Dosimetric characterization of a new surface-conforming electron MLC prototype.

The purpose is to reduce normal tissue radiation toxicity for electron therapy through the creation of a surface-conforming electron multileaf collimator (SCEM). The SCEM combines the benefits of skin collimation, electron conformal radiotherapy, and modulated electron radiotherapy. An early concept for the SCEM was constructed. It consists of leaves that protrude towards the patient, allowing the leaves to conform closely to irregular patient surfaces. The leaves are made of acrylic to decrease bremsstrahlung, thereby decreasing the out-of-field dose. Water tank scans were performed with the SCEM in place for various field sizes for all available electron energies (6, 9, 12, and 15 MeV) with a 0.5 cm air gap to the water surface at 100 cm source-to-surface distance (SSD). These measurements were compared with Cerrobend cutouts with the field size-matched at 100 and 110 cm SSD. Output factor measurements were taken in solid water for each energy at dmax for both the cerrobend cutouts and SCEM at 100 cm SSD. Percent depth dose (PDD) curves for the SCEM shifted shallower for all energies and field sizes. The SCEM also produced a higher surface dose relative to Cerrobend cutouts, with the maximum being a 9.8% increase for the 3 cm × 9 cm field at 9 MeV. When compared to the Cerrobend cutouts at 110 cm SSD, the SCEM showed a significant decrease in the penumbra, particularly for lower energies (i.e., 6 and 9 MeV). The SCEM also showed reduced out-of-field dose and lower bremsstrahlung production than the Cerrobend cutouts. The SCEM provides significant improvement in the penumbra and out-of-field dose by allowing collimation close to the skin surface compared to Cerrobend cutouts. However, the added scatter from the SCEM increases shallow PDD values. Future work will focus on reducing this scatter while maintaining the penumbra and out-of-field benefits the SCEM has over conventional collimation.

Machine learning models to predict the delivered positions of Elekta multileaf collimator leaves for volumetric modulated arc therapy.

PURPOSE: Accurate positioning of multileaf collimator (MLC) leaves during volumetric modulated arc therapy (VMAT) is essential for accurate treatment delivery. We developed a linear regression, support vector machine, random forest, extreme gradient boosting (XGBoost), and an artificial neural network (ANN) for predicting the delivered leaf positions for VMAT plans. METHODS: For this study, 160 MLC log files from 80 VMAT plans were obtained from a single institution treated on 3 Elekta Versa HD linear accelerators. The gravity vector, X1 and X2 jaw positions, leaf gap, leaf position, leaf velocity, and leaf acceleration were extracted and used as model inputs. The models were trained using 70% of the log files and tested on the remaining 30%. Mean absolute error (MAE), root mean square error (RMSE), the coefficient of determination R2 , and fitted line plots showing the relationship between delivered and predicted leaf positions were used to evaluate model performance. RESULTS: The models achieved the following errors: linear regression (MAE = 0.158 mm, RMSE = 0.225 mm), support vector machine (MAE = 0.141 mm, RMSE = 0.199 mm), random forest (MAE = 0.161 mm, RMSE = 0.229 mm), XGBoost (MAE = 0.185 mm, RMSE = 0.273 mm), and ANN (MAE = 0.361 mm, RMSE = 0.521 mm). A significant correlation between a plan's gamma passing rate (GPR) and the prediction errors of linear regression, support vector machine, and random forest is seen (p < 0.045). CONCLUSIONS: We examined various models to predict the delivered MLC positions for VMAT plans treated with Elekta linacs. Linear regression, support vector machine, random forest, and XGBoost achieved lower errors than ANN. Models that can accurately predict the individual leaf positions during treatment can help identify leaves that are deviating from the planned position, which can improve a plan's GPR.

End to end comparison of surface-guided imaging versus stereoscopic X-rays for the SRS treatment of multiple metastases with a single isocenter using 3D anthropomorphic gel phantoms.

