Physical wedge as a tool for radiochromic film calibration.

Reliable calibration is one of the major challenges in using radiochromic films (RCF) for radiation dosimetry. In this study the feasibility of using dose gradients produced by a physical wedge (PW) for RCF calibration was investigated. The aim was to establish an efficient and reproducible method for calibrating RCF using a PW. Film strips were used to capture the wedge dose profile for five different exposures and the acquired scans were processed to generate corresponding net optical density wedge profiles. The proposed method was compared to the benchmark calibration, following the guidelines for precise calibration using uniform dose fields. The results of the benchmark comparison presented in this paper showed that using a single film strip for measuring wedge dose profile is sufficient for estimating a reliable calibration curve within the recorded dose range. Furthermore, the PW calibration can be extrapolated or extended by using multiple gradients for the optimal coverage of the desired calibration dose range. The method outlined in this paper can be readily replicated using the equipment and expertise commonly found in a radiotherapy center. Once the dose profile and central axis attenuation coefficient of the PW are determined, they can serve as a reference for a variety of calibrations using different types and batches of film. This investigation demonstrated that the calibration curves obtained with the presented PW calibration method are within the bounds of the measurement uncertainty evaluated for the conventional uniform dose field calibration method.

Evaluation of thoracic surface motion during the free breathing and deep inspiration breath hold methods.

The aim of this study was to evaluate thoracic surface motion from chest wall expansion during free breathing (FB) and deep inspiration breath hold (DIBH) methods, measured with and without 4-dimensional computed tomography (4D-CT) simulation, using equipment developed in-house. The respiratory amplitude and chest wall expansion were evaluated at 5 levels of the thorax, (the sterno-clavicular joint (SCJ), the second level, the intermammary line (IML), the fourth level and the caudal end of the xiphoid process (XP)) using radiopaque wires and potentiometers, with a CT scan simultaneously. This study included 25 examinees (10 volunteers performed FB, 10 volunteers performed DIBH and 5 patients performed FB). For low and irregular respiration, coaching was used, and its impact was evaluated for both breathing methods, FB and DIBH. The breathing amplitude performed with FB between volunteers and patients was not detectable at the SCJ; increasing to the abdomen, 3 mm vs 2 mm (p = 0.326) at the second level; 6 mm vs 4 mm (p = 0.042) at the IML; 10 mm vs 8 mm (p < 0.01) at the fourth level; and 23 mm vs 19 mm (p < 0.001) at the XP. Contrary to the DIBH, where breathing amplitude was greater at 2 first levels 18 mm (SCJ) and 20 mm (second level), decreasing to the abdomen, 14 mm (IML); 11 mm (fourth level); and 10 mm (XP). Chest wall expansion was not detected at the SCJ, while at other levels measured from 1 to 7 mm. Coaching was improve breathing amplitude, for both methods, FB (3 mm) and DIBH (5 mm). The location of amplification is different depending on the breathing method and the in-house phantom was useful to check the amplification level.

Energy dependence and dose response of Gafchromic EBT2 film over a wide range of photon, electron, and proton beam energies.

PURPOSE: Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characterization, especially energy dependence, has become critically important. The energy dependence of the dose response of Gafchromic EBT2 film is evaluated for a broad range of energies from different radiation sources used in radiation therapy. METHODS: The beams used for this study comprised of kilovoltage x rays (75, 125, and 250 kVp), 137Cs gamma (662 KeV), 60Co gamma (1.17-1.33 MeV), megavoltage x rays (6 and 18 MV), electron beams (6 and 20 MeV), and proton beams (100 and 250 MeV). The film's response to each of the above energies was measured over the dose range of 0.4-10 Gy, which corresponds to optical densities ranging from 0.05 to 0.74 for the film reader used. RESULTS: The energy dependence of EBT2 was found to be relatively small within measurement uncertainties (1 sigma = +/- 4.5%) for all energies and modalities. CONCLUSION: For relative and absolute dosimetry of radiation therapy beams, the weak energy dependence of the EBT2 makes it most suitable for clinical use compared to other films.

