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Purpose: Boron Neutron Capture Therapy (BNCT) is an innovative radiation therapy with significant potential in cancer treatment. This systematic review aimed to comprehensively evaluate the efficacy, safety, and applicability of BNCT across various cancer types. Methods and materials: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic search in PubMed, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and ICTRP from inception until May 27, 2023. Eligible studies were selected based on predefined criteria, and statistical analyses were performed using IBM SPSS (Statistical Package for the Social Sciences) to assess correlations between histological factors, treatment outcomes, and adverse effects. Results: The initial search identified 925 studies (498 from Scopus, 333 from PubMed, 16 from ClinicalTrials.gov, 41 from ICTRP, and 30 from Cochrane CENTRAL). After removing duplicates and applying selection criteria, 121 full-text articles were assessed, with 39 studies meeting the inclusion criteria. An additional study published in 2024 was included during the peer review process, bringing the total to 40 studies. The analysis revealed that BNCT demonstrates promising efficacy across various cancers, with a manageable safety profile. However, outcome variability and adverse effects were noted among the studies. Conclusions: BNCT shows substantial promise as a treatment modality for multiple cancer types, offering potential benefits with acceptable safety profiles. Nonetheless, further research is essential to refine its clinical application and ensure consistent safety and efficacy. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a non-invasive therapeutic technique for treating invasive malignant tumors. A tremendous amount of research is published in this area every year, and it needs to be analyzed and evaluated to measure the growth and trends of the research. This study aimed to visualize the global research landscape on BNCT based on the WoS database. This study applies co-citation and cluster analyses as a common scientometric approach to analyze the growth of research and trends in the field. Data was collected from the Web of Science database as indexed from 1980- 2021; 3639 records were retrieved. PreMap, UCINET, and NetDraw software packages were used for data visualization. As the most productive countries, the USA and Japan were in the top ranks, respectively. As the most influential researcher, BARTH, ROLF F, With the degree centrality SAKURAI, YOSHINORI, and in-betweenness centrality, MIYATAKE, SHIN-ICHI ranked first. The co-citation network of papers in the field depicted three main clusters: treatment, physics, and measurement. Social network analyses and the quality of links among papers in neutron therapy can be helpful in different aspects. Co-citation analysis depicts the internal structure of the field and helps in understanding the nature of relations among the scientometric entities. The study concludes by indicating the limitations of the present study and suggesting future research direction in the field. The results of this study may help policy-makers, researchers, practitioners, and other key stakeholders in the field.

The purpose of the study was to evaluate the efficacy of neutron therapy (NT) for salivary gland cancer and recurrent breast cancer. Material and Methods. The study included 130 patients with salivary gland cancer and 125 patients with recurrent breast cancer. Fast neutron therapy using U-120 cyclotron was given to the patients of the study group. Patients of the control group received standard radiotherapy (external beam radiotherapy). Results. Among patients with salivary gland cancer, a recurrence rate was significantly lower in patients who received a postoperative course of NT compared to patients of the control group (21.1 vs 45 %, p

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ2 =43.7; p

Mechanism of Action: External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles. History: BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use. Current Limitations and Prospects: Recently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.

Quality of life of 42 patients with locally advanced breast cancer (T2-4N0-3M0) after combined modality treatment including either neutron therapy or photon therapy was studied. The EORTC QLQ-30 (version 3.0) and EORTC QLQ -BR-23 questionnaires were used. A slight decrease in the physical and emotional state and nausea/vomiting were observed in the group of patients who received neutron therapy (n=20) as well as in the group of patients who received photon therapy (n=22). In patients of the neutron therapy group, an increase in the index of dyspnea by 6 points (with the baseline index of 15.0 ± 5.7 points) was observed. The dyspnea index decreased to 5.26 ± 2.9 points 12 months later in patients having no evidence of disease progression. Local pulmonary fibrosis was diagnosed in 2 (10 %) of 20 breast cancer patients. In photon therapy group patients, an increase in the index of dyspnea by 11 points (with the baseline index of 14.3 ± 5.1 points) was observed. In 12 months, the dyspnea index decreased to 7.1 ± 3.1 points. Local pulmonary fibrosis was diagnosed in 4 (18 %) of 22 patients. A moderate decline in the general health status was observed in both groups of patients after neutron therapy delivered to the anterior chest wall. However, all patients with locally advanced breast cancer subjectively noted the rise of the general health status 12 months after completion of treatment (78.3 ± 4.2 points, respectively). Thus, postoperative neutron therapy delivered to the anterior chest wall did not increase the frequency of complications and did not affect the quality of life of breast cancer patients.

