Dose prescription in boron neutron capture therapy (original) (raw)

Dose Analysis of In Vitro and In Vivo Test for Boron Neutron Capture Therapy (BNCT)

ASEAN Journal on Science and Technology for Development, 2018

The purpose of this study was to determine the in vitro and in vivo doses of boron neutron capture cancer therapy (BNCT) using the SHIELD-HIT12A program. To be able to determine the recoil energy, the research was conducted using the Monte Carlo method. Running data obtained the value of ionization activity and recoil lost. The results showed that in vitro and in vivo doses of BNCT for soft tissue irradiation had a value of 0.312 × 10-2 Sv, which is safe and does not harm healthy body tissue around the cancer cells because it is below the threshold of 1.5 Rem or 15 × 10-3 Sv, in accordance with the provisions of the upper value permitted by the International Commission on Radiation Protection in 1966. While the comparative targets are water, the optimal target absorption dose was obtained at concentrations of 3.232 × 10-3 Gy. The dose of carbon equivalent in water with the type of thermal neutron radiation was 16.16 × 10-3 Sv; this dose is classified as unsafe.

Dose Homogeneity in Boron Neutron Capture Therapy Using an Epithermal Neutron Beam

Radiation Research, 1995

Simulation models based on the neutron and photon Monte Carlo code MCNP were used to study the therapeutic possibilities of the HB11 epithermal neutron beam at the High Flux Reactor in Petten. Irradiations were simulated in two types of phantoms filled with water or tissue-equivalent material for benchmark treatment planning calculations. In a cuboid phantom the influence of different field sizes on the thermal-neutron-induced dose distribution was investigated. Various shapes of collimators were studied to test their efficacy in optimizing the thermal-neutron distribution over a planning target volume and healthy tissues. Using circular collimators of 8, 12 and 15 cm diameter it was shown that with the 15-cm field a relatively larger volume within 85% of the maximum neutron-induced dose was obtained than with the 8-or 12-cmdiameter field. However, even for this large field the maximum diameter of this volume was 7.5 cm. In an ellipsoid head phantom the neutron-induced dose was calculated assuming the skull to contain 10 ppm '0B, the brain 5 ppm 10B and the tumor 30 ppm '1B. It was found that with a single 15-cm-diameter circular beam a very inhomogeneous dose distribution in a typical target volume was obtained. Applying two equally weighted opposing 15-cmdiameter fields, however, a dose homogeneity within ?10% in this planning target volume was obtained. The dose in the surrounding healthy brain tissue is 30% at maximum of the dose in the center of the target volume. Contrary to the situation for the 8-cm field, combining four fields of 15 cm diameter gave no large improvement of the dose homogeneity over the target volume or a lower maximum dose in the healthy brain. Dose-volume histograms were evaluated for the planning target volume as well as for the healthy brain to compare different irradiation techniques, yielding a graphical confirmation of the above conclusions. Therapy with BNCT on brain tumors must be performed either with an 8-cm four-field irradiation or with two opposing 15or 12-cm fields to obtain an optimal dose distribution. @