Validation of calculations for electrons modulated with conventional photon multileaf collimators.

Treating shallow tumors with a homogeneous dose while simultaneously minimizing the dose to distal critical organs remains a challenge in radiotherapy. One promising approach is modulated electron radiotherapy (MERT). Due to the scattering properties of electron beams, the commercially provided secondary and tertiary photon collimation systems are not conducive for electron beam delivery when standard source-to-surface distances are used. Also, commercial treatment planning systems may not accurately model electron-beam dose distributions when collimated without the standard applicators. However, by using the photon multileaf collimators (MLCs) to create segments to modulate electron beams, the quality of superficial tumor dose distributions may improve substantially. The purpose of this study is to develop and evaluate calculations for the narrow segments needed to modulate megavoltage electron beams using photon beam multileaf collimators. Modulated electron radiotherapy (MERT) will be performed with a conventional linear accelerator equipped with a 120 leaf MLC for 6-20 MeV electron beam energies. To provide a sharp penumbra, segments were delivered with short SSDs (70-85 cm). Segment widths (SW) ranging from 1 to 10 cm were configured for delivery and planning, using BEAMnrc Monte Carlo (MC) code, and the DOSXYZnrc MC dose calculations. Calculations were performed with voxel size of 0.2 x 0.2 x 0.1 cm3. Dosimetry validation was performed using radiographic film and micro- or parallel-plate chambers. Calculated and measured data were compared using technical computing software. Beam sharpness (penumbra) degraded with decreasing incident beam energy and field size (FS), and increasing SSD. A 70 cm SSD was found to be optimal. The PDD decreased significantly with decreasing FS. The comparisons demonstrated excellent agreement for calculations and measurements within 3%, 1 mm. This study shows that accurate calculations for MERT as delivered with existing photon MLC are feasible and allows the opportunity to take advantage of the dynamic leaf motion capabilities and control systems, to provide conformal dose distributions.

Adaptive brachytherapy treatment planning for cervical cancer using FDG-PET.

PURPOSE: A dosimetric study was conducted to compare intracavitary brachytherapy using both a conventional and a custom loading intended to cover a positron emission tomography (PET)-defined tumor volume in patients with cervix cancer. METHODS AND MATERIALS: Eleven patients who underwent an [(18)F]-fluoro-deoxy-D-glucose (FDG)-PET in conjunction with their first, middle, or last brachytherapy treatment were included in this prospective study. A standard plan that delivers 6.5 Gy to point A under ideal conditions was compared with an optimized plan designed to conform the 6.5-Gy isodose surface to the PET defined volume. RESULTS: A total of 31 intracavitary brachytherapy treatments in conjunction with an FDG-PET were performed. The percent coverage of the target isodose surface for the first implant with and without optimization was 73% and 68% (p = 0.21). The percent coverage of the target isodose surface for the mid/final implant was 83% and 70% (p = 0.02), respectively. The dose to point A was higher with the optimized plans for both the first implant (p = 0.02) and the mid/last implants (p = 0.008). The dose to 2 cm(3) and 5 cm(3) of both the bladder and rectum were not significantly different. CONCLUSIONS: FDG-PET based treatment planning allowed for improved dose coverage of the tumor without significantly increasing the dose to the bladder and rectum.

Retrospective monte carlo dose calculations with limited beam weight information.

