cr coating caused around 1.83% energy loss and 5.54% neutron yield reduction for 2.8 MeV protons, meeting AB-BNCT requirements with minimal impact on neutron angular distribution. This study demonstrates that by investigating the effects of magnetron sputtering preparation parameters on the surface morphology and crystalline structure of Cr coatings, optimal preparation parameters can be selected. The fabrication of a uniform and dense 1 μm Cr protective layer on a lithium target effectively prevents the degradation of the lithium target during short-term exposure to air, thereby enhancing its transportability and ease of handling.

Double-layered beam shaping assembly design based on intelligent optimization method coupling neural network and genetic algorithm for BNCT

The beam shaping assembly (BSA) plays a crucial role in the facility of accelerator-based boron neutron capture therapy (AB-BNCT). The quality of the neutron beam utilized for treatment is directly influenced by the design of the BSA. However, conventional step-by-step optimization approaches often encounter challenges in achieving the global optimal solution, as they tend to converge towards local optima. To address this issue, this study proposed an intelligent optimization method that combines neural network and genetic algorithm. The proposed method was applied to optimize a double-layered BSA based on the neutron source resulting from a lithium target bombarding by a 2.8 MeV, 20 mA proton beam. The obtained optimal BSA solution parameters well met the IAEA-TECDOC-1223 report, while also exhibiting significantly higher epithermal neutron flux compared to alternative BSA designs. The performance of the epithermal neutron beam was assessed by calculating the dose distribution and clinical parameters in the Snyder head phantom. The findings suggest that this beam exhibits promising therapeutic potential for treating tumors.

Performance evaluation of a 71Ga(n,γ)72Ga reaction-based epithermal neutron flux detector at an AB-BNCT device

The 71Ga(n,γ)72Ga reaction-based epithermal neutron flux detectors are novel instruments developed to measure the epithermal neutron flux of boron neutron capture therapy (BNCT) treatment beams. In this study, a spherical epithermal neutron flux detector using 71Ga(n,γ)72Ga reaction was prototyped. The performance of the detector was experimentally evaluated at an accelerator-based BNCT (AB-BNCT) device developed by Lanzhou University, China. Based on the experimental results and related analysis, we demonstrated that the detector is a reliable tool for the quality assurance of BNCT treatment beams.

A study on out-of-field leakage of an accelerator-based neutron beam for boron neutron capture therapy.

More and more accelerator-based boron neutron capture therapy (AB-BNCT) facilities are under the construction or commissioning stage, and the neutron beam characteristic measurements at each facility will start soon. In addition to the in-field neutron beam properties, the leakage of neutron beam is also important, which is related to the side effects of the patient. In the Virtual Technical Meeting on Advances in Boron Neutron Capture Therapy held by International Atomic Energy Agency (IAEA) in July 2020, the issue of the out-of-field leakage in BNCT was addressed. Heron Neutron Medical Corporation has been working on the beam design for China Medical University Hsinchu Hospital AB-BNCT research center. To evaluate the out-of-field leakage, both beam profile analysis and whole-body dose calculation are performed. An Oak Ridge National Laboratory (ORNL) Medical Internal Radiation Dose (MIRD) mathematical phantom is used to calculate the whole-body dose. For the estimated irradiation time which is set to be the time required for 80% of tumor dose to reach 20 Gy-w, the relative biological effectiveness weighted dose of abdomen region is less than 40 mGy-w and the whole-body dose is 104 mSv. The beam profile calculational result shows that the neutron ambient dose equivalent at 15 cm from the field edge is 11 mSv/Gy-w and drops to 5 mSv/Gy-w at 26 cm from the field edge. The gamma ray ambient dose equivalent is less than 1 mSv/Gy-w starting from 10 cm from the field edge. Although the neutron out-of-field leakage of the beam design is higher than that of the initially proposed guideline by IAEA in 2020, the whole-body dose, however, is reasonably low. Both the whole-body dose evaluation and the beam profile analysis are useful in the beam design consideration. The whole-body dose calculation together with the beam profile analysis can also be helpful in reaching an acceptable recommendation for the out-of-field leakage for BNCT neutron beam, a job wished to be accomplished in the near future as proposed in the 2023 IAEA's report on Advances in Boron Neutron Capture Therapy.

