Multicenter Multivendor Evaluation of Dose Volume Histogram Creation Consistencies for 8 Commercial Radiation Therapy Dosimetric Systems.

PURPOSE: To evaluate dose volume histogram (DVH) construction differences across 8 major commercial treatment planning systems (TPS) and dose reporting systems for clinically treated plans of various anatomic sites and target sizes. METHODS AND MATERIALS: Dose files from 10 selected clinically treated plans with a hypofractionation, stereotactic radiation therapy prescription or sharp dose gradients such as head and neck plans ranging from prescription doses of 18 Gy in 1 fraction to 70 Gy in 35 fractions, each calculated at 0.25 and 0.125 cm grid size, were created and anonymized in Eclipse TPS, and exported to 7 other major TPS (Pinnacle, RayStation, and Elements) and dose reporting systems (MIM, Mobius, ProKnow, and Velocity) systems for comparison. Dose-volume constraint points of clinical importance for each plan were collected from each evaluated system (D0.03 cc [Gy], volume, and the mean dose were used for structures without specified constraints). Each reported constraint type and structure volume was normalized to the value from Eclipse for a pairwise comparison. A Wilcoxon rank-sum test was used for statistical significance and a multivariable regression model was evaluated adjusting for plan, grid size, and distance to target center. RESULTS: For all DVH points relative to Eclipse, all systems reported median values within 1.0% difference of each other; however, they were all different from Eclipse. Considering mean values, Pinnacle, RayStation, and Elements averaged at 1.038, 1.046, and 1.024, respectively, while MIM, Mobius, ProKnow, and Velocity reported 1.026, 1.050, 1.033, and 1.022, respectively relative to Eclipse. Smaller dose grid size improved agreement between the systems marginally without statistical significance. For structure volumes relative to Eclipse, larger differences are seen across all systems with a range in median values up to 3.0% difference and mean up to 10.1% difference. CONCLUSIONS: Large variations were observed between all systems. Eclipse generally reported, at statistically significant levels, lower values than all other evaluated systems. The nonsignificant change resulting from lowering the dose grid resolution indicates that this resolution may be less important than other aspects of calculating DVH curves, such as the 3-dimensional modeling of the structure.

Development and Dosimetric Characterization of a Customizable Shield for Subtotal Skin Electron Beam Therapy.

Purpose: Purpose: Subtotal skin electron beam therapy may be an option for patients with cutaneous lymphoma receiving radiation therapy to treat large areas of their skin but may benefit from sparing specific areas that may have had previous radiation therapy, are of specific cosmetic concern, and/or show no evidence of disease. We report here on the design, implementation, and dosimetric characteristics of a reusable and transparent customizable shield for use with the large fields used to deliver total skin electron beam therapy at extended distance with a conventional linear accelerator. Methods and Materials: A shield was designed and manufactured consisting of acrylic blocks that can be mounted on a steel frame to allow patient-specific shielding. The dosimetry of the device was measured using radiochromic film. Results: The shield is easy to use and well-tolerated for patient treatment, providing minimal electron transmission through the shield with a sharp penumbra at the field edge, with no increase in x-ray dose. We report on the dosimetry of a commercial device that has been used to treat more than 30 patients to date. Conclusions: The customizable shield is well suited to providing patient-specific shielding for subtotal skin electron beam therapy.

Technical note: Characterization of novel iterative reconstructed cone beam CT images for dose tracking and adaptive radiotherapy on L-shape linacs.

BACKGROUND: Cone-beam computed tomography (CBCT) allows for patient setup and positioning, and potentially dose verification or adaptive replanning prior to each treatment delivery. Poor CBCT image quality due to scatter artifacts and patient motion has been a major limiting factor. A new image reconstruction algorithm was recently clinically implemented for improving image quality through iterative reconstruction (iCBCT). PURPOSE: This study aims to characterize iCBCT image quality, establish image value (HU)-to-relative electron density (RED) calibration curves for dose calculation, and assess the dosimetric accuracy for different anatomical sites. MATERIAL AND METHODS: Both conventional CBCT and iCBCT scans were acquired from a Varian TrueBeam On-Board Imager system. A Catphan 604 phantom was scanned to compare image quality between the traditional Feldkamp-Davis-Kress (FDK) and novel iterative reconstruction techniques. Computerized Imaging Reference Systems (CIRS) electron density phantom was used to construct site-specific HU-RED curves corresponding to various scan settings. The CIRS Dynamic Thorax phantom, Rando pelvis phantom, and BrainLab head phantom were used for assessing dosimetric accuracy calculated on iCBCT images, compared to that on traditional FDK-based CBCT images. All phantoms were scanned on a computed tomography (CT) to obtain baseline HU values for comparison. RESULTS: Test results obtained from Catphan showed statistically significant improvement with iCBCT, compared to FDK CBCT. Average HU differences from the baseline CT values were improved to within ±30 HU for iCBCT, compared to FDK CBCT for phantom studies. Dose calculated on iCBCT for both phantoms and patient cases directly using baseline HU-RED calibration from CT showed 0.5%-2.0% accuracy from the baseline dose calculated on CT, which is comparable to doses calculated using site-specific HU-RED calibration curves. CONCLUSION: iCBCT provides improved image quality, improved HU accuracy compared to CT baseline, and has potential to provide online dose verification as part of the adaptive radiotherapy workflow directly using the baseline HU-RED calibration curve from CT.