An important unresolved issue in outcomes analysis for lung complications is the effect of poor or completely lacking heterogeneity corrections in previously archived treatment plans. To estimate this effect, we developed a novel method based on Monte Carlo (MC) dose calculations which can be applied retrospectively to RTOG/AAPM-style archived treatment plans (ATP). We applied this method to 218 archived nonsmall cell lung cancer lung treatment plans that were originally calculated either without heterogeneity corrections or with primitive corrections. To retrospectively specify beam weights and wedges, beams were broken into Monte Carlo-generated beamlets, simulated using the VMC++ code, and mathematical optimization was used to match the archived water-based dose distributions. The derived beam weights (and any wedge effects) were then applied to Monte Carlo beamlets regenerated based on the patient computed tomography densities. Validation of the process was performed against five comparable lung treatment plans generated using a commercial convolution/superposition implementation. For the application here (normal lung, esophagus, and planning target volume dose distributions), the agreement was very good. Resulting MC and convolution/superposition values were similar when dose distributions without heterogeneity corrections or dose distributions with corrections were compared. When applied to the archived plans (218), the average absolute percent difference between water-based MC and water-based ATPs, for doses above 2.5% of the maximum dose was 1.8+/-0.6%. The average absolute percent difference between heterogeneity-corrected MC and water-based ATPs increased to 3.1+/-0.9%. The average absolute percent difference between the MC heterogeneity-corrected and the ATP heterogeneity-corrected dose distributions was 3.8+/-1.6% (available in 132/218 archives). The entire dose-volume-histograms for lung, tumor, and esophagus from the different calculation methods, as well as specific dose metrics, were compared. The average difference in maximum lung dose between water-based ATPs and heterogeneity-corrected MC dose distributions was -1.0+/-2.1 Gy. Potential errors in relying on primitive heterogeneity corrections are most evident from a comparison of maximum lung doses, for which the average MC heterogeneity-corrected values were 5.3+/-2.8 Gy less than the ATP heterogeneity-corrected values. We have demonstrated that recalculation of archived dose distributions, without explicit information about beam weights or wedges, is feasible using beamlet-based optimization methods. The method provides heterogeneity-corrected dose data consistent with convolution-superposition calculations and is one feasible approach for improving dosimetric data for outcomes analyses.

Multivariable modeling of radiotherapy outcomes, including dose-volume and clinical factors.

PURPOSE: The probability of a specific radiotherapy outcome is typically a complex, unknown function of dosimetric and clinical factors. Current models are usually oversimplified. We describe alternative methods for building multivariable dose-response models. METHODS: Representative data sets of esophagitis and xerostomia are used. We use a logistic regression framework to approximate the treatment-response function. Bootstrap replications are performed to explore variable selection stability. To guard against under/overfitting, we compare several analytical and data-driven methods for model-order estimation. Spearman's coefficient is used to evaluate performance robustness. Novel graphical displays of variable cross correlations and bootstrap selection are demonstrated. RESULTS: Bootstrap variable selection techniques improve model building by reducing sample size effects and unveiling variable cross correlations. Inference by resampling and Bayesian approaches produced generally consistent guidance for model order estimation. The optimal esophagitis model consisted of 5 dosimetric/clinical variables. Although the xerostomia model could be improved by combining clinical and dose-volume factors, the improvement would be small. CONCLUSIONS: Prediction of treatment response can be improved by mixing clinical and dose-volume factors. Graphical tools can mitigate the inherent complexity of multivariable modeling. Bootstrap-based variable selection analysis increases the reliability of reported models. Statistical inference methods combined with Spearman's coefficient provide an efficient approach to estimating optimal model order.

Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters.

PURPOSE: To determine the clinical, dosimetric, and spatial parameters that correlate with radiation pneumonitis. METHODS AND MATERIALS: Patients treated with high-dose radiation for non-small-cell lung cancer with three-dimensional treatment planning were reviewed for clinical information and radiation pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible patients were recovered. Treatment plan information, including parameters defining tumor position and dose-volume parameters, was extracted from non-heterogeneity-corrected dose distributions. Correlation to RP events was assessed by Spearman's rank correlation coefficient (R). Mathematical models were generated that correlate with RP. RESULTS: Of 219 patients, 52 required treatment for RP (median interval, 142 days). Tumor location was the most highly correlated parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were correlated with RP. Models most frequently selected by bootstrap resampling included tumor position, maximum dose, and D35 (minimum dose to the 35% volume receiving the highest doses) (R = 0.28). The most frequently selected two- or three-parameter models outperformed commonly used metrics, including V20 (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R = 0.18). CONCLUSIONS: Inferior tumor position was highly correlated with pneumonitis events within our population. Models that account for inferior tumor position and dosimetric information, including both high- and low-dose regions (D(35), International Commission on Radiation Units and Measurements maximum dose), risk-stratify patients more accurately than any single dosimetric or clinical parameter.

