Preclinical Models of Anal Cancer Combined-Modality Therapy.

INTRODUCTION: There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer treatments. MATERIALS AND METHODS: Transgenic K14E6/E7 mice were treated with 7, 12-dimethylbenz(a)anthracene until anal tumors developed. Mice were treated with localized radiation in addition to chemotherapy (combined-modality therapy [CMT]) and compared to no treatment control (NTC). K14E6/E7 mouse anal spheroids with and without Pik3ca mutations were isolated and treated with vehicle, LY3023414 (LY3) (a drug previously shown to be effective in cancer prevention), CMT, or CMT + LY3. RESULTS: In the in vivo model, there was a significant increase in survival in the CMT group compared to the NTC group (P = 0.0392). In the ex vivo model, there was a significant decrease in the mean diameter of CMT and CMT + LY3-treated spheroids compared to vehicle (P ≤ 0.0001). For LY3 alone compared to vehicle, there was a statistically significant decrease in spheroid size in the K14E6/E7 group without mutation (P = 0.0004). CONCLUSIONS: We have provided proof of concept for two preclinical anal cancer treatment models that allow for the future testing of novel therapies for anal cancer.

Air-kerma strength determination of an HDR 192 Ir source including a geometric sensitivity study of the seven-distance method.

PURPOSE: To perform an in-air air-kerma strength (SK) calibration of the Bebig model Ir2.A85-2 192Ir high-dose rate (HDR) brachytherapy source manufactured by Mallinckrodt Medical (Westerduinweg, Germany) with the NIST-traceable seven-distance technique established by the University of Wisconsin. A comparison was made between the reference air-kerma rate (RAKR) reported on a certificate from the Physikalisch-Technische Bundesanstalt (Berlin, Germany) (PTB) primary laboratory and the SK determined at the University of Wisconsin Madison Radiation Research Center (UWMRRC). A theoretical sensitivity study was performed to investigate the impact that variations in the experimental setup have on the computed SK from the seven-distance algorithm in order to determine if the uncertainty budget for the seven-distance method should be expanded. METHODS: The manufacturer-reported SK for the source was compared to the SK determined from the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) transfer standard well chambers and the seven-distance technique. Monte Carlo techniques (MCNP6) were employed to compare the theoretical SK calibration coefficients of a Standard Imaging (Middleton, WI) HDR1000 Plus well chamber using Standard Imaging model 70010 and model 70110 source holders to determine if a holder dependence was present. Radiochromic film (EBT3, Ashland) exposures were performed to assess the dose distribution of the source in phantom. The seven-distance algorithm was coded in MATLAB®(R2013b) and benchmarked with MCNP6 with the capacity to model distance offset behaviors among nominal positions. This offset model was used in a Monte Carlo simulation coded in MATLAB to determine the average uncertainty in the SK calculations from the seven-distance algorithm. RESULTS: The measured SK using the seven-distance technique at the UWMRRC agreed with the RAKR reported on the PTB source certificate and the SK on the Mallinckrodt source certificate to within 0.28% and -0.79%, respectively. It was found that the difference between the SK measured from the transfer standard well chambers at the UWADCL and the seven-distance method was between 0.13% and 0.30% at the 95% confidence level. Monte Carlo results showed negligible differences between the simulated SK calibration coefficient for an HDR1000 Plus well chamber using the model 70010 or model 70110 source holder. The autoradiographs from the source in Virtual WaterTM showed that the dose distribution is symmetric. Additionally, the sensitivity study performed in MATLAB showed that the SK calculated with the seven-distance algorithm could deviate by 0.24% from randomly generated distance offsets within 1mm in magnitude. CONCLUSION: The differences between the SK measurements determined from the seven-distance technique and the accredited UWADCL measurement results were within the k = 2 uncertainty reported for an accredited calibration. Excellent agreement was found between the measured SK and RAKR methods used at the UWMRRC and PTB, respectively. Additionally, the sensitivity study has shown that the seven-distance algorithm accurately determines the SK of a source while having a variable chamber offset among nominal positions; the uncertainty budget for the seven-distance method does not need to be expanded at this time. It has been determined that the current standard used by the UWADCL for well chamber calibrations is valid for the Bebig model Ir2.A85-2 192Ir brachytherapy source.

Reply to: Comment on: polarity effects and apparent ion recombination in microionization chambers [Med. Phys. 43(5) 2141-2152 (2016)].

