M. W. Konijnenberg

Determination of dose components in phantoms irradiated with an epithermal neutron beam for boron neutron capture therapy.

The application of activation foils, thermoluminescent detectors, and ionization chambers has been investigated for the determination of the different dose components in phantoms irradiated with a mixed gamma-ray and epithermal neutron beam for boron neutron capture therapy. The thermal neutron fluence has been determined using a set of AuAl and MnNi activation foils. TLD-700 and a Mg(Ar) ionization chamber have been used for the determination of the gamma-ray dose. The dose from epithermal neutrons has been determined using a TE(TE) ionization chamber. The detector characteristics and the relative sensitivities of the various detectors to the different dose components in the phantom have been determined. The following accuracies (1 standard deviation) in the determination of the different components have been obtained: thermal neutron fluence rate: 5%; gamma-ray dose rate: 7%; epithermal neutron dose rate: 15%. These values make these detectors suitable for obtaining the complete set of clinical dosimetry data required for patient dose assessment.

Monitoring of Blood-10B Concentration for Boron Neutron Capture Therapy Using Prompt Gamma-Ray Analysis

The aim of the present study was to monitor the blood-10B concentration of laboratory dogs receiving boron neutron capture therapy, in order to obtain optimal agreement between prescribed and actual dose. A prompt gamma-ray analysis system was developed for this purpose at the High Flux Reactor in Petten. The technique was compared with inductively coupled plasma-atomic emission spectrometry and showed good agreement. A substantial variation in 10B clearance pattern after administration of borocaptate sodium was found between the different dogs. Consequently, the irradiation commencement was adjusted to the individually determined boron elimination curve. Mean blood-10B concentrations during irradiation of 25.8 +/- 2.2 micrograms/g (1 SD, n = 18) and 49.3 +/- 5.3 micrograms/g (1 SD, n = 17) were obtained for intended concentrations of 25 micrograms/g and 50 micrograms/g, respectively. These variations are a factor of two smaller than irradiations performed at a uniform post-infusion irradiation starting time. Such a careful blood-10B monitoring procedure is a prerequisite for accurately obtaining such steep dose-response curves as observed during the dog study.

Clinical dosimetry of an epithermal neutron beam for neutron capture therapy: Dose distributions under reference conditions

PURPOSE The aim of this study was to asses the dose distribution under reference conditions for the various dose components of the Petten clinical epithermal neutron beam for boron neutron capture therapy (BNCT). METHODS AND MATERIALS Activation foils and a silicon alpha-particle detector with a 6Li converter plate have been used for the determination of the thermal neutron fluence rate. The gamma-ray dose rate and the fast neutron dose rate have been determined using paired ionization chambers. Circular beam apertures of 8, 12 and 15 cm diameters have been investigated using a 15 x 15 x 15 cm3 solid polymethyl-methacrylate phantom, a water phantom of the same dimensions and a 30 x 30 x 30 cm3 water phantom at various phantom to beam-exit distances. RESULTS The effect of phantom to beam-exit distance could be modeled using an inverse square law with a virtual source to beam-exit distance of 3.0 m. At a reference phantom to beam-exit distance of 30 cm, three-dimensional dose and fluence distributions of the various dose components have been determined in the phantoms. The absolute thermal neutron fluence rate at a reference depth of 2 cm in the 15 cm water phantom increased by 43% when the field size was increased from 8 to 15 cm. Simultaneously the gamma-ray dose rate increased by 46% while the fast neutron dose rate increased by only 5%. CONCLUSION A reference treatment position at 30 cm from the beam exit allows convenient patient positioning with a relatively small increase in irradiation time compared to positions very close to the beam-exit. A more homogeneous distribution of thermal neutrons over a target volume, a higher absolute thermal neutron fluence rate and a lower contribution of the fast neutron dose to the total dose will result in improved treatment plans when using a 12 cm or 15 cm field compared to a 8 cm field. The dose distributions will be used as benchmark data for treatment planning systems for BNCT.

Dose monitoring for boron neutron capture therapy using a reactor-based epithermal neutron beam.

The aims of this study were (i) to determine the variation with time of the relevant beam parameters of a clinical reactor-based epithermal neutron beam for boron neutron capture therapy (BNCT) and (ii) to test a monitoring system for its applicability to monitor the dose delivered to the dose specification point in a patient treated with BNCT. For this purpose two fission chambers covered with Cd and two GM counters were positioned in the beam-shaping collimator assembly of the epithermal neutron beam. The monitor count rates were compared with in-phanton reference measurements of the thermal neutron fluence rate, the gamma-ray dose rate and the fast neutron dose rate, at a constant reactor power, over a period of 2 years. Differences in beam output, defined as the thermal neutron fluence rate at 2 cm depth in a phantom, of up to 15% were observed between various reactor cycles. A decrease in beam output of about 5% was observed in each reactor cycle. An unacceptable decrease of 50% in beam output due to malfunctioning of the beam filter assembly was detected. For safe and accurate treatment of patients, on-line monitoring of the beam is essential. Using the calibrated monitor system, the standard uncertainty in the total dose at depth due to variations with time of the beam output parameters has been reduced to a clinically acceptable value of 1% (one standard deviation).

