Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 106 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 106 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm3. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm3. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

A computational dosimetry tool for the study of tumor doses and skin toxicities in BNCT.

A Matlab-based computational tool, named SPHERE, was developed that helps determining tumor and skin doses in BNCT treatments. It was especially designed for cutaneous melanoma treatments and, among its features, it provides a guide for the location and delineation of tumors and a visual representation of superficial dose distributions (for both tumor and normal tissues). It also generates cumulative dose-volume histograms for different volumes of interest and dose-area histograms for skin. A description of the tool is presented, as well as examples of its application.

A general tumour control probability model for non-uniform dose distributions.

Perfectly uniform dose distributions over target volumes are almost impossible to achieve in clinical practice, due to surrounding normal tissues dose constraints that are commonly imposed to treatment plans. This article introduces a new approach to compute tumour control probabilities (TCPs) under inhomogeneous dose conditions. The equivalent subvolume model presented here does not assume independence between cell responses and can be derived from any homogeneous dose TCP model. To check the consistency of this model, some natural properties are shown to hold, including the so-called uniform dose theorem. In the spirit of the equivalent uniform dose (EUD) concept introduced by Niemierko (1997, Med. Phys., 24, 103-110), the probability-EUD is defined. This concept together with the methodology introduced to compute TCPs for inhomogeneous doses is applied to different uniform dose TCP models. As expected, the TCP takes into account the whole dose distribution over the target volume, but it is influenced more strongly by the low-dose regions. Finally, the proposed methodology and other approaches to the inhomogeneous dose scenario are compared.

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.