We would like to thank Dr. Brivio et al. [Med. Phys.] for their comment on our recent paper. Miller et al. [Med. Phys. 43 (2016) 2141-2152] determined the primary cause of voltage-dependent polarity effects in microchambers to be a potential difference between the guard and collecting electrodes. In their comment, Brivio et al., offer an explanation for the cause of such potential differences. Brivio et al. attribute the potential difference to the disparity in the work functions between guard and collecting electrodes composed of different materials. However, all of the microchambers investigated in Miller et al. contained a guard and collecting electrode which were composed of the same material. Therefore, the explanation offered by Brivio et al. that "the electric potential perturbation arises from the work function difference of the disparate materials electrodes" does not explain the polarity effects exhibited by the microchambers investigated in Miller et al., all of which contain electrodes composed of the same materials.

Ion recombination and polarity corrections for small-volume ionization chambers in high-dose-rate, flattening-filter-free pulsed photon beams.

PURPOSE: To investigate ion recombination and polarity effects in scanning and microionization chambers when used with digital electrometers and high-dose-rate linac beams such as flattening-filter-free (FFF) fields, and to compare results against conventional pulsed and continuous photon beams. METHODS: Saturation curves were obtained for one Farmer-type ionization chamber and eight small-volume chamber models with volumes ranging from 0.01 to 0.13 cm3 using a Varian TrueBeam™ STx with FFF capability. Three beam modes (6 MV, 6 MV FFF, and 10 MV FFF) were investigated, with nominal dose-per-pulse values of 0.0278, 0.0648, and 0.111 cGy/pulse, respectively, at dmax . Saturation curves obtained using the Theratronics T1000 60 Co unit at the UWADCL and a conventional linear accelerator (Varian Clinac iX) were used to establish baseline behavior. Jaffé plots were fitted to obtain Pion , accounting for exponential effects such as charge multiplication. These values were compared with the two-voltage technique recommended in TG-51, and were plotted as a function of dose-per-pulse to assess the ability of small-volume chambers to meet reference-class criteria in FFF beams. RESULTS: Jaffé- and two-voltage-determined Pion values measured for high-dose-rate beams agreed within 0.1% for the Farmer-type chamber and 1% for scanning and microionization chambers, with the exception of the CC01 which agreed within 2%. With respect to ion recombination and polarity effects, the Farmer-type chamber, scanning chambers and the Exradin A26 microchamber exhibited reference-class behavior in all beams investigated, with the exception of the IBA CC04 scanning chamber, which had an initial recombination correction that varied by 0.2% with polarity. All microchambers investigated, with the exception of the A26, exhibited anomalous polarity and ion recombination behaviors that make them unsuitable for reference dosimetry in conventional and high-dose-rate photon beams. CONCLUSIONS: The results of this work demonstrate that recombination and polarity behaviors seen in conventional pulsed and continuous photon beams trend accordingly in high-dose-rate FFF linac beams. Several models of small-volume ionization chambers used with a digital electrometer have been shown to meet reference-class requirements with respect to ion recombination and polarity, even in the high-dose-rate environment. For such chambers, a two-voltage technique agreed well with more rigorous methods of determining Pion . However, the results emphasize the need for careful reference detector selection, and indicate that ionization chambers ought to be extensively tested in each beam of interest prior to their use for reference dosimetry.

Polarity effects and apparent ion recombination in microionization chambers.

