Dosimetric evaluation and beam characterization of pair production enhanced radiotherapy (PPER) with the use of organometallics.

The current study evaluates dosimetric and spectral effects when platinum (Pt)-based chemotherapeutics and less toxic tungstophosphoric-acid (TPA) organometallics are present during x-ray radiotherapy. We hypothesize that the use of high energy photon beams (i.e. 18 MV) will increase absorbed dose due to increased pair production from high-Z elements and thus result in additional tumor cell kill. EGSnrc code was used to examine the contribution of pair production to dose in the presence of the high-Z material (TPA, Pt mixtures and tungsten, W) as a function of beam energy. Variables included different concentrations (100 µmolar, 1 mmolar), depths (5 mm, 10 cm), thicknesses (5 mm, 5 cm) and energies (6, 18 MV). Overall, for the deeper depth, the 511 keV photon fluence increase was up 31% (18 MV-1 mmolar) while at 6 MV it was between 10%-11% depending on the concentration. For the shallower depth, 18 MV fluence increase was up 14.6% (1 mmolar) and 18.6% (1 mmolar) for the 6 MV. The dose enhancement effect due to pair production was up 25%-30% and a total 33%-58% depending on the depth. The benefit related to pair production was more for 18 MV and under conditions that simulated a realistic clinical setup. While part of the effect could be attributed to photoabsorption, a significant contribution of dose could result from pair production. Experimental clonogenic survival assay was consistent with the theory in that the low dose shoulder region of a cell survival curve was reduced using TPA and 18 MV compared with TPA and 6 MV or compared with no TPA and 18 MV; RBE was approximately 2 at the dose commonly used in conventional fractionated clinical radiotherapy. This suggests a potential new strategy for dose enhancement based on pair production using higher energy beamlines.

Low-Z linac targets for low-MV gold nanoparticle radiation therapy.

PURPOSE: To investigate the potential of low-Z/low-MV (low-Z) linac targets for gold nanoparticle radiotherapy (GNPT) and to determine the microscopic dose enhancement ratio (DER) due to GNP for the alternative beamlines. In addition, to evaluate the degradation of dose enhancement arising from the increased attenuation of x rays and larger skin dose in water for the low-MV beams compared to the standard linac. METHODS: Monte Carlo simulations were used to compute dose and DER for various flattening-filter-free beams (2.5, 4, 6.5 MV). Target materials were beryllium, diamond, and tungsten-copper high-Z target. Target thicknesses were selected based on 20%, 60%, 70%, and 80% of the continuous slowing down approximation electron ranges for a given target material and energy. Evaluation of the microscopic DER was carried out for 100 nm GNP including the degradation factors due to beam attenuation. RESULTS: The greatest increase in DER compared to the standard 6.5 MV linac was for a 2.5 MV Be-target (factor of ∼ 2). Skin dose ranged from ∼ 10% (Be, 6.5 MV-80%) to ∼ 85% (Be, 2.5 MV-20%) depending on the target case. Attenuation of 2.5 MV beams at 22 cm was higher by ∼ 75% compared with the standard beam. Taking into account the attenuation at 22 cm depth, the effective dose enhancement was up to ∼ 60% above the DER of the high-Z target. For these cases the effective DER ranged between ∼ 1.6 and 6 compared with the standard linac. CONCLUSIONS: Low-Z (2.5 MV) GNPT is possible even after accounting for greater beam attenuation for deep-seated tumors (22 cm) and the increased skin dose. Further, it can lead to significant sparing of normal tissue while simultaneously escalating the dose in the tumor cells.

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator.

PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilovoltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data. METHODS: We have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multi-channel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm(2). The results were compared against Monte Carlo simulations. RESULTS: Dose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%-3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios. CONCLUSIONS: EBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated.

Beam quality and dose perturbation of 6 MV flattening-filter-free linac.

The aim of this study is twofold: (a) determination of the spectral differences for flattening-filter-free (FFF) versus standard (STD) linac under various clinical conditions, (b) based on an extensive list of clinically important beam configurations, identification of clinical scenarios that lead to higher macroscopic dose perturbations due to the presence of high-Z material. The focus is on dose enhancement due to contrast agents including high-Z elements such as gold or gadolinium. EGSnrc was used to simulate clinical beams under various irradiation conditions: open/IMRT/spit-IMRT fields, in/out-off-field areas, different depths and field sizes. Spectra were calculated and analyzed for about 80 beams and for a total of 480 regions. Quantitative differential effects in beam quality were characterized using energy-dependent and cumulative dose perturbation metrics. Analysis of the spectral database showed that even though the general trends for both linacs (FFF/STD) were the same, there were crucial differences. In general, the relative changes between different conditions were smaller for FFF spectra. This was because of the higher component of low-energy photons of the FFF linac, which already lead to higher dose enhancement than for the STD linac (photon energies were more "uniformly" distributed for FFF spectra and henceforth their perturbation resulted in lesser relative changes). For out-of-field FFF spectra and split-IMRT fields the strongest enhancement were observed (∼25 and ∼5 respectively). Different spectral scenarios lead to different dose enhancements, however, they scale with the higher effective-Z of the materials and were directly related to the lower range of the spectra (<200 keV).

A fast analytic dose calculation method for arc treatments for kilovoltage small animal irradiators.

Arc treatments require calculation of dose for collections of discrete gantry angles. The sampling of angles must balance between short computation time of small angle sets and the better calculation reliability of large sets. In this paper, an analytical formula is presented that allows calculation of dose delivered during continuous rotation of the gantry. The formula holds valid for continuous short arcs of up to about 30° and is derived by integrating a dose formula over gantry angles within a small angle approximation. Doses for longer arcs may be obtained in terms of doses for shorter arcs. The formula is derived with an empirical beam model in water and extended to inhomogeneous media. It is validated with experimental data obtained by applying arc treatment using kV small animal irradiator to a phantom of solid water and lung-equivalent material. The results are a promising step towards efficient 3D dose calculation and inverse planning purposes. In principle, this method also applies to VMAT dose calculation and optimization but requires extensions.