Boron Neutron Capture Therapy Treatment Planning Research Articles

Boron Neutron Capture Therapy: Microdosimetry at Different Boron Concentrations

This paper explores the role of microdosimetry in boron neutron capture therapy (BNCT), a cancer treatment involving the selective accumulation of boron-containing compounds in cancer cells, followed by neutron irradiation. Neutron interactions with 10B induces a nuclear reaction, releasing densely ionizing particles, specifically alpha particles and recoiling lithium-7 nuclei. These particles deposit their energy within a small tissue volume, potentially targeting cancer cells while sparing healthy tissue. The microscopic energy distribution, subject to significant fluctuations due to the short particle range, influences treatment efficacy. Microdosimetry, by studying this distribution, plays a crucial role in optimizing BNCT treatment planning. The methodology employs paired tissue equivalent proportional counters (TEPCs), one with cathode walls enriched with boron and the other without. Precise assessment of boron concentration is essential, as well as the ability to extrapolate results to the actual 10B concentration within the treatment region. The effective 10B concentrations within four boronated TEPCs, containing 10, 25, 70, and 100 ppm of 10B, have been determined. Results show variations of less than 3% from nominal values. Additionally, dose enhancement due to BNC interactions was measured and found to be proportional to the 10B concentration, with a proportionality factor of 7.7 × 10−3 per ppm of boron. Based on these findings, a robust procedure is presented for assessing the impact of BNCT in the treatment region, considering potential variations in boron content relative to the TEPC used.

Investigation of the usability of cone-beam computed tomography images using digital radiography equipment for boron neutron capture therapy treatment planning in the sitting position

In boron neutron capture therapy (BNCT), treatment planning images are acquired in the recumbent position. However, treatment is occasionally performed in the sitting position. For BNCT treatment planning, we investigated the usability of cone-beam computed tomography (CBCT) images using digital radiography equipment that allows imaging in the sitting position. The dose calculation results in both CBCT and fan beam CT were in good agreement. This method will eliminate the posture difference between planning and treatment.

Evaporation process in histological tissue sections for neutron autoradiography.

The analysis of the distribution and density of nuclear tracks forming an autoradiography in a nuclear track detector (NTD) allows the determination of 10B atoms concentration and location in tissue samples from Boron Neutron Capture Therapy (BNCT) protocols. This knowledge is of great importance for BNCT dosimetry and treatment planning. Tissue sections studied with this technique are obtained by cryosectioning frozen tissue specimens. After the slicing procedure, the tissue section is put on the NTD and the sample starts drying. The thickness varies from its original value allowing more particles to reach the detector and, as the mass of the sample decreases, the boron concentration in the sample increases. So in order to determine the concentration present in the hydrated tissue, the application of corrective coefficients is required. Evaporation mechanisms as well as various factors that could affect the process of mass variation are outlined in this work. Mass evolution for tissue samples coming from BDIX rats was registered with a semimicro analytical scale and measurements were analyzed with software developed to that end. Ambient conditions were simultaneously recorded, obtaining reproducible evaporation curves. Mathematical models found in the literature were applied for the first time to this type of samples and the best fit of the experimental data was determined. The correlation coefficients and the variability of the parameters were evaluated, pointing to Page's model as the one that best represented the evaporation curves. These studies will contribute to a more precise assessment of boron concentration in tissue samples by the Neutron Autoradiography technique.

BNCT treatment planning of recurrent head-and-neck cancer using THORplan

A cooperation program on Boron Neutron Capture Therapy (BNCT) between National Tsing Hua University (NTHU) and Taipei Veterans General Hospital (TPEVGH) was established in 2008. Clinical trial of recurrent head-and-neck cancer is the goal of the program. In this study, treatment plannings of two head-and-neck cancer cases are performed using treatment planning system THORplan developed at NTHU of Taiwan. The patients are assumed to be irradiated under current THOR epithermal neutron beam. The prescription dose is 20 Gy-Eq for at least 80% of tumor volume. The irradiation time to reach the target tumor dose can be kept within 1h. The skin dose is within the limiting dose of 11 Gy-Eq. The spinal cord dose is well within the limiting dose of 10 Gy-Eq. The use of an extension collimator for easier patient positioning is helpful in reducing the dose of eye lens to within the dose limit of 5 Gy-Eq. The irradiation time, however, will increase slightly due to the increase of source-to-tumor distance. The CPU time for treatment planning calculation is ~10 h. With the use of user friendly treatment planning system THORplan, dose planning for BNCT at THOR can be easily performed.

Verification of the accuracy of BNCT treatment planning system THORplan

THORplan is a treatment planning system developed at Tsing Hua University, Taiwan, for boron neutron capture therapy (BNCT) purpose. It is recently developed with user-friendly interface using Interactive Data Language. In this article the accuracy of THORplan is verified by comparing results of Snyder phantom calculation with the analytical model results of MCNP. Neutron source from THOR epithermal neutron beam is used as the source for the calculation. The thermal neutron flux calculated by THORplan is very close to the reference results. SERA overestimates thermal neutron flux by 2–5%. NCTPlan underestimates thermal neutron flux by 4–9% in most locations. The total weighted dose calculated by THORplan is accurate to within 3% except at the tissue interface. SERA overestimates the total weighted dose at depth > 1.5 cm by 2–5%. NCTPlan underestimates the total weighted dose by ∼10% at depth > 1 cm .

Feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma from a viewpoint of dose distribution analysis

To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The (10)B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumors and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D(05) and D(95), were adopted as the representative dose for the maximum and minimum dose, respectively. When the D(05) to the normal ipsilateral lung was 5 Gy-Eq, the D(95) and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D(05) and D(95) doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.