Assessment of dose-volume histogram precision for five clinical systems.

PURPOSE: To investigate the dependency of dose-volume histogram (DVH) behavior and precision on underlying discretization using shapes and dose distributions with known analytical DVHs for five commercial DVH calculators. METHODS: DVHs and summary metrics were extracted from all five systems using synthetic cone and cylinder objects for which the true volume and DVH curves were known. Trends in the curves and metrics were explored by varying the underlying voxelization of the CT image, structure set, and dose grid as well by varying the geometry of the structure and direction of a linear dose gradient. Using synthetic structures allowed for comparison with ground truth DVH curves to assess their accuracy while an algorithm was additionally developed to assess the precision of each system. The precision was calculated with a novel algorithm that treats any "stair step" behavior in a DVH curve as an uncertainty band and calculates the width, characterized as a percent difference, of the band for various DVH metrics. The underlying voxelization was additionally changed and DVHs were extracted for two clinical examples. The details of how each system calculated DVHs were also investigated and tendencies in the calculated curves, metrics, and precision were related to choices made in the calculation methodology. RESULTS: Calculation methodology differences that had a noticeable impact on the DVH curves and summary metrics include supersampling beyond the input grids and interpretation of the superior and inferior ends of the structures. Among the systems studied, the median precision ranged from 0.902% to 3.22%, and interquartile ranges varied from 1.09% to 3.91%. CONCLUSIONS: Commercial dose-evaluation solutions can calculate different DVH curves, structure volume measures, and dose statistics for the same input data due to differences in their calculation methodologies. This study highlights the importance of understanding and investigating the DVH calculation when considering a new clinical system and when using more than one system for data transfer.

Comprehensive Commissioning and Clinical Implementation of GammaTiles STaRT for Intracranial Brain Cancer.

Purpose: To validate the dose calculation accuracy and dose distribution of GammaTiles for brain tumors, and to suggest a surgically targeted radiation therapy (STaRT) workflow for planning, delivery, radiation safety documentation, and posttreatment validation. Methods and Materials: Novel surgically targeted radiation therapy, GammaTiles, uses Cs-131 radiation isotopes embedded in collagen-based tiles that can be resorbed after surgery. GammaTile target delineation and dose calculation were performed on MIM Symphony software. Point-based and complex seed distribution calculations in MIM Symphony were verified with hand calculations and BrachyVision calculations. Vendor-provided 2-dimensional dose distribution calculation accuracy was validated using gafchromic EBT3 film measurements at various depths. A workflow was established for safe and effective GammaTile implants. Results: Good agreement was observed between different calculations. Calculation accuracy of less than 0.5% was achieved for all points except one, which had rounding issues for very low doses and resulted in just below 5% difference. Differences in anisotropy and geometry positioning were noticed in the delineation of Cs-131 IsoRay seeds in the compared systems, resulting in minor discrepancies in the calculated dosimetry distributions. Film measurements showed profiles with relatively good agreement of 0% to 5% in nongradient regions with higher differences between 5% to 10% in the sharp dose fall-off regions. Conclusions: A comprehensive evaluation of GammaTile geometry, dose distribution, and clinical workflow was conducted. Safe intro-operative implantation of GammaTiles requires extensive preplanning and interdisciplinary collaboration. A STaRT workflow was outlined to provide a guideline for an accurate treatment planning and safe implant process at other institutions.

GPU-accelerated Monte Carlo-based online adaptive proton therapy: A feasibility study.

PURPOSE: To develop an online graphic processing unit (GPU)-accelerated Monte Carlo-based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS. METHODS AND MATERIALS: A four-step workflow was developed using our in-house developed GPU-accelerated Monte Carlo-based treatment planning system to implement online Monte Carlo-based ART for PBS. The first step conducts diffeomorphic demon-based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two-stage (before and after delivery) patient-specific quality assurance (PSQA) of the reoptimized plan. The before-delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open-source Monte Carlo code, MCsquare. The after-delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS. RESULTS: For all three patients, the propagated contours were found to have good volume conformance [JI (lowest-highest: 0.833-0.983) and DSC (0.909-0.992)] but suboptimal boundary coincidence [HD (2.37-20.76 mm)] for organs-at-risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention. CONCLUSION: The proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients.

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2cm(3) for head and neck plans and brain plans and a contiguous volume of 5cm(3) for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.

Superresolution imaging of multiple fluorescent proteins with highly overlapping emission spectra in living cells.

Localization-based superresolution optical imaging is rapidly gaining popularity, yet limited availability of genetically encoded photoactivatable fluorescent probes with distinct emission spectra impedes simultaneous visualization of multiple molecular species in living cells. We introduce PAmKate, a monomeric photoactivatable far-red fluorescent protein, which facilitates simultaneous imaging of three photoactivatable proteins in mammalian cells using fluorescence photoactivation localization microscopy (FPALM). Successful probe identification was achieved by measuring the fluorescence emission intensity in two distinct spectral channels spanning only ~100 nm of the visible spectrum. Raft-, non-raft-, and cytoskeleton-associated proteins were simultaneously imaged in both live and fixed fibroblasts coexpressing Dendra2-hemagglutinin, PAmKate-transferrin receptor, and PAmCherry1-ß-actin fusion constructs, revealing correlations between the membrane proteins and membrane-associated actin structures.