INTRODUCTION: Two end-to-end tests evaluate the accuracy of a surface-guided radiation therapy (SGRT) system (CRAD Catalyst HD) for position verification in comparison to a stereoscopic x-ray imaging system (Brainlab Exactrac ) for single-isocenter, multiple metastases stereotactic radiosurgery (SRS) using 3D polymer gel inserts. MATERIALS AND METHODS: A 3D-printed phantom (Prime phantom, RTsafe PC, Athens, Greece) with two separate cylindrical polymer gel inserts were immobilized in open-face masks and treated with a single isocentric, multitarget SRS plan. Planning was done in Brainlab (Elements) to treat five metastatic lesions in one fraction, and initial setup was done using cone beam computed tomography. Positional verification was done using orthogonal X-ray imaging (Brainlab Exactrac) and/or a surface imaging system (CRAD Catalyst HD, Uppsala, Sweden), and shift discrepancies were recorded for each couch angle. Forty-two hours after irradiation, the gel phantom was scanned in a 1.5 Tesla MRI, and images were fused with the patient computed tomography data/structure set for further analysis of spatial dose distribution. RESULTS: Discrepancies between the CRAD Catalyst HD system and Brainlab Exactrac were <1 mm in the translational direction and <0.5° in the angular direction at noncoplanar couch angles. Dose parameters (DMean% , D95% ) and 3D gamma index passing rates were evaluated for both setup modalities for each planned target volume (PTV) at a variety of thresholds: 3%/2 mm (Exactrac≥93.1% and CRAD ≥87.2%), 5%/2 mm (Exactrac≥95.6% and CRAD ≥94.6%), and 5%/1 mm (Exactrac≥81.8% and CRAD ≥83.7%). CONCLUSION: Dose metrics for a setup with surface imaging was found to be consistent with setup using x-ray imaging, demonstrating high accuracy and reproducibility for treatment delivery. Results indicate the feasibility of using surface imaging for position verification at noncoplanar couch angles for single-isocenter, multiple-target SRS using end-to-end quality assurance (QA) testing with 3D polymer gel dosimetry.

Demographic responses of Tribolium castaneum (Coleoptera: Tenebrionidae) to different temperatures in soft wheat flour.

The red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) is one of the most dangerous insects of a wide spectrum of stored products around the globe. The population growth of this species is affected by temperature. However, there are no data on comparative demographic parameters (i.e., net reproductive rate, intrinsic rate of increase, finite rate of increase, mean generation time and doubling time) in different temperatures, parameters that allow the in-depth exploration of its survival, mortality and reproduction patterns. This study evaluated egg-to-adult development, adult mortality and female fecundity on white soft wheat flour at 20, 25, 30 and 32.5 °C. The net reproductive rate increased from 0.08 females/female at 20 °C to 11.77 females/female at 25 °C and 102.07 females/female at 30 °C, followed by a decrease to 10.73 females/female at 32.5 °C. The lowest values of the intrinsic rate of increase and the finite rate of increase were observed at 20 °C (- 0.0105 females/female/day and 0.9895, respectively) and the highest at 30 °C (0.0348 females/female/day and 1.0354, respectively). While the mean generation time did not differ significantly between 20 and 25 °C (249.9 and 225.5 days, respectively), this decreased to 132.8 and 115.1 days at 30 and 32.5 °C, respectively. The value of the doubling time was negative at 20 °C (- 67.5 days), increased to 19.9, 34.0 and 63.9 days at 30, 32.5 and 25 °C, respectively. Using the non-linear Briere model, the lower threshold for T. castaneum population increase was estimated to be 22.2 °C, the upper threshold at 33.2 °C, and the temperature for maximum growth rate was 30.1 °C. Survival analysis indicated that temperature also affected the mortality risk of T. castaneum. The mean survival time increased from 112.1 days at 20 °C to 462.4 days at 25 °C, followed by a decrease to 206.5 and 64.5 days at 30 and 32.5 °C, respectively. We expect these results to be useful for the prediction of the population growth, the potential expansion and consequently management of T. castaneum.

On the evaluation of mobile target trajectory between four-dimensional computer tomography and four-dimensional cone-beam computer tomography.

PURPOSE: For mobile lung tumors, four-dimensional computer tomography (4D CT) is often used for simulation and treatment planning. Localization accuracy remains a challenge in lung stereotactic body radiation therapy (SBRT) treatments. An attractive image guidance method to increase localization accuracy is 4D cone-beam CT (CBCT) as it allows for visualization of tumor motion with reduced motion artifacts. However, acquisition and reconstruction of 4D CBCT differ from that of 4D CT. This study evaluates the discrepancies between the reconstructed motion of 4D CBCT and 4D CT imaging over a wide range of sine target motion parameters and patient waveforms. METHODS: A thorax motion phantom was used to examine 24 sine motions with varying amplitudes and cycle times and seven patient waveforms. Each programmed motion was imaged using 4D CT and 4D CBCT. The images were processed to auto segment the target. For sine motion, the target centroid at each phase was fitted to a sinusoidal curve to evaluate equivalence in amplitude between the two imaging modalities. The patient waveform motion was evaluated based on the average 4D data sets. RESULTS: The mean difference and root-mean-square-error between the two modalities for sine motion were -0.35 ± 0.22 and 0.60 mm, respectively, with 4D CBCT slightly overestimating amplitude compared with 4D CT. The two imaging methods were determined to be significantly equivalent within ±1 mm based on two one-sided t tests (p < 0.001). For patient-specific motion, the mean difference was 1.5 ± 2.1 (0.8 ± 0.6 without outlier), 0.4 ± 0.3, and 0.8 ± 0.6 mm for superior/inferior (SI), anterior/posterior (AP), and left/right (LR), respectively. CONCLUSION: In cases where 4D CT is used to image mobile tumors, 4D CBCT is an attractive localization method due to its assessment of motion with respect to 4D CT, particularly for lung SBRT treatments where accuracy is paramount.