Boron Neutron Capture Therapy: Effects of Split Dose and Overall Treatment Time

Journal of Neuro-oncology, 2001

New clinical protocols are being developed that will entail the administration of considerably higher doses of the boron delivery agent boronophenylalanine (BPA) than those in current clinical use. Fractionation (2 or 4 fractions) of BPA mediated boron neutron capture therapy (BNCT) is also under consideration at some clinical centres. Given the considerably higher infusion volumes that will be entailed in the delivery of BPA in the new high dosage protocols, there will be a requirement to extend the gap between fractions to 2 or more days. In order to assess the effects of a 2 fraction protocol on the therapeutic efficacy of BPA mediated BNCT, a series of split dose irradiations (two equal fractions) were undertaken using the rat intracranially implanted 9L gliosarcoma model. A single dose exposure to BPA mediated BNCT of 3.0 Gy resulted in long term survival levels of 50%. Survival levels increased to 71% and 77% with a 3 and 5 day gap between dose fractions (two equal fractions), respectively, using the same total dose. A further increase in the time interval between dose fractions to 7 days resulted in a reduction in survival to 36%. However, there was no significant difference between the single dose and the 3, 5 and 7 day survival data (P > 0.1) The difference between the 5 and 7 day split dose survival data was of border-line significance (P = 0.05). It is anticipated that mucositis, could become a potential problem in future BNCT clinical protocols involving higher doses, larger field sizes or multiple fields. The potential sparing of the oral mucosa, due to repopulation during the interval between the two fractions, was investigated using a series of split dose BPA mediated BNC irradiations. The ventral surface of the rat tongue was utilised as a model for oral mucosa. The ED50 (50% incidence) values for the ulceration end point were 3.0±0.1,3.2±0.1,3.0±0.1 and 3.6±0.1 Gy, for 3, 5, 7 and 9 day splits between doses, respectively. It is evident from this data that there were no significant changes in the ED50 (p < 0.001) until the 9 day dose split, when the ED50 value was 20% higher than the ED50 value after a 7 day split. It was concluded that the two fraction BNCT protocol, with dose splits of up to 5 days, did not diminish the therapeutic response of the rat 9L gliosarcoma, when compared with a single dose BNCT protocol. Tolerance of the oral mucosa to BNC irradiation was not increased until there was a 9 day gap between fractions. However, the beneficial effects of dose sparing at this time interval between doses, would probably be counteracted by a reduction in the therapeutic effectiveness of the BNCT modality, due to repopulation of tumour clonogens between doses.

Implications for clinical treatment from the micrometer site dosimetric calculations in boron neutron capture therapy

Applied Radiation and Isotopes, 2009

Boron neutron capture therapy has now been used for several malignancies. Most clinical trials have addressed its use for the treatment of glioblastoma multiforme. A few trials have focused on the treatment of malignant melanoma with brain metastases. Trial results for the treatment of glioblastoma multiforme have been encouraging, but have not achieved the success anticipated. Results of trials for the treatment of malignant melanoma have been very promising, though with too few patients for conclusions to be drawn. Subsequent to these trials, regimens for undifferentiated thyroid carcinoma, hepatic metastases from adenocarcinoma of the colon, and head and neck malignancies have been developed. These tumors have also responded well to boron neutron capture therapy. Glioblastoma is an infiltrative tumor with distant individual tumor cells that might create a mechanism for therapeutic failure though recurrences are often local. The microdosimetry of boron neutron capture therapy can provide an explanation for this observation. Codes written to examine the micrometer scale energy deposition in boron neutron capture therapy have been used to explore the effects of near neighbor cells. Near neighbor cells can contribute a significantly increased dose depending on the geometric relationships. Different geometries demonstrate that tumors which grow by direct extension have a greater near neighbor effect, whereas infiltrative tumors lose this near neighbor dose which can be a significant decrease in dose to the cells that do not achieve optimal boron loading. This understanding helps to explain prior trial results and implies that tumors with small, closely packed cells that grow by direct extension will be the most amenable to boron neutron capture therapy.

Dosimetry and dose planning in boron neutron capture therapy : Monte Carlo studies

2012

Boron neutron capture therapy (BNCT) is a biologically targeted radiotherapy modality. So far, 249 cancer patients have received BNCT at the Finnish Research Reactor 1 (FiR 1) in Finland. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues, and on the accuracy of the doses. At FiR 1, patient dose calculations are performed with the Monte Carlo (MC) -based treatmentplanning system (TPS), Simulation Environment for Radiotherapy Applications (SERA). Initially, BNCT was applied to head and neck cancer, brain tumors, and malignant melanoma. To evaluate the applicability of the new target tumors for BNCT, calculation dosimetry studies are needed. So far, clinical BNCT has been performed with the neutrons from a nuclear reactor, while an accelerator based neutron sources applicable for hospital operation would be preferable. In this thesis, BNCT patient dose calculation practice in Finland was evaluated against referen...