Deblurring of breathing motion artifacts in thoracic PET images by deconvolution methods.

In FDG-PET imaging of thoracic tumors, blurring due to breathing motion often significantly degrades the quality of the observed image, which then obscures the tumor boundary. We demonstrate a deblurring technique that combines patient-specific motion estimates of tissue trajectories with image deconvolution techniques, thereby partially eliminating breathing-motion induced artifacts. Two data sets were used to evaluate the methodology including mobile phantoms and clinical images. The clinical images consist of PET/CT co-registered images of patients diagnosed with lung cancer. A breathing motion model was used to locally estimate the location-dependent tissue location probability function (TLP) due to breathing. The deconvolution process is carried by an expectation-maximization (EM) iterative algorithm using the motion-based TLP. Several methods were used to improve the robustness of the deblurring process by mitigating noise amplification and compensating for motion estimate uncertainties. The mobile phantom study with controlled settings demonstrated significant reduction in underestimation error of concentration in high activity case without significant superiority between the different applied methods. In case of medium activity concentration (moderate noise levels), less improvement was reported (10%-15% reduction in underestimation error relative to 15%-20% reduction in high concentration). Residual denoising using wavelets offered the best performance for this case. In the clinical data case, the image spatial resolution was significantly improved, especially in the direction of greatest motion (cranio-caudal). The EM algorithm converged within 15 and 5 iterations in the large and small tumor cases, respectively. A compromise between a figure-of-merit and entropy minimization was suggested as a stopping criterion. Regularization techniques such as wavelets and Bayesian methods provided further refinement by suppressing noise amplification. Our initial results show that the proposed method provides a feasible framework for improving PET thoracic images, without the need for gated/4-D PET imaging, when 4-D CT is available to estimate tumor motion.

Progress toward a microradiation therapy small animal conformal irradiator.

Microradiation therapy (microRT) systems are being designed to provide conformal radiation therapy to small animals enabling quantitative radiation response evaluation. We used a Monte Carlo approach to estimate the radiation dose distributions from proposed blueprints and developed a beam model to aid in the microRT system design process. This process was applied to a prototype irradiator that uses a small (3 mm long and 3 mm in diameter), cylindrical, high-activity 192Ir source delivering the radiation beam using custom-fabricated tungsten collimators. The BEAMnrc Monte Carlo code was used to simulate dose distributions from these prototype collimators. Simulations were performed at three source-to-surface distances (50, 60, and 70 mm), and with five circular field sizes (5, 7.5, 10, 12.5, and 15 mm). A dose to a 50 X 50 X 50 mm3 water phantom with 1 X 1 X 1 mm3 voxel spacing was computed. A multiparameter dose calculation algorithm was developed to efficiently and accurately calculate doses for treatment planning exercises. The parametrization was selected so that the parameters varied smoothly as a function of depth, source-to-surface distance, and field size, allowing interpolation for geometries that were not simulated using the Monte Carlo simulation. Direct comparison of the model with the Monte Carlo simulations showed that the variations were within 5% error for field sizes larger than 10 mm, and up to 10% for smaller field sizes.

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

PURPOSE: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. METHODS: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. RESULTS: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. CONCLUSIONS: A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.

Sequential FDG-PET brachytherapy treatment planning in carcinoma of the cervix.