Incorporating biological modeling into patient-specific plan verification.

PURPOSE: Dose-volume histogram (DVH) measurements have been integrated into commercially available quality assurance systems to provide a metric for evaluating accuracy of delivery in addition to gamma analysis. We hypothesize that tumor control probability and normal tissue complication probability calculations can provide additional insight beyond conventional dose delivery verification methods. METHODS: A commercial quality assurance system was used to generate DVHs of treatment plan using the planning CT images and patient-specific QA measurements on a phantom. Biological modeling was performed on the DVHs produced by both the treatment planning system and the quality assurance system. RESULTS: The complication-free tumor control probability, P+ , has been calculated for previously treated intensity modulated radiotherapy (IMRT) patients with diseases in the following sites: brain (-3.9% ± 5.8%), head-neck (+4.8% ± 8.5%), lung (+7.8% ± 1.3%), pelvis (+7.1% ± 12.1%), and prostate (+0.5% ± 3.6%). CONCLUSION: Dose measurements on a phantom can be used for pretreatment estimation of tumor control and normal tissue complication probabilities. Results in this study show how biological modeling can be used to provide additional insight about accuracy of delivery during pretreatment verification.

An evaluation of the stability of image quality parameters of Elekta X-ray volume imager and iViewGT imaging systems.

INTRODUCTION: A robust image quality assurance and analysis methodology for image-guided localization systems is crucial to ensure the accurate localization and visualization of target tumors. In this study, the long-term stability of selected image parameters was assessed and evaluated for the cone-beam computed tomography (CBCT) mode, planar radiographic kV mode, and the radiographic MV mode of an Elekta VersaHD. MATERIALS AND METHODS: The CATPHAN, QckV-1, and QC-3 phantoms were used to evaluate the image quality parameters. The planar radiographic images were analyzed in PIPSpro™ with spatial resolution (f30, f40, f50), contrast to noise ratio (CNR) and noise being recorded. For XVI CBCT, Head and Neck Small20 (S20) and Pelvis Medium20 (M20) standard acquisition modes were evaluated for uniformity, noise, spatial resolution, and HU constancy. Dose and kVp for the XVI were recorded using the Unfors RaySafe Xi system with the R/F low detector for the kV planar radiographic mode. For each metric, values were normalized to the mean and the standard deviations were recorded. RESULTS: A total of 30 measurements were performed on a single Elekta VersaHD linear accelerator over an 18-month period without significant adjustment or recalibration to the XVI or iViewGT systems during the evaluated time frame. For the planar radiographic spatial resolution, the normalized standard deviation values of the f30, f40, and f50 were 0.004, 0.003, and 0.003 and 0.015, 0.009, and 0.017 for kV and MV, respectively. The average recorded dose for kV was 67.96 µGy. The standard deviations of the evaluated metrics for the S20 acquisition were 0.083(f30), 0.058(f40), 0.056(f50), 0.021(Water/poly-HU constancy), 0.029(uniformity) and 0.028(noise). The standard deviations for the M20 acquisition were 0.093(f30), 0.043(f40), 0.037(f50), 0.016(Water/poly-HU constancy), 0.010(uniformity) and 0.011(Noise). CONCLUSION: A study was performed to assess the stability of the basic image quality parameters recommended by TG-142 for the Elekta XVI and iViewGT imaging systems. The two systems show consistent imaging and dosimetric properties over the evaluated time frame.

Do temperature, relative humidity and interspecific competition alter the population size and the damage potential of stored-product insect pests? A hierarchical multilevel modeling approach.