PURPOSE: Microchambers demonstrate anomalous voltage-dependent polarity effects. Existing polarity and ion recombination correction factors do not account for these effects. As a result, many commercial microchamber models do not meet the specification of a reference-class ionization chamber as defined by the American Association of Physicists in Medicine. The purpose of this investigation is to determine the cause of these voltage-dependent polarity effects. METHODS: A series of microchamber prototypes were produced to isolate the source of the voltage-dependent polarity effects. Parameters including ionization-chamber collecting-volume size, stem and cable irradiation, chamber assembly, contaminants, high-Z materials, and individual chamber components were investigated. Measurements were performed with electrodes coated with graphite to isolate electrode conductivity. Chamber response was measured as the potential bias of the guard electrode was altered with respect to the collecting electrode, through the integration of additional power supplies. Ionization chamber models were also simulated using comsol Multiphysics software to investigate the effect of a potential difference between electrodes on electric field lines and collecting volume definition. RESULTS: Investigations with microchamber prototypes demonstrated that the significant source of the voltage-dependent polarity effects was a potential difference between the guard and collecting electrodes of the chambers. The voltage-dependent polarity effects for each prototype were primarily isolated to either the guard or collecting electrode. Polarity effects were reduced by coating the isolated electrode with a conductive layer of graphite. Polarity effects were increased by introducing a potential difference between the electrodes. comsol simulations further demonstrated that for a given potential difference between electrodes, the collecting volume of the chamber changed as the applied voltage was altered, producing voltage-dependent polarity effects in the chamber response. Ionization chamber measurements and comsol simulations demonstrated an inverse relationship between the chamber collecting volume size and the severity of voltage-dependent polarity effects on chamber response. The effect of a given potential difference on chamber polarity effects was roughly ten times greater for microchambers as compared to Farmer-type chambers. Stem and cable irradiations, chamber assembly, contaminants, and high-Z materials were not found to be a significant source of the voltage-dependent polarity effects. CONCLUSIONS: A potential difference between the guard and collecting electrodes was found to be the primary source of the voltage-dependent polarity effects demonstrated by microchambers. For a given potential difference between electrodes, the relative change in the collecting volume is smaller for larger-volume chambers, illustrating why these polarity effects are not seen in larger-volume chambers with similar guard and collecting electrode designs. Thus, for small-volume chambers, it is necessary to reduce the potential difference between the guard and collecting electrodes in order to reduce polarity effects for reference dosimetry measurements.

Development of a phantom to validate high-dose-rate brachytherapy treatment planning systems with heterogeneous algorithms.

PURPOSE: This work presents the development of a phantom to verify the treatment planning system (TPS) algorithms used for high-dose-rate (HDR) brachytherapy. It is designed to measure the relative dose in a heterogeneous media. The experimental details used, simulation methods, and comparisons with a commercial TPS are also provided. METHODS: To simulate heterogeneous conditions, four materials were used: Virtual Water™ (VM), BR50/50™, cork, and aluminum. The materials were arranged in 11 heterogeneity configurations. Three dosimeters were used to measure the relative response from a HDR (192)Ir source: TLD-100™, Gafchromic(®) EBT3 film, and an Exradin™ A1SL ionization chamber. To compare the results from the experimental measurements, the various configurations were modeled in the penelope/penEasy Monte Carlo code. Images of each setup geometry were acquired from a CT scanner and imported into BrachyVision™ TPS software, which includes a grid-based Boltzmann solver Acuros™. The results of the measurements performed in the heterogeneous setups were normalized to the dose values measured in the homogeneous Virtual Water™ setup and the respective differences due to the heterogeneities were considered. Additionally, dose values calculated based on the American Association of Physicists in Medicine-Task Group 43 formalism were compared to dose values calculated with the Acuros™ algorithm in the phantom. Calculated doses were compared at the same points, where measurements have been performed. RESULTS: Differences in the relative response as high as 11.5% were found from the homogeneous setup when the heterogeneous materials were inserted into the experimental phantom. The aluminum and cork materials produced larger differences than the plastic materials, with the BR50/50™ material producing results similar to the Virtual Water™ results. Our experimental methods agree with the penelope/penEasy simulations for most setups and dosimeters. The TPS relative differences with the Acuros™ algorithm were similar in both experimental and simulated setups. The discrepancy between the BrachyVision™, Acuros™, and TG-43 dose responses in the phantom described by this work exceeded 12% for certain setups. CONCLUSIONS: The results derived from the phantom measurements show good agreement with the simulations and TPS calculations, using Acuros™ algorithm. Differences in the dose responses were evident in the experimental results when heterogeneous materials were introduced. These measurements prove the usefulness of the heterogeneous phantom for verification of HDR treatment planning systems based on model-based dose calculation algorithms.

A modified dose calculation formalism for electronic brachytherapy sources.