The goal of radiotherapy is to maximize the radiation dose to abnormal cancer cells while preventing damage to healthy tissue. in neutron therapy, the optimum regime of treatment is uncertain to date.The purpose of the study to develop a set of methodological approaches that ensure the permissible frequency and severity of radiation-induced reactions in cancer patients subjected to neutron and neutron-photon therapy (NFt) using u-120 cyclotron.Material and methods. We used the dependence of the relative biological effectiveness (RBE) of neutrons on the dose and time-dose-fractionation model (tdF). the interaction of neutrons with various types of tissues was analyzed, and the algorithm for summing neutron and photon doses in neutronphoton therapy was developed.Results. Clinical studies of neutron-photon therapy showed that the developed approaches can predict and prevent serious damage to normal tissue with a satisfactory accuracy. the role of all factors influencing the nature of radiation reactions was taken into account in the computer program, which allowed the main characteristics of the planned courses of neutron-photon therapy to be obtained.

Neutron therapy was developed from neutron radiobiology experiments, and had identified a higher cell kill per unit dose and an accompanying reduction in oxygen dependency. But experts such as Hal Gray were sceptical about clinical applications, for good reasons. Gray knew that the increase in relative biological effectiveness (RBE) with dose fall-off could produce marked clinical limitations. After many years of research, this treatment did not produce the expected gains in tumour control relative to normal tissue toxicity, as predicted by Gray. More detailed reasons for this are discussed in this paper. Neutrons do not have Bragg peaks and so did not selectively spare many tissues from radiation exposure; the constant neutron RBE tumour prescription values did not represent the probable higher RBE values in late-reacting tissues with low α/β values; the inevitable increase in RBE as dose falls along a beam would also contribute to greater toxicity than in a similar megavoltage photon beam. Some tissues such as the central nervous system white matter had the highest RBEs partly because of the higher percentage hydrogen content in lipid-containing molecules. All the above factors contributed to disappointing clinical results found in a series of randomised controlled studies at many treatment centres, although at the time they were performed, neutron therapy was in a catch-up phase with photon-based treatments. Their findings are summarised along with their technical aspects and fractionation choices. Better understanding of fast neutron experiments and therapy has been gained through relatively simple mathematical models—using the biological effective dose concept and incorporating the RBEmax and RBEmin parameters (the limits of RBE at low and high dose, respectively—as shown in the Appendix). The RBE itself can then vary between these limits according to the dose per fraction used. These approaches provide useful insights into the problems that can occur in proton and ion beam therapy and how they may be optimised. This is because neutron ionisations in living tissues are mainly caused by recoil protons of energy proportional to the neutron energy: these are close to the proton energies that occur close to the Bragg peak region. To some extent, neutron RBE studies contain the highest RBE ranges found within proton and ion beams near Bragg peaks. In retrospect, neutrons were a useful radiobiological tool that has continued to inform the scientific and clinical community about the essential radiobiological principles of all forms of high linear energy transfer therapy. Neutron radiobiology and its implications should be taught on training courses and studied closely by clinicians, physicists, and biologists engaged in particle beam therapies.