Conceptional design of an adjustable moderator for BNCT based on a neutron source of 2.8 MeV proton bombarding with Li target

Beam shaping assembly (BSA) is a vital component in Boron Neutron Capture Therapy (BNCT) for obtaining epithermal neutron beams. Several feasible designs of BSA for accelerator-based BNCT (AB-BNCT) neutron source are carried out based on neutrons by bombarding a natural lithium target with 10 mA, 2.8 MeV proton beams. The calculation results demonstrate that a thickness of 45 cm is appropriate for general moderators referring to the therapeutic parameter of Advanced Depth (AD). A series of optimizations are performed and two results are confirmed: One is that employing the configuration of MgF2 and FLUENTAL combined by 1:1 could improve the therapeutic rate (TR) of tumors at a depth of middle region, and the other one is that the TR of superficial tumors can be increased by adding a 5 cm thick boron-11 secondary moderator at the end of general moderators. As a result, an innovative conception of an adjustable moderator is recommended to BNCT. Compared to the MgF2 moderator with a fixed thickness of 45 cm, the TR value can be improved by a maximum of 47.7 % by using the adjustable moderator. Furthermore, the configuration of adjustable moderator has been designed with regulation method for treating tumors of different depths.

10082-RT-1 LONG-TERM RESULTS OF A BNCT PHASE II CLINICAL TRIAL USING AN ACCELERATOR-BASED NEUTRON SOURCE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract PURPOSE Accelerator-based neutron sources have received regulatory approval and boron neutron capture therapy (BNCT) for head and neck cancer has been introduced into clinical treatment in earnest. BNCT is a radiotherapy with cell-selective characteristics, and its application to highly invasive malignant gliomas (MG) is the origin of its development. This study reports the long-term results of a phase II study of accelerator-based BNCT (AB-BNCT) using a cyclotron-based neutron source (BNCT30) and a boronophenylalanine product (SPM-011) in patients with recurrent MG. METHODS A phase 2 clinical trial (JG002) in 27 patients with recurrent malignant glioma (MG) (24 with glioblastoma (GB)) was conducted using SPM-011 and BNCT30. Eligibility criteria were radiation re-irradiation with MG not previously treated with bevacizumab and patients relapsing after standard of care (radiotherapy and chemotherapy with temozolomide). The primary endpoint was one-year survival from BNCT treatment, and secondary endpoints included median overall survival (mOS) and median progression-free survival (mPFS). The 1-year survival and mOS of patients with relapsed GB in JG002 were 79.2% (95% CI: 57.0-90.8) and 18.7 months, respectively. The current long-term observation resulted in an mOS of 19.2 months (95% CI: 13.1-24.8) and survival rates of 33.3 and 20.8% at 2 and 3 years from treatment, respectively. The adverse event was cerebral edema, and 21 of the 27 patients received bevacizumab treatment after decision of disease progression (PD) on imaging. CONCLUSION AB-BNCT showed an acceptable safety and survival benefit in relapsed MG, predominantly GB. Following BNCT treatment, the tumor may have shown a contrast enhancement in the irradiated field, with associated brain edema. BNCT showed a survival benefit in patients with recurrent malignant gliomas, even in the long term.

Coin-structured tunable beam shaping assembly design for accelerator-based boron neutron capture therapy for tumors at different depths and sizes

Coin-structured tunable beam shaping assembly design for accelerator-based boron neutron capture therapy for tumors at different depths and sizes

Induced radioactivity in AB-BNCT: an analysis of the different facilities worldwide

The global effort to establish Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) facilities involves various accelerator technologies and neutron-producing targets, each characterized by different properties of the primary beam and neutron spectra they generate. With an emphasis on long-term sustainability, it is essential to minimize the production of residual radioactivity to the lowest possible level, particularly given their intended use in a hospital environment. This paper aims to quantitatively assess the residual radioactivity in these facilities, taking into account both primary and secondary activation. Primary activation primarily arises from the interaction of the proton or deuteron beam and the neutron-producing target. Secondary activation results from neutron-induced reactions on the elements exposed to the neutron flux, with the Beam Shaping Assembly (BSA) being the most exposed one. To assess activation, we evaluated a representative group of target-BSA configurations. Primary activation was calculated based on cross-sectional data and the corresponding target materials. Neutron activation was assessed using Monte Carlo simulations with the MCNP 6.1 code. Regarding target activation, our findings indicate that 9Be targets working with protons of less than 10 MeV represent the cleanest option, while 7Li targets working with protons lead to the highest activation levels. As for BSA activation, the neutron energy is a crucial factor. In the case of standard BSA materials, higher neutron energy results in an increased number of potential reactions that produce radioactive products. Additionally, our findings suggest that radioactivity induced by impurities and minor components in alloyed materials cannot be disregarded and must be taken into account in radioactivity calculations. In summary, this research provides a comprehensive analysis of activation of the commonly used targets and BSA materials, aimed at contributing to the optimization of AB-BNCT facilities from a radiological perspective.