PURPOSE: To propose a modification of the current dose calculation formalism introduced in the Task Group No. 43 Report (TG-43) to accommodate an air-kerma rate standard for electronic brachytherapy sources as an alternative to an air-kerma strength standard. METHODS: Electronic brachytherapy sources are miniature x-ray tubes emitting low energies with high-dose-rates. The National Institute of Standards and Technology (NIST) has introduced a new primary air-kerma rate standard for one of these sources, in contrast to air-kerma strength. A modification of the TG-43 protocol for calculation of dose-rate distributions around electronic brachytherapy sources including sources in an applicator is presented. It cannot be assumed that the perturbations from sources in an applicator are negligible, and thus, the applicator is incorporated in the formalism. The modified protocol mimics the fundamental methodology of the original TG-43 formalism, but now incorporates the new NIST-traceable source strength metric of air-kerma rate at 50 cm and introduces a new subscript, i, to denote the presence of an applicator used in treatment delivery. Applications of electronic brachytherapy sources for surface brachytherapy are not addressed in this Technical Note since they are well documented in other publications. RESULTS: A modification of the AAPM TG-43 protocol has been developed to accommodate an air-kerma rate standard for electronic brachytherapy sources as an alternative to an air-kerma strength standard. CONCLUSIONS: The modified TG-43 formalism allows dose calculations to be performed using a new NIST-traceable source strength metric and introduces the concept of applicator-specific formalism parameters denoted with subscript, i.

Experimental and Monte Carlo dosimetric characterization of a 1 cm (103)Pd brachytherapy source.

PURPOSE: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of a new elongated (103)Pd brachytherapy source through both experimental measurements and Monte Carlo (MC) simulations. Measured and MC-calculated dose distributions were used to determine the American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters for this source. METHODS AND MATERIALS: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and was simulated with the MCNP5 radiation transport code. Measured and MC results were normalized to their respective mean values and then compared. The source dose distribution was determined from measurements with LiF:Mg,Ti thermoluminescent dosimeter (TLD) microcubes and MC simulations. TG-43 dosimetry parameters for the source, including the dose-rate constant, Λ, two-dimensional anisotropy function, F(r, θ), and line-source radial dose function, gL(r), were determined from the TLD measurements and MC simulations. RESULTS: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy of the source showed that ≥95% of the normalized values for each source were within 1.2% of the mean value. TLD measurements and MC simulations of Λ, F(r, θ), and gL(r) agreed to within the associated uncertainties. CONCLUSIONS: This new (103)Pd source exhibits a high level of azimuthal symmetry as indicated by the measured and MC-calculated results for the in-air azimuthal anisotropy. TG-43 dosimetry parameters for the source were determined through TLD measurements and MC simulations.

Development and characterization of a three-dimensional radiochromic film stack dosimeter for megavoltage photon beam dosimetry.

PURPOSE: Three-dimensional (3D) dosimeters are particularly useful for verifying the commissioning of treatment planning and delivery systems, especially with the ever-increasing implementation of complex and conformal radiotherapy techniques such as volumetric modulated arc therapy. However, currently available 3D dosimeters require extensive experience to prepare and analyze, and are subject to large measurement uncertainties. This work aims to provide a more readily implementable 3D dosimeter with the development and characterization of a radiochromic film stack dosimeter for megavoltage photon beam dosimetry. METHODS: A film stack dosimeter was developed using Gafchromic(®) EBT2 films. The dosimeter consists of 22 films separated by 1 mm-thick spacers. A Virtual Water™ phantom was created that maintains the radial film alignment within a maximum uncertainty of 0.3 mm. The film stack dosimeter was characterized using simulations and measurements of 6 MV fields. The absorbed-dose energy dependence and orientation dependence of the film stack dosimeter were investigated using Monte Carlo simulations. The water equivalence of the dosimeter was determined by comparing percentage-depth-dose (PDD) profiles measured with the film stack dosimeter and simulated using Monte Carlo methods. Film stack dosimeter measurements were verified with thermoluminescent dosimeter (TLD) microcube measurements. The film stack dosimeter was also used to verify the delivery of an intensity-modulated radiation therapy (IMRT) procedure. RESULTS: The absorbed-dose energy response of EBT2 film differs less than 1.5% between the calibration and film stack dosimeter geometries for a 6 MV spectrum. Over a series of beam angles ranging from normal incidence to parallel incidence, the overall variation in the response of the film stack dosimeter is within a range of 2.5%. Relative to the response to a normally incident beam, the film stack dosimeter exhibits a 1% under-response when the beam axis is parallel to the film planes. Measured and simulated PDD profiles agree within a root-mean-square difference of 1.3%. In-field film stack dosimeter and TLD measurements agree within 5%, and measurements in the field penumbra agree within 0.5 mm. Film stack dosimeter and TLD measurements have expanded (k = 2) overall measurement uncertainties of 6.2% and 5.8%, respectively. Film stack dosimeter measurements of an IMRT dose distribution have 98% agreement with the treatment planning system dose calculation, using gamma criteria of 3% and 2 mm. CONCLUSIONS: The film stack dosimeter is capable of high-resolution, low-uncertainty 3D dose measurements, and can be readily incorporated into an existing film dosimetry program.