A history of boron neutron capture therapy of brain tumours: Postulation of a brain radiation dose tolerance limit

Brain

Boron neutron capture therapy (BNCT) is a form of radiation therapy mediated by the short-range (less than 10 fim) energetic alpha ( 4 He) and lithium-7 ( 7 Li) ionizing particles that result from the prompt disintegration by slow neutrons of the stable-(nonradioactive) nucleus boron-10 ( 10 B). Recent advances in radiobiological and toxicological evaluation of tumour-affirutive boron-containing drugs and in optimization of the energies of neutrons in the incident beam have spurred interest in BNCT. This article presents a history of BNCT that emphasizes studies in the USA. A new dosimetric analysis of the 1959-1961 clinical trials of BNCT at Brookhaven National Laboratory is also presented. This analysis yields an acute radiation dose tolerance limit estimate of -10 Gy-Eq to the capillary endothelium of human basal ganglia from BNCT. (Gy-Eq: Gray-equivalent, or relative biological effectiveness of a radiation component multiplied by the physical dose of the component (Gy), summed over the component kinds of radiation.)

An international dosimetry exchange for boron neutron capture therapy, Part I: Absorbed dose measurements

Medical Physics, 2005

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step ͑Part I͒ the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik ͑Sweden͒, VTT Espoo ͑Finland͒, and the Nuclear Research Institute ͑NRI͒ at Rez ͑Czech Republic͒. A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 g g −1 that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

A comparison of the dose RBE and the biological dosimetry approaches for treatment planning in BNCT

Treatment planning for clinical trials with boron neutron capture therapy (BNCT) is complicated substantially by the fact that the radiation field generated by the activating external neutron beam is composed of several different types of radiation, i.e., fast neutrons, recoil protons from elastic collisions with hydrogen, gamma rays from the reactor and from neutron capture by body hydrogen, protons from nitrogen capture, and the products of the NCT interaction. Furthermore, the relative contribution of each type of radiation varies with depth in tissue. Because each of these radiations has its own RBE, and the RBE of the fast neutron component will not be constant as the neutron spectrum changes with depth, the problem of predicting the severity of the biological effect, in depth, becomes complex indeed. In order to attack this problem, Monte Carlo calculations of dose, checked against benchmark measurements, are employed. Two approaches are then used to assess the severity of the...

The essential role of radiobiological figures of merit for the assessment and comparison of beam performances in boron neutron capture therapy

Physica Medica, 2019

Boron Neutron Capture Therapy (BNCT) is a treatment modality that uses an external neutron beam to selectively inactive boron10-loaded tumor cells. This work presents the development and innovative use of radiobiological probability models to adequately evaluate and compare the therapeutic potential and versatility of beams presenting different neutron energy spectra. M&M: Aforementioned characteristics, collectively refer to as the performance of a beam, were defined on the basis of radiobiological probability models for the first time in BNCT. A model of uncomplicated tumor control probability (UTCP) for HN cancer was introduced. This model considers a NTCP able to predict severe mucositis and a TCP for non-uniform doses derived herein. A systematic study comprising a simplified HN cancer model is presented as a practical application of the introduced radiobiological figures of merit (FOM) for assessing and comparing the performance of different clinical beams. Applications involving treated HN cancer patients were also analyzed. Results: The maximum UTCP proved suitable and sensitive to assess the performance of a beam, revealing particularities of the studied sources that the physical FOMs do not highlight. The radiobiological FOMs evaluated in patients showed to be useful tools both for retrospective analysis of the BNCT treatments, and for prospective studies of beam optimization and feasibility. Conclusions: The presented developments and applications demonstrated that it is possible to assess and compare performances of completely different beams fairly and adequately by assessing the radiobiological FOM UTCP. Thus, this figure would be a practical and essential aid to guide treatment decisions.