Neutron therapy was developed from neutron radiobiology experiments, and had identified a higher cell kill per unit dose and an accompanying reduction in oxygen dependency. But experts such as Hal Gray were sceptical about clinical applications, for good reasons. Gray knew that the increase in relative biological effectiveness (RBE) with dose fall-off could produce marked clinical limitations. After many years of research, this treatment did not produce the expected gains in tumour control relative to normal tissue toxicity, as predicted by Gray. More detailed reasons for this are discussed in this paper. Neutrons do not have Bragg peaks and so did not selectively spare many tissues from radiation exposure; the constant neutron RBE tumour prescription values did not represent the probable higher RBE values in late-reacting tissues with low α/β values; the inevitable increase in RBE as dose falls along a beam would also contribute to greater toxicity than in a similar megavoltage photon beam. Some tissues such as the central nervous system white matter had the highest RBEs partly because of the higher percentage hydrogen content in lipid-containing molecules. All the above factors contributed to disappointing clinical results found in a series of randomised controlled studies at many treatment centres, although at the time they were performed, neutron therapy was in a catch-up phase with photon-based treatments. Their findings are summarised along with their technical aspects and fractionation choices. Better understanding of fast neutron experiments and therapy has been gained through relatively simple mathematical models—using the biological effective dose concept and incorporating the RBEmax and RBEmin parameters (the limits of RBE at low and high dose, respectively—as shown in the Appendix). The RBE itself can then vary between these limits according to the dose per fraction used. These approaches provide useful insights into the problems that can occur in proton and ion beam therapy and how they may be optimised. This is because neutron ionisations in living tissues are mainly caused by recoil protons of energy proportional to the neutron energy: these are close to the proton energies that occur close to the Bragg peak region. To some extent, neutron RBE studies contain the highest RBE ranges found within proton and ion beams near Bragg peaks. In retrospect, neutrons were a useful radiobiological tool that has continued to inform the scientific and clinical community about the essential radiobiological principles of all forms of high linear energy transfer therapy. Neutron radiobiology and its implications should be taught on training courses and studied closely by clinicians, physicists, and biologists engaged in particle beam therapies. [ABSTRACT FROM AUTHOR]

The relative biological effectiveness (RBE) of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

Background and aim: Today, electron accelerators are taken into consideration as photoneutron sources. Therefore, for maximum production of epithermal neutron flux, designing a photoneutron target is of significant importance. In this paper, the effect of thickness and geometric shape of a photoneutron target on neutron output were investigated. Methods: In this study, a pencil photon source with 13, 15, 18, 20 and 25 MeV energies and a diameter of 2 mm was investigated using Monte Carlo simulation method using MCNP code. To optimize the design of the photoneutron target, the tungsten target with various geometries and thicknesses was investigated. Results: The maximum neutron flux produced for all target geometries and thicknesses occurred at neutron energy peak of around 0.46 MeV. As the thickness increased to 2 cm, neutron flux increased and then a decreasing trend was observed. For various geometrical shapes, the determining factor in photoneutron output was the effective target thickness in the photon interaction path that increased by the increase in the area of interaction. Another factor was the angle of the photon's incidence with the target surface that resulted in a significant decrease in photoneutron output in cone-shaped targets Conclusion: Three factors including the total neutron flux, neutrons energy spectrum, and convergence of neutrons plays an important role in the selection of geometry and shape of the target that should be investigated considering beam shaping assembly (BSA) shape

Purpose: Neutrons were an active field of radiobiology at the time of publication of the first issues of the International Journal of Radiation Biology in 1959. Three back-to-back papers published by Neary and his colleagues contain key elements of interest at the time. The present article aims to put these papers into context with the discovery of the neutron 27 years previously and then give a feel for how the field has progressed to the present day. It does not intend to provide a comprehensive review of this enormous field, but rather to provide selective summaries of main driving forces and developments. Conclusions: Neutron radiobiology has continued as a vigorous field of study throughout the past 84 years. Main driving forces have included concern for protection from the harmful effects of neutrons, exploitation and optimization for cancer therapy (fast beam therapy, brachytherapy and boron capture therapy), and scientific curiosity about the mechanisms of radiation action. Effort has fluctuated as the emphasis has shifted from time to time, but all three areas remain active today. Whatever the future holds for the various types of neutron therapy, the health protection aspects will remain with us permanently because of natural environmental exposure to neutrons as well as increased additional exposures from a variety of human activities. [ABSTRACT FROM AUTHOR]

The results of the combined modality treatment including neutron therapy for patients with resistant malignant tumors were presented. Efficacy of neutron therapy was assessed using disease-free and 5-year survival rates. Neutron therapy used alone or as a combination therapy was shown to be more effective than photon therapy. A comprehensive program for the prevention and treatment of acute radiation-induced damages was devised.