A novel high-throughput irradiator for in vitro radiation sensitivity bioassays.

This paper describes the development and characterization of a fully automated in vitro cell irradiator using an electronic brachytherapy source to perform radiation sensitivity bioassays. This novel irradiator allows complex variable dose and dose rate schemes to be delivered to multiple wells of 96-well culture plates used in standard biological assays. The Xoft Axxent® eBx™ was chosen as the x-ray source due to its ability to vary tube current up to 300 µA for a 50 kVp spectrum using clinical surface applicators. Translation of the multiwell plate across the fixed radiation field is achieved using a precision motor driven computer controlled positioning system. A series of measurements was performed to characterize dosimetric performance of the system. Measurements have shown that the radiation output measured with an end window ionization chamber is stable between operating currents of 50-300 µA. In addition, radiochromic film was used to characterize the field flatness and symmetry. The average field flatness in the in-plane and cross-plane direction was 2.9 ± 1.0% and 4.0 ± 1.7%, respectively. The average symmetry in the in-plane and cross-plane direction was 1.8 ± 0.9% and 1.6 ± 0.5%, respectively. The optimal focal spot resolution at the cellular plane was determined by measuring sequential irradiations on radiochromic film for three different well spacing schemes. It was determined that the current system can irradiate every other well with negligible impact on the radiation field characteristics. Finally, a performance comparison between this system and a common cabinet irradiator is presented.

Dosimetric characterization and output verification for conical brachytherapy surface applicators. Part I. Electronic brachytherapy source.

PURPOSE: Historically, treatment of malignant surface lesions has been achieved with linear accelerator based electron beams or superficial x-ray beams. Recent developments in the field of brachytherapy now allow for the treatment of surface lesions with specialized conical applicators placed directly on the lesion. Applicators are available for use with high dose rate (HDR)(192)Ir sources, as well as electronic brachytherapy sources. Part I of this paper will discuss the applicators used with electronic brachytherapy sources; Part II will discuss those used with HDR (192)Ir sources. Although the use of these applicators has gained in popularity, the dosimetric characteristics including depth dose and surface dose distributions have not been independently verified. Additionally, there is no recognized method of output verification for quality assurance procedures with applicators like these. Existing dosimetry protocols available from the AAPM bookend the cross-over characteristics of a traditional brachytherapy source (as described by Task Group 43) being implemented as a low-energy superficial x-ray beam (as described by Task Group 61) as observed with the surface applicators of interest. METHODS: This work aims to create a cohesive method of output verification that can be used to determine the dose at the treatment surface as part of a quality assurance/commissioning process for surface applicators used with HDR electronic brachytherapy sources (Part I) and(192)Ir sources (Part II). Air-kerma rate measurements for the electronic brachytherapy sources were completed with an Attix Free-Air Chamber, as well as several models of small-volume ionization chambers to obtain an air-kerma rate at the treatment surface for each applicator. Correction factors were calculated using MCNP5 and EGSnrc Monte Carlo codes in order to determine an applicator-specific absorbed dose to water at the treatment surface from the measured air-kerma rate. Additionally, relative dose measurements of the surface dose distributions and characteristic depth dose curves were completed in-phantom. RESULTS: Theoretical dose distributions and depth dose curves were generated for each applicator and agreed well with the measured values. A method of output verification was created that allows users to determine the applicator-specific dose to water at the treatment surface based on a measured air-kerma rate. CONCLUSIONS: The novel output verification methods described in this work will reduce uncertainties in dose delivery for treatments with these kinds of surface applicators, ultimately improving patient care.

Dosimetric characterization and output verification for conical brachytherapy surface applicators. Part II. High dose rate 192Ir sources.