Review of the Physics Calculations Performed for the BNCT Facility at the HFR Petten

The BNCT facility at the High Flux Reactor (HFR) Petten has been constructed within the existing HB11 beam tube. It consists of a combination of materials which filter the raw neutron and gamma fields emerging from the reactor removing the unwanted components, the fast and thermal neutrons plus the photons, without reducing the neutron intensity too severely. Such a device was installed in the HB11 beam tube in the summer of 1990. Prior to this event extensive calculations were undertaken to model the transport of neutrons and photons through potential filter configurations before a final optimized design was achieved. This paper provides a review of that process.

Prompt Gamma-Ray Analysis to Determine 10B Concentrations

For a successful application of BNCT knowledge of the boron pharmacokinetics is of great importance. For the future clinical trials at Petten Prompt Gamma-Ray Analysis (PGRA) will be applied to determine 10 B concentrations in patients’ blood samples. The boron concentration within the tumour volume can then be deduced from pharmacokinetic studies. With the rapidly obtained results from PGRA it will be possible to tailor the irradiation of each patient according to their individual boron pharmacokinetics.

Measurements and Calculations for Boron Neutron Capture Therapy Treatment Planning

Treatment planning aims at optimizing the radiation dose delivered over the target volume, while keeping the dose delivered to the healthy tissue at a minimum. Most efforts in treatment planning research for BNCT tend to concentrate on the second part of this aim [1, 2], as inhomogeneities in the sub-and inter-cellular boron distribution may cause considerable dose inhomogeneity. Homogeneity of the thermal and epithermal neutron fluence to the target volume should be an important goal of BNCT research.

A Semi-Empirical Method of Treatment Planning for Boron Neutron Capture Therapy

In BNCT the total dose delivered to the tumor and to the healthy tissue depends on several factors. Knowledge of the 10B distribution, the thermal neutron fluence, the epithermal neutron fluence, the fast neutron fluence and the photon dose is necessary for the calculation of the total dose delivered to all points of interest in the patient. Calculations using either Monte Carlo or deterministic codes, both commonly applied in reactor physics for neutron and photon transport calculations, have been proposed for treatment planning of BNCT1,2. Due to the large calculation times needed for these kinds of calculations, such a procedure for external photon beam treatment planning is not yet available for daily usage in radiotherapy institutions3. Therefore, little experience has been gained with these procedures in clinical situations. External photon beam treatment planning is currently based on empirical knowledge of the dose distributions under reference conditions. Beam parameters measured in a large cubical water-phantom are corrected with deterministic algorithms to calculate dose distributions in other geometries3. Treatment planning of BNCT based on Monte Carlo calculations as well as using such a semi-empirical approach is in development in the Petten-Amsterdam BNCT group4. It is the purpose of this work to investigate wether the relatively simple semi-empirical approach can be used for the treatment planning of BNCT using an epithermal neutron beam.

Boron Concentration Measurements for the Petten BNCT Project

In Petten two lines of BNCT research are conducted, one aiming at the development and construction of a clinical facility at the High Flux Reactor (1–3), and the other one studying the fundamental aspects of BNCT (3–5). For both lines the measurement of boron concentrations play a crucial role. The precondition for the clinical application of BNCT, high boron concentration in tumour cells and low concentration in normal tissue, requires insight in the pharmacokinetics of the boron compound. To understand the fundamental mechanism of BNCT, knowledge about the macroscopic distribution of boron within a tumour volume and the microscopic distribution at the cellular level are needed.

Evaluation of Dose Components for Healthy Tissue Tolerance Studies on Dogs at the HFR Petten

Before the start of clinical trials of BNCT on glioma patients at the Petten reactor, certain preconditions must be determined. In particular the tolerance of healthy brain tissue exposed to the epithermal neutron beam requires investigation. In these studies, beagle dogs have been subjected to different levels of irradiation and 10B, the latter in the form of BSH. To support this work a treatment planning tool is being developed to predict the various dose components within the treatment volume. A Monte Carlo code, MCNP1, has been used to simulate the particle transport and to predict the different dose rate distributions. The dose rates generated by MCNP are manipulated with a processing code, TREAT, to give irradiation times, peak dose positions and to display the required data in a graphical format.