Based on the fact that the parameters of the linear-quadratic model for neutron therapy were found, the comparison of single therapeutic doses in neutron therapy, calculated using the TDF (time-dose-fractionation) and linear-quadratic (LQ) models were carried out. The calculation results were shown to be in good agreement. We also compared the degree of discrepancy in results calculated using the TDF and LQ models between neutron therapy and gamma therapy. It was shown that the use of the linear-quadratic model designed for neutron therapy is capable of providing adequate control for radiation-induced tissue reactions.

From 2007 to 2011, 39 patients with locally advanced breast cancer (T2-4N0-3M0-1) received multimodality treatment including neo-and adjuvant chemotherapy, radical or segmented mastectomy, neutron therapy to the area of postoperative cicatrix and external beam radiotherapy to the areas of regional spread. Neutron therapy delivered to the area of postoperative cicatrix was well tolerated by all patients. The overall 4-year and relapse-free survival rates were 86,2 ± 6,8 % and 92,7 ± 4,9 %, respectively

The Ural Center for Neutron Therapy performs combined photon-neutron therapy for cancer patients, by applying an ELLIT-80 gamma unit and a NG-12I neutron generator. After modernization of the NG-12I generator, there was a need for redetermination of the relative biological efficiency (RBE) to optimize radiotherapy for the patients. An exotest was used to experimentally estimate RBE according to the survival criteria for stem hematopoietic cells in CBA mice after modernization of the equipment generated by the NG-12I unit with respect to the gamma radiation generated by the ELLIT-80 unit. The investigation established that the RBE factor of NG-12I unit-induced radiation determined as the ratio of equally effective doses (our study used D0) was 1.53 for an acute radiation regimen. During fractional radiation, the RBE factor of neutron radiation was 3.05. That is to say, the total neutron radiation dose replacing 20 % gamma radiation (13 Gy) in the used photon-neutron therapy regimen is 4.26 Gy. The experimental findings have led us to conclude that the previously described neuron therapy regimen may be optimized, by increasing the contribution of neutrons to the total course of radiotherapy in a definite category of patients with radioresistant tumors of the head and neck.

The authors analyzed the long-term results of standard radiotherapy (RT) in 153 patients and those of concomitant photon-neuron therapy (CPNT) in 24 patients in the combined treatment programs. The use of densely ionizing radiation in combined palliative programs for radio-resistant tumors, that include brain metastases, increased survival and improved quality of life. The survival after CPNT was 10–24 months in all the treatment programs: in the control group, that after RT and combined treatment was 4–6 and 7–11 months, respectively.

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions)., (© 2023 Institute of Physics and Engineering in Medicine.)

One of the important neutron sources for Boron Neutron Capture Therapy (BNCT) is a nuclear reactor. It needs a high flux of epithermal neutrons. The optimum conditions of the neutron spectra for BNCT are provided by the International Atomic Energy Agency (IAEA). In this paper, Miniature Neutron Source Reactor (MNSR) as a neutron source for BNCT was investigated. For this purpose, we designed a Beam Shaping Assembly (BSA) for the reactor and the neutron transport from the core of the reactor to the output windows of BSA was simulated by MCNPX code. To optimize the BSA performance, two sets of parameters should be evaluated, in-air and in-phantom parameters. For evaluating in-phantom parameters, a Snyder head phantom was used and biological dose rate and dose-depth curve were calculated in brain normal and tumor tissues. Our calculations showed that the neutron flux of the MNSR reactor can be used for BNCT, and the designed BSA in optimum conditions had a good therapeutic characteristic for BNCT.