PURPOSE: Historically, treatment of malignant surface lesions has been achieved with linear accelerator based electron beams or superficial x-ray beams. Recent developments in the field of brachytherapy now allow for the treatment of surface lesions with specialized conical applicators placed directly on the lesion. Applicators are available for use with high dose rate (HDR)(192)Ir sources, as well as electronic brachytherapy sources. Part I of this paper discussed the applicators used with electronic brachytherapy sources. Part II will discuss those used with HDR (192)Ir sources. Although the use of these applicators has gained in popularity, the dosimetric characteristics have not been independently verified. Additionally, there is no recognized method of output verification for quality assurance procedures with applicators like these. METHODS: This work aims to create a cohesive method of output verification that can be used to determine the dose at the treatment surface as part of a quality assurance/commissioning process for surface applicators used with HDR electronic brachytherapy sources (Part I) and(192)Ir sources (Part II). Air-kerma rate measurements for the (192)Ir sources were completed with several models of small-volume ionization chambers to obtain an air-kerma rate at the treatment surface for each applicator. Correction factors were calculated using MCNP5 and EGSnrc Monte Carlo codes in order to determine an applicator-specific absorbed dose to water at the treatment surface from the measured air-kerma rate. Additionally, relative dose measurements of the surface dose distributions and characteristic depth dose curves were completed in-phantom. RESULTS: Theoretical dose distributions and depth dose curves were generated for each applicator and agreed well with the measured values. A method of output verification was created that allows users to determine the applicator-specific dose to water at the treatment surface based on a measured air-kerma rate. CONCLUSIONS: The novel output verification methods described in this work will reduce uncertainties in dose delivery for treatments with these kinds of surface applicators, ultimately improving patient care.

Comparison of air-kerma strength determinations for HDR (192)Ir sources.

PURPOSE: To perform a comparison of the interim air-kerma strength standard for high dose rate (HDR) (192)Ir brachytherapy sources maintained by the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) with measurements of the various source models using modified techniques from the literature. The current interim standard was established by Goetsch et al. in 1991 and has remained unchanged to date. METHODS: The improved, laser-aligned seven-distance apparatus of the University of Wisconsin Medical Radiation Research Center (UWMRRC) was used to perform air-kerma strength measurements of five different HDR (192)Ir source models. The results of these measurements were compared with those from well chambers traceable to the original standard. Alternative methodologies for interpolating the (192)Ir air-kerma calibration coefficient from the NIST air-kerma standards at (137)Cs and 250 kVp x rays (M250) were investigated and intercompared. As part of the interpolation method comparison, the Monte Carlo code EGSnrc was used to calculate updated values of A(wall) for the Exradin A3 chamber used for air-kerma strength measurements. The effects of air attenuation and scatter, room scatter, as well as the solution method were investigated in detail. RESULTS: The average measurements when using the inverse N(K) interpolation method for the Classic Nucletron, Nucletron microSelectron, VariSource VS2000, GammaMed Plus, and Flexisource were found to be 0.47%, -0.10%, -1.13%, -0.20%, and 0.89% different than the existing standard, respectively. A further investigation of the differences observed between the sources was performed using MCNP5 Monte Carlo simulations of each source model inside a full model of an HDR 1000 Plus well chamber. CONCLUSIONS: Although the differences between the source models were found to be statistically significant, the equally weighted average difference between the seven-distance measurements and the well chambers was 0.01%, confirming that it is not necessary to update the current standard maintained at the UWADCL.

Characterizing the marker-dye correction for Gafchromic(®) EBT2 film: a comparison of three analysis methods.