RADT-37. INTERIM RESULTS OF ACCELERATOR-BASED BORON NEUTRON CAPTURE THERAPY, RANDOMIZED CONTROLLED TRIAL FOR RECURRENT AND REFRACTORY HIGH-GRADE MENINGIOMAS

Abstract BACKGROUND High-grade meningiomas (HGMs) recurred after X-ray treatment showed 5.2 months as median progression free survival (mPFS) and only 24.6 months as median overall survival (mOS) from the literatures. Recently, we showed much more excellent OS and PFS using reactor-based boron neutron capture therapy (BNCT) (Neuro-Oncology 24:90-98, 2022). Based on these data, we started “A phase II investigator-lead RCT using accelerator-based BNCT system for refractory recurrent high-grade meningioma”, with the aid of Japanese governmental financial support. METHODS We prepared 2 study arms, BNCT test treatment arm (12 subjects) and control best supportive care arm (6 subjects) in RCT fashion. PFS judged by third party committee was set-up as primary endpoint and PFS judged by investigators themselves and OS of BNCT arm were set-up as secondary endpoints. To diminish ethical problems of this RCT, rescue BNCT is permitted for control group patients, if they showed progress disease during the observation period. Macdonald criteria was adopted for assessment. The first patient-in was August 2019 and the last patient-in was August 2021. Interim results of this trial: Three and two grade 3 subjects were included in BNCT and control arm, respectively. Others were grade 2 subjects. As of April 20, 2023, mPFS judged by investigators showed 90 weeks and 8 weeks for BNCT and control arm, respectively (P = 0.0004). OS-2 year rates of BNCT and control arms are 91.7% and 25%, respectively (p = 0.01) CONCLUSION Primary endpoint, mPFS judged by third party committee is still being closed and unknown, so far, until the end of the trial (August 2024). With regard to secondary endpoints, there are marked differences in both arms in mPFS judged by investigators. Also, OS in BNCT arm is extremely excellent in comparison with EORTC RCT of “trabectedine” and PD-1 blockade reports, just recently appeared.

Effect of magnetron sputtering power on structure and properties of Ta films on Cu substrate of neutron production target for accelerator-based boron neutron capture therapy (AB-BNCT)

Tantalum, with a high hydrogen diffusion coefficient, can be used as an interlayer for neutron production target in Accelerator-based Boron Neutron Capture Therapy (AB-BNCT) to prevent hydrogen embrittlement of Cu substrate. Magnetron sputtering technique was employed to deposit Ta films on the Cu Substrate, with sputtering power being a key parameter. This study investigated the effect of sputtering power on the properties of Ta films deposited on Cu substrate through several methods and Monte Carlo simulations (PHITS and SRIM). A turning point was observed at 250 W, beyond and below which increasing sputtering power led to the increase of Ta film thickness, potentially due to changes in the crystalline structure during deposition. The Ta film exhibited superior surface performance at sputtering powers of 300 W and 350 W. The chemical state of Ta was not affected by sputtering power. Thermal conductivity was observed to decrease after Ta deposition. The thickness of Ta film in this study had a negligible effect on neutron energy spectra and angular distribution. Moreover, a Ta film thickness of 20 μm prevented proton deposition and hydrogen embrittlement in the Cu substrate. These findings have important implications for designing and fabricating neutron production target in AB-BNCT.

Experimental validation of a BNCT epithermal neutron flux detector using 55Mn(n,γ)56Mn reaction at an accelerator-based BNCT facility

The epithermal neutron flux is one of the key beam quality factors for boron neutron capture therapy (BNCT), its accurate measurement is extremely important as it is directly related to the beam quality assurance (QA) and radiation dose evaluation in BNCT. In this work, a spherical BNCT epithermal neutron flux detector using 55Mn(n,γ)56Mn reaction was redesigned and prototyped. The detector prototype was experimentally validated at the accelerator-based BNCT (AB-BNCT) facility developed by Lanzhou University. The experimental results and related analysis indicate that the detector can be a reliable tool for the QA of BNCT treatment beam.

Current development status of accelerator-based neutron source for boron neutron capture therapy

Recently, progress in technology for accelerator-based neutron sources has increased attention regarding boron neutron capture therapy (BNCT). BNCT is a type of radiotherapy that combines neutrons and boron drugs and is expected to be used in the treatment of refractory and recurrent cancers. Owing to the need for high-intensity neutrons in treatment, compact accelerator-based neutron sources applicable to BNCT are being developed worldwide. These current projects utilize cyclotrons, linear accelerators, and electrostatic accelerators as accelerators for BNCT devices. Beryllium and lithium are the main target materials for neutron generation. The accelerators for BNCT device are required to accelerate charged particles with an average current ranging from a few milliamperes to a few tens of milliamperes in order to generate neutrons of sufficient intensity for the treatment. Moreover, the target systems require technologies and mechanisms that can withstand the large heat load produced by high-power beam irradiation and prevent blistering. This review outlines and explains the accelerator neutron sources for BNCT and the requirements for the components of each device, such as the accelerator, target material, and beam shaping assembly. In addition, various development projects for accelerator-based BNCT devices worldwide are introduced.