The premises of stored agricultural products and food consists of a complex ecosystem in which several pests can seriously affect the quality and quantity of the products. In this study we utilize a 4-level hierarchical linear multilevel model in order to assess the effect of temperature, relative humidity (RH) and interspecific competition on the population size and damage potential of the larger grain borer, Prostephanus truncatus (Horn) (Coleoptera: Bostrychidae) and the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae). As RH was increased, we observed higher percentage of live insects, while increased levels of temperature significantly decreased the percentage of live insects. The combination of R. dominica and P. truncatus lead to reduction of the percentages of live insects in comparison to single species treatments. However, P. truncatus is more damaging than R. dominica in maize, based on the proportion of damaged kernels which were infested by each insect species. We expect our results to have bearing in the management of these species.

Investigation of error detection capabilities of phantom, EPID and MLC log file based IMRT QA methods.

A patient specific quality assurance (QA) should detect errors that originate anywhere in the treatment planning process. However, the increasing complexity of treatment plans has increased the need for improvements in the accuracy of the patient specific pretreatment verification process. This has led to the utilization of higher resolution QA methods such as the electronic portal imaging device (EPID) as well as MLC log files and it is important to know the types of errors that can be detected with these methods. In this study, we will compare the ability of three QA methods (Delta4 ®, MU-EPID, Dynalog QA) to detect specific errors. Multileaf collimator (MLC) errors, gantry angle, and dose errors were introduced into five volumetric modulated arc therapy (VMAT) plans for a total of 30 plans containing errors. The original plans (without errors) were measured five times with each method to set a threshold for detectability using two standard deviations from the mean and receiver operating characteristic (ROC) derived limits. Gamma passing percentages as well as percentage error of planning target volume (PTV) were used for passing determination. When applying the standard 95% pass rate at 3%/3 mm gamma analysis errors were detected at a rate of 47, 70, and 27% for the Delta4 , MU-EPID and Dynalog QA respectively. When using thresholds set at 2 standard deviations from our base line measurements errors were detected at a rate of 60, 30, and 47% for the Delta4 , MU-EPID and Dynalog QA respectively. When using ROC derived thresholds errors were detected at a rate of 60, 27, and 47% for the Delta4 , MU-EPID and Dynalog QA respectively. When using dose to the PTV and the Dynalog method 11 of the 15 small MLC errors were detected while none were caught using gamma analysis. A combination of the EPID and Dynalog QA methods (scaling Dynalog doses using EPID images) matches the detection capabilities of the Delta4 by adding additional comparison metrics. These additional metrics are vital in relating the QA measurement to the dose received by the patient which is ultimately what is being confirmed.

Comparison of initial patient setup accuracy between surface imaging and three point localization: A retrospective analysis.

PURPOSE: Historically, the process of positioning a patient prior to imaging verification used a set of permanent patient marks, or tattoos, placed subcutaneously. After aligning to these tattoos, plan specific shifts are applied and the position is verified with imaging, such as cone-beam computed tomography (CBCT). Due to a variety of factors, these marks may deviate from the desired position or it may be hard to align the patient to these marks. Surface-based imaging systems are an alternative method of verifying initial positioning with the entire skin surface instead of tattoos. The aim of this study was to retrospectively compare the CBCT-based 3D corrections of patients initially positioned with tattoos against those positioned with the C-RAD CatalystHD surface imager system. METHODS: A total of 6000 individual fractions (600-900 per site per method) were randomly selected and the post-CBCT 3D corrections were calculated and recorded. For both positioning methods, four common treatment site combinations were evaluated: pelvis/lower extremities, abdomen, chest/upper extremities, and breast. Statistical differences were evaluated using a paired sample Wilcoxon signed-rank test with significance level of <0.01. RESULTS: The average magnitudes of the 3D shift vectors for tattoos were 0.9 ± 0.4 cm, 1.0 ± 0.5 cm, 0.9 ± 0.6 cm and 1.4 ± 0.7 cm for the pelvis/lower extremities, abdomen, chest/upper extremities and breast, respectively. For the CatalystHD, the average magnitude of the 3D shifts for the pelvis/lower extremities, abdomen, chest/upper extremities and breast were 0.6 ± 0.3 cm, 0.5 ± 0.3 cm, 0.5 ± 0.3 cm and 0.6 ± 0.2 cm, respectively. Statistically significant differences (P < 0.01) in the 3D shift vectors were found for all four sites. CONCLUSION: This study shows that the overall 3D shift corrections for patients initially aligned with the C-RAD CatalystHD were significantly smaller than those aligned with subcutaneous tattoos. Surface imaging systems can be considered a viable option for initial patient setup and may be preferable to permanent marks for specific clinics and patients.