PURPOSE: Gafchromic(®) EBT2 film has a yellow marker dye incorporated into the active layer of the film that can be used to correct the film response for small variations in thickness. This work characterizes the effect of the marker-dye correction on the uniformity and uncertainty of dose measurements with EBT2 film. The effect of variations in time postexposure on the uniformity of EBT2 is also investigated. METHODS: EBT2 films were used to measure the flatness of a (60)Co field to provide a high-spatial resolution evaluation of the film uniformity. As a reference, the flatness of the (60)Co field was also measured with Kodak EDR2 films. The EBT2 films were digitized with a flatbed document scanner 24, 48, and 72 h postexposure, and the images were analyzed using three methods: (1) the manufacturer-recommended marker-dye correction, (2) an in-house marker-dye correction, and (3) a net optical density (OD) measurement in the red color channel. The field flatness was calculated from orthogonal profiles through the center of the field using each analysis method, and the results were compared with the EDR2 measurements. Uncertainty was propagated through a dose calculation for each analysis method. The change in the measured field flatness for increasing times postexposure was also determined. RESULTS: Both marker-dye correction methods improved the field flatness measured with EBT2 film relative to the net OD method, with a maximum improvement of 1% using the manufacturer-recommended correction. However, the manufacturer-recommended correction also resulted in a dose uncertainty an order of magnitude greater than the other two methods. The in-house marker-dye correction lowered the dose uncertainty relative to the net OD method. The measured field flatness did not exhibit any unidirectional change with increasing time postexposure and showed a maximum change of 0.3%. CONCLUSIONS: The marker dye in EBT2 can be used to improve the response uniformity of the film. Depending on the film analysis method used, however, application of a marker-dye correction can improve or degrade the dose uncertainty relative to the net OD method. The uniformity of EBT2 was found to be independent of the time postexposure.

Determination of exit skin dose for 192Ir intracavitary accelerated partial breast irradiation with thermoluminescent dosimeters.

PURPOSE: Intracavitary accelerated partial breast irradiation (APBI) has become a popular treatment for early stage breast cancer in recent years due to its shortened course of treatment and simplified treatment planning compared to traditional external beam breast conservation therapy. However, the exit dose to the skin is a major concern and can be a limiting factor for these treatments. Most treatment planning systems (TPSs) currently used for high dose-rate (HDR) 192Ir brachytherapy overestimate the exit skin dose because they assume a homogeneous water medium and do not account for finite patient dimensions. The purpose of this work was to quantify the TPS overestimation of the exit skin dose for a group of patients and several phantom configurations. METHODS: The TPS calculated skin dose for 59 HDR 192Ir APBI patients was compared to the skin dose measured with LiF:Mg,Ti thermoluminescent dosimeters (TLDs). Additionally, the TPS calculated dose was compared to the TLD measured dose and the Monte Carlo (MC) calculated dose for eight phantom configurations. Four of the phantom configurations simulated treatment conditions with no scattering material beyond the point of measurement and the other four configurations simulated the homogeneous scattering conditions assumed by the TPS. Since the calibration TLDs for this work were irradiated with 137Cs and the experimental irradiations were performed with 192Ir, experiments were performed to determine the intrinsic energy dependence of the TLDs. Correction factors that relate the dose at the point of measurement (center of TLD) to the dose at the point of interest (basal skin layer) were also determined and applied for each irradiation geometry. RESULTS: The TLD intrinsic energy dependence for 192Ir relative to 137Cs was 1.041 +/- 1.78%. The TPS overestimated the exit skin dose by an average of 16% for the group of 59 patients studied, and by 9%-15% for the four phantom setups simulating treatment conditions. For the four phantom setups simulating the conditions assumed by the TPS, the TPS calculated dose agreed well with the TLD and MC results (within 3% and 1%, respectively). The inverse square geometry correction factor ranged from 1.023 to 1.042, and an additional correction factor of 0.978 was applied to account for the lack of charged particle equilibrium in the TLD and basal skin layer. CONCLUSIONS: TPS calculations that assume a homogeneous water medium overestimate the exit skin dose for intracavitary APBI treatments. It is important to determine the actual skin dose received during intracavitary APBI to determine the skin dose-response relationship and establish dose limits for optimal skin sparing. This study has demonstrated that TLDs can measure the skin dose with an expanded uncertainty (k = 2) of 5.6% when the proper corrections are applied.

Investigation of a 90Sr/90Y source for intra-ocular treatment of wet age-related macular degeneration.

PURPOSE: The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long 90Sr/90Y source designed for treating wet age-related macular degeneration. METHODS: As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model. RESULTS: Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was +/-0.3%, with a maximum observed range of less than +/-0.5%. Clinical cannulae in the collimating insert showed an average of 17.8% +/-0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude difference of approximately 0.1% of the reference signal. CONCLUSIONS: This investigation confirms that the signal for an acceptably deployed source in the collimating insert is between 17.5% and 21.5% of the reference signal, as calculated using Monte Carlo models. Clinical cannulae for which the source deployment verification measurement falls outside the acceptable range should not be used to treat patients.

Ophthalmic applicators: an overview of calibrations following the change to SI units.

