Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

PURPOSE: Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling. METHODS: A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor. RESULTS: The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively. CONCLUSION: Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

Mathematical solutions of the TG-43 geometry function for curved line, ring, disk, sphere, dome and annulus sources, and applications for quality assurance.

Analytic solutions for the TG-43 geometry function for curved line, ring, disk, sphere, dome and annulus shapes containing uniform distributions of air-kerma are derived. These geometry functions describe how dose distributions vary strictly due to source geometry and not including attenuation or scatter effects. This work extends the use of geometry functions for individual sources to applicators containing multiple sources. Such geometry functions may be used to verify dose distributions computed using advanced techniques, including QA of model-based dose calculation algorithms. The impact of source curvature on linear and planar implants is considered along with the specific clinical case of brachytherapy eye plaques. For eye plaques, the geometry function for a domed distribution is used with published Monte Carlo dose distributions to determine a radial dose function and anisotropy function which includes all the scatter and attenuation effects due to the phantom, eye plaque and sources. This TG-43 model of brachytherapy eye plaques exactly reproduces azimuthally averaged Monte Carlo calculations, both inside and outside the eye.

A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy.

Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

Calculation of beta-ray dose distributions from ophthalmic applicators and comparison with measurements in a model eye.

Dose distributions throughout the eye, from three types of beta-ray ophthalmic applicators, were calculated using the EGS4, ACCEPT 3.0, and other Monte Carlo codes. The applicators were those for which doses were measured in a recent international intercomparison [Med. Phys. 28, 1373 (2001)], planar applicators of 106Ru-106Rh and 90Sr-90Y and a concave 106Ru-106Rh applicator. The main purpose was to compare the results of the various codes with average experimental values. For the planar applicators, calculated and measured doses on the source axis agreed within the experimental errors (<10%) to a depth of 7 mm for 106Ru-106Rh and 5 mm for 90Sr-90Y. At greater distances the measured values are larger than those calculated. For the concave 106Ru-106Rh applicator, there was poor agreement among available calculations and only those calculated by ACCEPT 3.0 agreed with measured values. In the past, attempts have been made to derive such dose distributions simply, by integrating the appropriate point-source dose function over the source. Here, we investigated the accuracy of this procedure for encapsulated sources, by comparing such results with values calculated by Monte Carlo. An attempt was made to allow for the effects of the silver source window but no corrections were made for scattering from the source backing. In these circumstances, at 6 mm depth, the difference in the results of the two calculations was 14%-18% for a planar 106Ru-l06Rh applicator and up to 30% for the concave applicator. It becomes worse at greater depths. These errors are probably caused mainly by differences between the spectrum of beta particles transmitted by the silver window and those transmitted by a thickness of water having the same attenuation properties.

Probable risk of tumour induction after retro-orbital irradiation for Graves' ophthalmopathy.

Retrobulbar irradiation for Graves' ophthalmopathy is considered as a safe treatment and has recently been recommended as the initial treatment for patients with moderately severe eye problems. However, calculations using risk factors presently known reveal a theoretical risk of radiation-induced cancer of 1.2%. Therefore, the authors suggest that this treatment should be reserved for the elderly patient, for example above the age of 40-50 years.

Extrapolation chamber measurements of 90Sr + 90Y beta-particle ophthalmic applicator dose rates.

Aspects of extrapolation chamber dose-rate measurements of 90Sr + 90Y beta-particle ophthalmic applicators are examined in this report, including the proper choice of collector electrode size, the gap width over which the measurement should be done, the effect of the entrance window materials, and the stopping-power ratio. Experiments, a simple analytic model for the effect of chamber geometry and nonzero gap width, and more detailed Monte Carlo simulations were used. The variation of the planar flux density as a function of angle for a thick 90Sr + 90Y source was measured and used as input for the model. From Monte Carlo simulation, the dose rate for tissue irradiation falls off by 8% between the surface and a depth of 7 mg/cm2. The derivative of chamber ionization as a function of gap width, needed for the dose-rate calibration, increases rapidly as the gap width decreases, typically by a factor of about 2 between gap widths of 1.5 and 0.15 mm. About half of this change is due to ionizing electrons leaving the collection volume at the larger gap widths as shown by the analytic model; the rest of the change is due to ionizing electrons which backscatter from the collector electrode and its backing as shown by Monte Carlo simulations. The backscattering effect increases the derived surface dose by a factor of 1.46. A satisfactory dose-rate extrapolation is obtained from gap widths of 0.1-0.25 mm, where the total ionization current is observed to be nearly linear in gap width.