Pinnacle3 modeling and end-to-end dosimetric testing of a Versa HD linear accelerator with the Agility head and flattening filter-free modes.

The Elekta Versa HD incorporates a variety of upgrades to the line of Elekta linear accelerators, primarily including the Agility head and flattening filter-free (FFF) photon beam delivery. The completely distinct dosimetric output of the head from its predecessors, combined with the FFF beams, requires a new investigation of modeling in treatment planning systems. A model was created in Pinnacle3 v9.8 with the commissioned beam data. A phantom consisting of several plastic water and Styrofoam slabs was scanned and imported into Pinnacle3, where beams of different field sizes, source-to-surface distances (SSDs), wedges, and gantry angles were devised. Beams included all of the available photon energies (6, 10, 18, 6FFF, and 10 FFF MV), as well as the four electron energies commissioned for clinical use (6, 9, 12, and 15 MeV). The plans were verified at calculation points by measurement with a calibrated ionization chamber. Homogeneous and hetero-geneous point-dose measurements agreed within 2% relative to maximum dose for all photon and electron beams. AP photon open field measurements along the central axis at 100 cm SSD passed within 1%. In addition, IMRT testing was also performed with three standard plans (step and shoot IMRT, as well as a small- and large-field VMAT plan). The IMRT plans were delivered on the Delta4 IMRT QA phantom, for which a gamma passing rate was > 99.5% for all plans with a 3% dose deviation, 3 mm distance-to-agreement, and 10% dose threshold. The IMRT QA results for the first 23 patients yielded gamma passing rates of 97.4% ± 2.3%. Such testing ensures confidence in the ability of Pinnacle3 to model photon and electron beams with the Agility head.

Biocompatible colloidal dispersions as potential formulations of natural pyrethrins: a structural and efficacy study.

Biocompatible colloidal dispersions of the micro- and nanoemulsion type based on lemon oil terpenes, polysorbates, water, and glycerol were used for the formulation of pyrethrins, botanical insecticides derived from the white pyrethrum daisy, Tanacetum cinerariifolium. The proposed formulation is based on pyrethrin-containing water-in-oil (W/O) microemulsions that could be diluted in one step with an aqueous phase to obtain kinetically stable oil-in-water (O/W) nanoemulsions. Structural characteristics of the micro- and nanoemulsions were evaluated by electron paramagnetic resonance (EPR) spectroscopy, dynamic light scattering (DLS), small angle X-ray scattering (SAXS), and electrical conductivity. Dynamic properties of the surfactant monolayer as evidenced by EPR measurements were affected by the water content, the surfactant, and also the presence of the biocide. DLS and SAXS experiments of the nanoemulsions indicated the existence of two populations of oil droplets dispersed in the aqueous phase, globular droplets of 36-37 nm in diameter, and also larger droplets with diameters >150 nm. All of the applied techniques for structural determination revealed the participation of the biocide in the nanostructure. The insecticidal effect of the encapsulated natural pyrethrin was evaluated in laboratory bioassays upon a target-insect pest, the cotton aphid Aphis gossypii Glover (Hemiptera: Aphididae) in eggplant, and was found to be increased compared to the commercial pyrethrin formulation.

An evaluation of the stability of image-quality parameters of Varian on-board imaging (OBI) and EPID imaging systems.

Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of regions of interest within the patient. In this study, the temporal stability of selected image parameters was assessed and evaluated for kV CBCT mode, planar radiographic kV, and MV modes. The motivation of the study was to better characterize the temporal variability in specific image-quality parameters. The CATPHAN, QckV-1, and QC-3 phantoms were used to evaluate the image-quality parameters of the imaging systems on a Varian Novalis Tx linear accelerator. The planar radiographic images were analyzed in PIPSpro with high-contrast spatial resolution (f30, f40,f50 lp/mm) being recorded. For OBI kV CBCT, high-quality head full-fan acquisition and pelvis half-fan acquisition modes were evaluated for uniformity, noise, spatial resolution, HU constancy, and geometric distortion. Dose and X-ray energy for the OBI were recorded using the Unfors RaySafe Xi system with the R/F High Detector for kV planar radiographic and the CT detector for kV CBCT. Dose for the MV EPID was recorded using a PTW975 Semiflex ion chamber, PTW UNIDOS electrometer, and CNMC Plastic Water. For each image-quality parameter, values were normalized to the mean, and the normalized standard deviations were recorded to evaluate the parameter's temporal variability. For planar radiographic modes, the normalized standard deviations of the spatial resolution (f30, f40, & f50) were 0.015, 0.008, 0.004 lp/mm and 0.006, 0.009, 0.018 lp/mm for the kV and MV, respectively. The normalized standard deviation of dose for kV and MV were 0.010 mGy and 0.005mGy, respectively. The standard deviations for full- and half-fan kV CBCT modes were averaged together. The following normalized standard deviations for each kV CBCT parameter were: 0.075 HU (uniformity), 0.071 HU (noise), 0.006mm (AP-geometric distortion), 0.005 mm (LAT-geometric distortion), 0.058mm (slice thickness), 0.124 (f50), 0.031 (HU constancy - Lung), 0.063 (HU constancy- Water), 0.020 (HU constancy - Bone), 0.006 mGy (Dose - Center), 0.004 mGy (Dose -Periphery). Using control chart analysis, institutional QA tolerances were reported as warning and action thresholds based on 1σ and 2σ thresholds. A study was performed to characterize the stability of image-quality parameters recommended by AAPM Task Group-142 for the Varian OBI and EPID imaging systems. Both imaging systems show consistent imaging and dosimetric properties over the evaluated time frame.