PURPOSE: To evaluate the utility of sequential (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brachytherapy treatment planning in patients with carcinoma of the cervix. METHODS AND MATERIALS: Twenty-four patients with carcinoma of the cervix were included in this prospective study. The clinical stage of their disease was Ib (7), IIa (1), IIb (7), and IIIb (9). Patients were treated with irradiation and brachytherapy, with the majority receiving concurrent weekly cisplatin chemotherapy. Patients underwent diagnostic FDG-PET imaging before treatment, sequential FDG-PET brachytherapy imaging during treatment, and diagnostic FDG-PET 3 months after treatment completion. Delineation of the gross tumor volume, bladder, and rectum was performed for all scans using a commercially available treatment-planning system. Actual treatment delivery was based on two-dimensional orthogonal planning. RESULTS: The mean gross tumor volume and percent coverage by the target isodose surface for the initial, mid, and last implant were 37 cm3, 17 cm3, and 10 cm3 and 68%, 76%, and 79%, respectively. Nine of 11 patients were found to have continued decrease in tumor volume as measured by FDG-PET, with 3 patients having complete regression of their tumor before treatment was completed. The maximal bladder and rectal doses obtained from three-dimensional dose-volume histograms were significantly higher than the International Commission on Radiation Units and Measurements Report 38 bladder and rectal points obtained by two-dimensional treatment-planning. CONCLUSIONS: Sequential FDG-PET brachytherapy imaging identifies the tumor response in individual patients, potentially making patient-specific brachytherapy treatment planning possible.

Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy.

PURPOSE: We investigated the factors that affect salivary function after head-and-neck radiotherapy (RT), including parotid gland dose-volume effects, potential compensation by less-irradiated gland tissue, and functional recovery over time. METHODS AND MATERIALS: Sixty-five patients with head-and-neck tumors were enrolled in a prospective salivary function study. RT was delivered using intensity-modulated RT (n = 45), forward-planning three-dimensional conformal RT (n = 14), or three-dimensional conformal RT with an intensity-modulated RT boost (n = 6). Whole salivary flow was measured before therapy and at 6 months (n = 61) and 12 months (n = 31) after RT. A wide variety of dose-volume models to predict post-RT salivary function were tested. Xerostomia was defined according to the subjective, objective, management, analytic (SOMA) criteria as occurring when posttreatment salivary function was < 25% of the pretreatment function. Multivariate logistic regression analysis was used to assess the combined effect of dose-volume, patient-, and treatment-related factors. RESULTS: A significant correlation was observed between the relative quality-of-life scores and relative stimulated saliva values at 6 months after RT (Spearman's correlation coefficient [R(s)] = 0.46, p < 0.001). The dose-volume factors were by far the strongest correlates with stimulated saliva flow, although other factors showed modest significance in multimetric models (chemotherapy, gender, and Karnofsky performance status). Several fitted dose-volume models provided a good mathematical description of the data. Significant noise in the salivary measurements (repeated measurement coefficient of variation was 27% in normal subjects) precluded selection of any one of the models presented solely on the basis of the objective fit criteria. Nevertheless, the mean dose-exponential model, in which each parotid gland's relative salivary gland function equaled exp(-A x mean gland dose), with A equal to 0.054/Gy (68% confidence interval 0.052-0.059), provided a good representation of the data and was incorporated into our multimetric analysis. Using that model, we estimated that a mean parotid dose of 25.8 Gy, on average, was likely to reduce a single parotid gland's flow to 25% of its pretreatment value, regardless of the treatment delivery method. Significant correlations were observed between a logistic multivariate model (incorporating the mean dose-exponential equation, gender, and Karnofsky performance status) and stimulated saliva flow at 6 months (R(s) = 0.73), stimulated saliva flow at 12 months (R(s) = 0.54), and quality-of-life score at 6 months (R(s) = 0.35) after RT. CONCLUSION: Stimulated parotid salivary gland dose-volume models strongly correlated with both stimulated salivary function and quality-of-life scores at 6 months after RT. The mean stimulated saliva flow rates improved from 6 to 12 months after RT. Salivary function, in each gland, appeared to be lost exponentially at a rate of approximately 5%/1 Gy of mean dose. Additional research is necessary to distinguish among the models for use in treatment planning. The incidence of xerostomia was significantly decreased when the mean dose of at least one parotid gland was kept to < 25.8 Gy with conventional fractionation. However, even lower mean doses imply increased late salivary function.