Since the NIST dose to water standard for 90Sr/90Y ophthalmic applicators was introduced, numerous sources have undergone calibration either at NIST or at the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL). From 1997 to 2008, 222 of these beta-emitting sources were calibrated at the UWADCL, and prior reference source strength values were available for 149 of these sources. A survey of UWADCL ophthalmic applicator calibrations is presented here, demonstrating an average discrepancy of -19% with a standard deviation of +/- 16% between prior reference values and the NIST-traceable UWADCL absorbed dose to water calibrations. Values ranged from -49% to +42%.

Primary calibration of coiled 103Pd brachytherapy sources.

Coiled 103Pd brachytherapy sources have been developed by RadioMed Corporation for use as low-dose-rate (LDR) interstitial implants. The coiled sources are provided in integer lengths from 1 to 6 cm and address many common issues seen with traditional LDR brachytherapy sources. The current standard for determining the air-kerma strength (SK) of low-energy LDR brachytherapy sources is the National Institute of Standards and Technology's Wide-Angle Free-Air Chamber (NIST WAFAC). Due to geometric limitations, however, the NIST WAFAC is unable to determine the S(K) of sources longer than 1 cm. This project utilized the University of Wisconsin's Variable-Aperture Free-Air Chamber (UW VAFAC) to determine the S(K) of the longer coiled sources. The UW VAFAC has shown agreement in S(K) values of 1 cm length coils to within 1% of those determined with the NIST WAFAC, but the UW VAFAC does not share the same geometric limitations as the NIST WAFAC. A new source holder was constructed to hold the coiled sources in place during measurements with the UW VAFAC. Correction factors for the increased length of the sources have been determined and applied to the measurements. Using the new source holder and corrections, the S(K) of 3 and 6 cm coiled sources has been determined. Corrected UW VAFAC data and ionization current measurements from well chambers have been used to determine calibration coefficients for use in the measurement of 3 and 6 cm coiled sources in well chambers. Thus, the UW VAFAC has provided the first transferable, primary measurement of low-energy LDR brachytherapy sources with lengths greater than 1 cm.

Response of an implantable MOSFET dosimeter to 192Ir HDR radiation.

New in vivo dosimetry methods would be useful for clinical HDR brachytherapy. An implantable MOSFET Dose Verification System designed by Sicel Technologies, Inc. was examined for use with 192Ir HDR applications. This investigation demonstrated that varying the dose rate from 22 to 84 cGy/min did not change detector response. The detectors exhibited a higher sensitivity to 192Ir energies than 60Co energies. A nonlinear accumulated dose effect was characterized by three third-order polynomials fit to data from detectors placed at three different distances from the source. The detectors were found to have minimal rotational angular dependence. A strong longitudinal angular dependence was found when the detector's copper coil and electronics assembly were aligned between the MOSFETs and incident radiation. This orientation showed a 16% decrease in response relative to other orientations tested.

Monte Carlo aided design of an improved well-type ionization chamber for low energy brachytherapy sources.

The determination of the air kerma strength of a brachytherapy seed is necessary for effective treatment planning. Well-type ionization chambers are used on site at therapy clinics to determine the air kerma strength of seeds. In this work, an improved well-type ionization chamber for low energy, low dose rate brachytherapy sources is designed using Monte Carlo transport calculations to aid in the design process. The design improvements are the elimination of the air density induced over-response effect seen in other air-communicating chambers for low energy photon sources, and a larger signal strength (response or current) for 103Pd and 125I based seeds. A prototype well chamber based on the Monte Carlo aided design but using graphite coated acrylic walls rather than the design basis air equivalent plastic (C-552) walls was constructed and experimentally evaluated. The prototype chamber produced an 85% stronger signal when measuring a commonly used 103Pd seed and a 26% stronger signal when measuring a commonly used 125I seed when compared to another commonly used well chamber. The normalized PTP corrected chamber response is, at most, 1.3% and 2.4% over unity for air densities/pressures corresponding to an elevation of 3048 m (10000 feet) above sea level for the commonly used 103Pd and 125I based seeds respectively. Comparing calculated and measured chamber responses for common 103Pd and 125I based brachytherapy seeds show agreement within 0.6% and 0.2%, respectively. We conclude that Monte Carlo transport calculations accurately model the response of this new well chamber and in general can be used to predict the response of well chambers. The prototype chamber built in this work responds as predicted by the Monte Carlo calculations.