Anatomy-based, patient-specific VMAT QA using EPID or MLC log files.

In this project, we investigated the use of an electronic portal imaging device (EPID), together with the treatment planning system (TPS) and MLC log files, to determine the delivered doses to the patient and evaluate the agreement between the treatment plan and the delivered dose distribution. The QA analysis results are presented for 15 VMAT patients using the EPID measurements, the ScandiDos Delta4 dosimeter, and the beam fluence calculated from the multileaf collimator (MLC) log file. EPID fluence images were acquired in continuous acquisition mode for each of the patients and they were processed through an in-house MATLAB program to create an opening density matrix (ODM), which was used as the input fluence for the dose calculation in the TPS (Pinnacle3). The EPID used in this study was the aSi1000 Varian on a Novalis TX linac equipped with high-definition MLC. The actual MLC positions and gantry angles were retrieved from the MLC log files and the data were used to calculate the delivered dose distributions in Pinnacle. The resulting dose distributions were then compared against the corresponding planned dose distributions using the 3D gamma index with 3 mm/3% passing criteria. The ScandiDos Delta4 phantom was also used to measure a 2D dose distribution for all the 15 patients and a 2D gamma was calculated for each patient using the Delta4 software. The average 3D gamma using the EPID images was 96.1% ± 2.2%. The average 3D gamma using the log files was 98.7% ± 0.5%. The average 2D gamma from the Delta4 was 98.1% ± 2.1%. Our results indicate that the use of the EPID, combined with MLC log files and a TPS, is a viable method for QA of VMAT plans.

Comparing conformal, arc radiotherapy and helical tomotherapy in craniospinal irradiation planning.

Currently, radiotherapy treatment plan acceptance is based primarily on dosimetric performance measures. However, use of radiobiological analysis to assess benefit in terms of tumor control and harm in terms of injury to normal tissues can be advantageous. For pediatric craniospinal axis irradiation (CSI) patients, in particular, knowing the technique that will optimize the probabilities of benefit versus injury can lead to better long-term outcomes. Twenty-four CSI pediatric patients (median age 10) were retrospectively planned with three techniques: three-dimensional conformal radiation therapy (3D CRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). VMAT plans consisted of one superior and one inferior full arc, and tomotherapy plans were created using a 5.02cm field width and helical pitch of 0.287. Each plan was normalized to 95% of target volume (whole brain and spinal cord) receiving prescription dose 23.4Gy in 13 fractions. Using an in-house MATLAB code and DVH data from each plan, the three techniques were evaluated based on biologically effective uniform dose (D=), the complication-free tumor control probability (P+), and the width of the therapeutically beneficial range. Overall, 3D CRT and VMAT plans had similar values of D= (24.1 and 24.2 Gy), while HT had a D= slightly lower (23.6 Gy). The average values of the P+ index were 64.6, 67.4, and 56.6% for 3D CRT, VMAT, and HT plans, respectively, with the VMAT plans having a statistically significant increase in P+. Optimal values of D= were 28.4, 33.0, and 31.9 Gy for 3D CRT, VMAT, and HT plans, respectively. Although P+ values that correspond to the initial dose prescription were lower for HT, after optimizing the D= prescription level, the optimal P+ became 94.1, 99.5, and 99.6% for 3D CRT, VMAT, and HT, respectively, with the VMAT and HT plans having statistically significant increases in P+. If the optimal dose level is prescribed using a radiobiological evaluation method, as opposed to a purely dosimetric one, the two IMRT techniques, VMAT and HT, will yield largest overall benefit to CSI patients by maximizing tumor control and limiting normal tissue injury. Using VMAT or HT may provide these pediatric patients with better long-term outcomes after radiotherapy.

