Dose homogeneity in boron neutron capture therapy using an epithermal neutron beam.

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-cm-diameter 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 10B, the brain 5 ppm 10B and the tumor 30 ppm 10B. It was found that with a single 15-cm-diameter circular beam a very inhomogenous dose distribution in a typical target volume was obtained. Applying two equally weighted opposing 15-cm-diameter 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 15- or 12-cm fields to obtain an optimal dose distribution.

Boron neutron capture therapy (BNCT): implications of neutron beam and boron compound characteristics.

The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal-neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well-characterized epithermal-neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR-1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p-Boronophenylaline Fructose (BPA-F) and a hypothetical next-generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal-neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy-tissue tolerance and a reduction in the hydrogen-recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR-1 beam has the better quality (lower hydrogen-recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR-1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully optimized.

The neutron sensitivity of dosimeters applied to boron neutron capture therapy.

To obtain a high accuracy in the dosimetry of an epithermal neutron beam used for boron neutron capture therapy (BNCT), the neutron sensitivity of dosimeters applied to determine the various dose components in-phantom has been investigated. The thermal neutron sensitivity of Mg(Ar) ionization chambers, TE(TE) ionization chambers, and thermoluminescent dosimeters (TLD) has been experimentally determined in a "pure" thermal neutron beam. Values much higher than theoretically expected were obtained and a variation up to a factor of 2.5 was found between values for the thermal neutron sensitivity of different Mg(Ar) ionization chambers of the same type. The sensitivity of the TE(TE) ionization chamber to intermediate and fast neutrons (kt) has been calculated for the neutron energy spectrum in a phantom irradiated by a clinical epithermal BNCT beam, obtained using Monte Carlo simulations. The kt value for muscle tissue ranged from 0.87 at small depths to 0.93 at larger depths in the phantom. The application of the thermal neutron sensitivities to measurements in a phantom irradiated by the epithermal BNCT beam yielded up to 17% higher gamma-ray dose rate values compared with measurements using 6Li containing caps to shield the detectors from thermal neutrons, due to a substantial perturbation of the in-phantom radiation field by the 6Li cap. The application of the new kt values resulted in a dose from intermediate and fast neutrons about 10% higher than the dose based on currently applied relative neutron sensitivities of TE(TE) chambers in BNCT beams. The resulting improvement in the accuracy of the determination of the dose from gamma rays and intermediate and fast neutrons is important in view of the required accuracy for dosimetry in radiotherapy.

A comprehensive PC-based computer model for microdosimetry of BNCT.

A computer model is described that performs microdosimetric calculations of the radiation dose delivered to tumour and normal tissue in boron neutron capture therapy (BNCT) by simulating capture reactions in a predefined three-dimensional space. The role of intracellular boron distributions and cellular dimensions on the radiation dose in clinical and experimental BNCT has been studied using a PC-based computer model. In order to calculate the radiation dose to low boron uptake cells, the extent of irradiation by boron containing adjacent cells (cross fire) is also dealt with. Radiation doses from boron and nitrogen neutron capture are converted to a biological effect by means of relative individual ion track segment efficacies, based on linear energy transfer along the particle track. A good correlation was found after comparing predicted values with previously published experimental data. A number of examples is given to illustrate the program's features.

A scintillation spectrometer for direct comparison of neutron energy spectra at high and low rates.

The energy spectrum of the HB11 beam at HFR, Petten, has previously been measured by proton and alpha recoil in hydrogen and helium gas proportional counters at power levels of a few kW. There is some doubt whether the spectrum remains the same at the much higher power of 45 MW required for therapeutic fluxes. In order to test this point, a scintillation detector has been developed at the Paul Scherrer Institute, Villingen, Switzerland. While the device is again based on the proton recoil reaction, a combination of mm-sized plastic scintillators and fast electronics will allow it to operate at both a few kW and 45 MW, permitting direct comparison of energy spectra at these very different power levels. Results of preliminary tests at LFR, Petten, are presented.

An investigation of the possibilities of BNCT treatment planning with the Monte Carlo method.

The neutron fluence distribution inside two types of water phantom have been calculated with the Monte Carlo programme MCNP for the epithermal neutron beam at the Petten Low Flux Reactor. Comparison between the calculated and the measured neutron fluence distributions showed a reasonable agreement. The influence of beam and phantom geometry on the neutron fluence distribution has been calculated. An increase of the field size leads to a somewhat deeper position of the maximum of the thermal neutron fluence distribution in the cylindrical phantom. The possible use of beam modifying devices like wedges and blocks has been tested with this model. Blocks have been modelled that can locally reduce the fast neutron skin dose by 70%.