Voxel model in BNCT treatment planning: performance analysis and improvements

In recent years, many efforts have been made to study the performance of treatment planning systems in deriving an accurate dosimetry of the complex radiation fields involved in boron neutron capture therapy (BNCT). The computational model of the patient's anatomy is one of the main factors involved in this subject. This work presents a detailed analysis of the performance of the 1 cm based voxel reconstruction approach. First, a new and improved material assignment algorithm implemented in NCTPlan treatment planning system for BNCT is described. Based on previous works, the performances of the 1 cm based voxel methods used in the MacNCTPlan and NCTPlan treatment planning systems are compared by standard simulation tests. In addition, the NCTPlan voxel model is benchmarked against in-phantom physical dosimetry of the RA-6 reactor of Argentina. This investigation shows the 1 cm resolution to be accurate enough for all reported tests, even in the extreme cases such as a parallelepiped phantom irradiated through one of its sharp edges. This accuracy can be degraded at very shallow depths in which, to improve the estimates, the anatomy images need to be positioned in a suitable way. Rules for this positioning are presented. The skin is considered one of the organs at risk in all BNCT treatments and, in the particular case of cutaneous melanoma of extremities, limits the delivered dose to the patient. Therefore, the performance of the voxel technique is deeply analysed in these shallow regions. A theoretical analysis is carried out to assess the distortion caused by homogenization and material percentage rounding processes. Then, a new strategy for the treatment of surface voxels is proposed and tested using two different irradiation problems. For a parallelepiped phantom perpendicularly irradiated with a 5 keV neutron source, the large thermal neutron fluence deviation present at shallow depths (from 54% at 0 mm depth to 5% at 4 mm depth) is reduced to 2% on average. Reassigning fluence values in the case of this phantom in angular position produced the maximum deviation in the thermal fluence to decrease from 140% to 23% at the surface of the phantom. Thus, even for the largest deviations, obtained by intentionally placing the phantom in the most disadvantageous position with respect to the voxel grid, the reassignment shows very good performance. Since these results substantially improve the performance of the 1 cm based voxel model in surface boundary regions, the proposed strategy will be implemented in future versions of the NCTPlan code.

Evaluation of carborane-containing porphyrins as tumour targeting agents for boron neutron capture therapy.

A number of carborane-containing porphyrins were administered to mice bearing subcutaneously transplanted mammary carcinomas. Administration was via serial intraperitoneal (i.p.) injections to assess their relative toxicities and tumour affinities. Three analogues of the natural porphyrin heme and four tetraphenylporphyrins (TPPs) were given at total doses of 78-245 micrograms g-1 body weight. The water-insoluble TPPs were less toxic to mice, and delivered greater amounts of boron to tumour than did the water-soluble TPPS and the heme analogues. One such compound, NiTCP-H, delivered more than 100 micrograms B g-1 to tumour tissue with a tumour:blood boron concentration ratio greater than 500:1 and a tumour: brain boron concentration ratio greater than 50:1, 4 days after the last of six i.p. injections given over 2 days. Another TPP analogue, NiTCP, delivered approximately 50 micrograms B g-1 to tumour with similar boron concentrations in normal tissues. Neither compound was toxic to mice at total doses of approximately 200 micrograms g-1 body weight. In contrast, the heme analogues were toxic and, with the exception of VCDP, delivered less boron to tumour than NiTCP and NiTCP-H. The two porphyrins with the greatest potential for application to boron neutron capture therapy (BNCT), NiTCP and NiTCP-H, yielded higher tumour:blood and tumour:brain boron concentration ratios in mice than could be achieved with p-boronophenylalanine (BPA) and sodium mercaptoundecahydrododecaborate (BSH), the compounds which are currently being used in clinical trials of BNCT in the treatment of glioblastoma. The boron delivered by each of the porphyrins tested remained in tumour tissue longer than did boron delivered by either BPA or BSH. The copper and nickel chelates of these porphyrins behave identically in vivo. The former offer the potential for imaging by 67Cu-mediated single photon emission computed tomography (SPECT) to aid BNCT treatment planning.

Methods for radiation dose distribution analysis and treatment planning in boron neutron capture therapy

This article presents a survey of recent progress in the development and application of analytical methods for calculating macroscopic and microscopic radiation dose distributions for Boron Neutron Capture Therapy (BNCT). Such calculations are an essential component of in vivo BNCT research and will ultimately also be required for human BNCT treatment planning. Calculations of macroscopic absorbed dose distributions for BNCT are more complex than for photon therapy. There are several different dose components, each of which has its own characteristic spatial distribution, linear energy transfer, and relative biological effectiveness (RBE). Three-dimensional (3-D) energy-dependent radiation transport models with a detailed treatment of particle scattering are required. Geometric descriptions for such models are typically constructed directly from medical image data and both the Monte Carlo stochastic simulation method and the discrete-ordinates deterministic approach have been successfully used to perform the necessary radiation transport calculations. Microdosimetric effects can profoundly influence the therapeutic benefit that may be attainable in BNCT. These effects must be carefully taken into account in the interpretation of experimental data, especially when correlating observed in vivo radiobiological response with absorbed radiation dose. Calculations of microdosimetric parameters for BNCT are typically performed using the Monte Carlo method to generate single-event energy deposition frequency distributions for critical targets in various cell types of interest. This information is useful in the development of apparent RBE factors, or “compound factors” for the various dose components in BNCT.