Development of image quality assurance measures of the ExacTrac localization system using commercially available image evaluation software and hardware for image-guided radiotherapy.

Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of target volumes. In this study, a methodology was developed to assess and evaluate the constancy of the high-contrast spatial resolution, dose, energy, contrast, and geometrical accuracy of the BrainLAB ExacTrac system. An in-house fixation device was constructed to hold the QCkV-1 phantom firmly and reproducibly against the face of the flat panel detectors. Two image sets per detector were acquired using ExacTrac preset console settings over a period of three months. The image sets were analyzed in PIPSpro and the following metrics were recorded: high-contrast spatial resolution (f30, f40, f50 (lp/mm)), noise, and contrast-to-noise ratio. Geometrical image accu- racy was evaluated by assessing the length between to predetermined points of the QCkV-1 phantom. Dose and kVp were recorded using the Unfors RaySafe Xi R/F Detector. The kVp and dose were evaluated for the following: Cranial Standard (CS) (80 kV,80 mA,80 ms), Thorax Standard (TS) (120 kV,160 mA,160 ms), Abdomen Standard (AS) (120 kV,160 mA,130 ms), and Pelvis Standard (PS) (120 kV,160 mA,160 ms). With regard to high-contrast spatial resolution, the mean values of the f30 (lp/mm), f40 (lp/mm) and f50 (lp/mm) for the left detector were 1.39 ± 0.04, 1.24 ± 0.05, and 1.09 ± 0.04, respectively, while for the right detector they were 1.38 ± 0.04, 1.22 ± 0.05, and 1.09 ± 0.05, respectively. Mean CNRs for the left and right detectors were 148 ± 3 and 143 ± 4, respectively. For geometrical accuracy, both detectors had a measured image length of the QCkV-1 of 57.9 ± 0.5 mm. The left detector showed dose measurements of 20.4 ± 0.2 µGy (CS), 191.8 ± 0.7 µGy (TS), 154.2 ± 0.7 µGy (AS), and 192.2 ± 0.6 µGy (PS), while the right detector showed 20.3 ± 0.3 µGy (CS), 189.7 ± 0.8 µGy (TS), 151.0 ± 0.7 µGy (AS), and 189.7 ± 0.8 µGy (PS), respectively. For X-ray energy, the left detector (right X-ray tube) had mean kVp readings of 81.6 ± 0.5 (CS), 122.5 ± 0.5 (TS), 122.0 ± 0.8 (AS), and 122.1 ± 0.7 (PS), and the right detector (left X-ray tube) had 81.6 ± 0.5 (CS), 120.8 ± 0.5 (TS), 120.9 ± 0.6 (AS), and 121.3 ± 0.7 (PS). Run charts were created so that each parameter could be tracked over time and the constancy of the system could be monitored. A methodology was developed to assess the basic image quality parameters recommended by TG-142 for the ExacTrac system. The ExacTrac system shows a consistent dose, kVp, high-contrast spatial resolution, CNR, and geometrical accuracy for each detector over the evaluated timeframe. 

Adaptive experimental design produces superior and more efficient estimates of predator functional response.

Ecological dynamics are strongly influenced by the relationship between prey density and predator feeding behavior-that is, the predatory functional response. A useful understanding of this relationship requires us to distinguish between competing models of the functional response, and to robustly estimate the model parameters. Recent advances in this topic have revealed bias in model comparison, as well as in model parameter estimation in functional response studies, mainly attributed to the quality of data. Here, we propose that an adaptive experimental design framework can mitigate these challenges. We then present the first practical demonstration of the improvements it offers over standard experimental design. Our results reveal that adaptive design can efficiently identify the preferred functional response model among the competing models, and can produce much more precise posterior distributions for the estimated functional response parameters. By increasing the efficiency of experimentation, adaptive experimental design will lead to reduced logistical burden.

The radiobiological P(+) index for pretreatment plan assessment with emphasis on four-dimensional radiotherapy modalities.

PURPOSE: Radiation treatment modalities will continue to emerge that promise better clinical outcomes albeit technologically challenging to implement. An important question facing the radiotherapy community then is the need to justify the added technological effort for the clinical return. Mobile tumor radiotherapy is a typical example, where 4D tumor tracking radiotherapy (4DTRT) has been proposed over the simpler conventional modality for better results. The modality choice per patient can depend on a wide variety of factors. In this work, we studied the complication-free tumor control probability (P(+)) index, which combines the physical complexity of the treatment plan with the radiobiological characteristics of the clinical case at hand and therefore found to be useful in evaluating different treatment techniques and estimating the expected clinical effectiveness of different radiation modalities. METHODS: 4DCT volumes of 18 previously treated lung cancer patients with tumor motion and size ranging from 2 mm to 15 mm and from 4 cc to 462 cc, respectively, were used. For each patient, 4D treatment plans were generated to extract the 4D dose distributions, which were subsequently used with clinically derived radiobiological parameters to compute the P(+) index per modality. RESULTS: The authors observed, on average, a statistically significant increase in P(+) of 3.4% ± 3.8% (p < 0.003) in favor of 4DTRT. There was high variability among the patients with a <0.5% up to 13.4% improvement in P(+). CONCLUSIONS: The observed variability in the improvement of the clinical effectiveness suggests that the relative benefit of tracking should be evaluated on a per patient basis. Most importantly, this variability could be effectively captured in the computed P(+). The index can thus be useful to discriminate and hence point out the need for a complex modality like 4DTRT over another. Besides tumor mobility, a wide range of other factors, e.g., size, location, fractionation, etc., can affect the relative benefits. Application of the P(+) objective is a simple and effective way to combine these factors in the evaluation of a treatment plan.

Investigating the dosimetric and tumor control consequences of prostate seed loss and migration.

PURPOSE: Low dose-rate brachytherapy is commonly used to treat prostate cancer. However, once implanted, the seeds are vulnerable to loss and movement. The goal of this work is to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. METHODS: Five patients were used in this study. For each patient three treatment plans were created using Iodine-125, Palladium-103, and Cesium-131 seeds. The three seeds that were closest to the urethra were identified and modeled as the seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in-house software to perform the dosimetric and radiobiological evaluation. Seed loss was simulated by simultaneously removing 1, 2, or 3 seeds near the urethra 0, 2, or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21, or 28 days after the implant. RESULTS: Loss of one, two or three seeds through the urethra results in a D(90) reduction of 2%, 5%, and 7% loss, respectively. Due to delayed loss of peripheral seeds, the dosimetric effects are less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal. CONCLUSIONS: The goal of this work was to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction of D(90) coverage. However, for the patients in this study the dose reduction was not seen to reduce tumor control probability.

On the quantification of the dosimetric accuracy of collapsed cone convolution superposition (CCCS) algorithm for small lung volumes using IMRT.

Specialized techniques that make use of small field dosimetry are common practice in today's clinics. These new techniques represent a big challenge to the treatment planning systems due to the lack of lateral electronic equilibrium. Because of this, the necessity of planning systems to overcome such difficulties and provide an accurate representation of the true value is of significant importance. Pinnacle3 is one such planning system. During the IMRT optimization process, Pinnacle3 treatment planning system allows the user to specify a minimum segment size which results in multiple beams composed of several subsets of different widths. In this study, the accuracy of the engine dose calculation, collapsed cone convolution superposition algorithm (CCCS) used by Pinnacle3, was quantified by Monte Carlo simulations, ionization chamber, and Kodak extended dose range film (EDR2) measurements for 11 SBRT lung patients. Lesions were < 3.0 cm in maximal diameter and <27.0cm3 in volume. The Monte Carlo EGSnrc\BEAMnrc and EGS4\MCSIM were used in the comparison. The minimum segment size allowable during optimization had a direct impact on the number of monitor units calculated for each beam. Plans with the smallest minimum segment size (0.1 cm2 to 2.0 cm2) had the largest number of MUs. Although PTV coverage remained unaffected, the segment size did have an effect on the dose to the organs at risk. Pinnacle3-calculated PTV mean doses were in agreement with Monte Carlo-calculated mean doses to within 5.6% for all plans. On average, the mean dose difference between Monte Carlo and Pinnacle3 for all 88 plans was 1.38%. The largest discrepancy in maximum dose was 5.8%, and was noted for one of the plans using a minimum segment size of 1.0 cm2. For minimum dose to the PTV, a maximum discrepancy between Monte Carlo and Pinnacle3 was noted of 12.5% for a plan using a 6.0 cm2 minimum segment size. Agreement between point dose measurements and Pinnacle3-calculated doses were on average within 0.7% in both phantoms. The profiles show a good agreement between Pinnacle3, Monte Carlo, and EDR2 film. The gamma index and the isodose lines support the result.