Dose Matrices Research Articles

SU‐E‐T‐157: CARMEN: A MatLab‐Based Research Platform for Monte Carlo Treatment Planning (MCTP) and Customized System for Planning Evaluation

Purpose:Although there exist several radiotherapy research platforms, such as: CERR, the most widely used and referenced; SlicerRT, which allows treatment plan comparison from various sources; and MMCTP, a full MCTP system; it is still needed a full MCTP toolset that provides users complete control of calculation grids, interpolation methods and filters in order to “fairly” compare results from different TPSs, supporting verification with experimental measurements.Methods:This work presents CARMEN, a MatLab‐based platform including multicore and GPGPU accelerated functions for loading RT data; designing treatment plans; and evaluating dose matrices and experimental data.CARMEN supports anatomic and functional imaging in DICOM format, as well as RTSTRUCT, RTPLAN and RTDOSE. Besides, it contains numerous tools to accomplish the MCTP process, managing egs4phant and phase space files.CARMEN planning mode assist in designing IMRT, VMAT and MERT treatments via both inverse and direct optimization. The evaluation mode contains a comprehensive toolset (e.g. 2D/3D gamma evaluation, difference matrices, profiles, DVH, etc.) to compare datasets from commercial TPS, MC simulations (i.e. 3ddose) and radiochromic film in a user‐controlled manner.Results:CARMEN has been validated against commercial RTPs and well‐established evaluation tools, showing coherent behavior of its multiple algorithms. Furthermore, CARMEN platform has been used to generate competitive complex treatment that has been published in comparative studies.Conclusion:A new research oriented MCTP platform with a customized validation toolset has been presented. Despite of being coded with a high‐level programming language, CARMEN is agile due to the use of parallel algorithms. The wide‐spread use of MatLab provides straightforward access to CARMEN's algorithms to most researchers. Similarly, our platform can benefit from the MatLab community scientific developments as filters, registration algorithms etc. Finally, CARMEN arises the importance of grid and filtering control in treatment plan comparison.

SU-F-BRA-05: Utility of the Combined Use of Two Types of HDR Sources with the Direction Modulation Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer Treatment

Purpose: To maximize the dose to HRCTV while minimizing dose to the OARs, the combination of two HDR brachytherapy sources, 192-Ir and 169-Yb, used in combination with the recently-proposed novel direction modulated brachytherapy (DMBT) tandem applicator were examined. Methods: The DMBT tandem, made from nonmagnetic tungsten-alloy rod, with diameter of 5.4mm, has 6 symmetric peripheral holes of 1.3mm diameter. The 0.3mm thick bio-compatible plastic tubing wraps the tandem. MCNPX v.2.6 was used to simulate the mHDR 192-Ir V2 and 4140 HDR 169-Yb sources inside the DMBT applicator. Thought was by combining the higher energy 192-Ir (380keV) and lower energy 169-Yb (92.7keV) sources could create unprecedented level of dose conformality when combined with the high-degree intensity modulation capable DMBT tandem applicator. 3D dose matrices, with 1 mm3 resolution, were imported into an in-house-coded inverse optimization planning system to evaluate plan quality of 19 clinical patient cases. Prescription dose was 15Gy. All plans were normalized to receive the same HRCTV D90. Results: Generally, the use of dual sources produced better plans than using either of the sources alone, with significantly better performance in some patients. The mean D2cc for bladder, rectum, and sigmoid were 11.65±2.30Gy, 7.47±3.05Gy, and 9.84±2.48Gy for 192-Ir-only, respectively. For 169 -Yb-only, they were 11.67±2.26Gy, 7.44±3.02Gy, and 9.83±2.38Gy, respectively. The corresponding data for the dual sources were 11.51±2.24Gy, 7.30±3.00Gy, and 9.68 ±2.39Gy, respectively. The HRCTV D98 and V100 were 16.37±1.86Gy and 97.37±1.92Gy for Ir-192-only, respectively. For 169-Yb-only, they were 16.43±1.86Gy, and 97.51±1.91Gy, respectively. For the dual source, they were 16.42±1.87Gy and 97.47±1.93Gy, respectively. Conclusion: The plan quality improves, in some cases quite significantly, for when dual 192-Ir and 169-Yb sources are used in combination with highly intensity modulation capable DMBT tandem applicator for image guided cervical cancer brachytherapy.

Ir-192 HDR Source Parameter Validation Using Multichannel Gafchromic Film

Currently, Ir-192 HDR treatment planning system commissioning is only based on a single absolute measurement of source activity supplemented by validation of TG-43 parameters via dose point spot checks without independent verification that the planned distribution corresponds to the actual delivered dose. Reports in the literature indicate a need for more thorough tests to evaluate end-to-end accuracy of the treatment planning system. Gafchromic film has the potential for widespread clinical use to verify multiple source parameters due to its convenience for application without requiring a processor, excellent spatial resolution imperative in brachytherapy, and reported accuracy in external beam quality assurance. The purpose on this work is to present a methodology to validate the planned dose distribution for a single HDR dwell position as part of initial treatment planning commissioning and each source exchange to ensure that there are no unexpected changes in the source itself. The procedure presented independently calculates the one-dimensional dose perpendicular to the source, creates a robust calibration curve, and then compares a planned two-dimensional dose distribution with measured film dosimetry. A sheet of Gafchromic EBT3 film positioned in contact with a delivery catheter surrounded by water-equivalent scatter material is irradiated with an Ir-192 Nucletron HDR source. Dwell time is selected to be slightly below the film saturation density at the normalization point 5.0 mm from the source center. The film is digitized with an Epson 10000 XL color scanner. Film analysis is performed with MatLab imaging toolbox. Transmission values for the green channel, previously determined to have the greatest range and contrast, was converted into optical density (OD) as a function of perpendicular distance from the center of the calculated line source center. A corresponding theoretical dose curve was calculated using the TG43 formalism. The calculated dose in 0.1 mm increments was fitted to the measured OD in the 5-25 mm range to a sixth order polynomial. A comparable single source plan was created using the Oncentra treatment planning system. The 3D dose matrix was exported to a Varian Eclipse work station for convenient extraction of the 2D coronal dose plane with predetermined origin and scale at the level of the source for MatLab analysis. The Oncentra and measured film dose planes were registered at their corresponding origins as determined by lateral and vertical symmetry. The 2D dose matrices were individually scaled to 0.1 mm per pixel. The OD calibration curve consisting of 200 points was statistically valid, robust, and in agreement with Oncentra planned dose within +/- 1.5 % in the clinical range. A sixth order polynomial was necessary to accurately fit the film response throughout the usable film density range. Agreement between film and planned dose matrices was calculated at each corresponding position in the 2D dose plane as the absolute difference between the plan and measured doses. Areas near the source (5 mm lateral and 10 mm vertical to the source center) were excluded. Over 97% of the points had a dose agreement difference of less than 3% at exact corresponding points, which is an improvement over previously-published results using a gamma metric of 3% AND 3 mm. Figure below shows the agreement difference distribution. For clarity, only one side of the symmetrical image is displayed. The area within the white lines is the excluded region near the source. An accurate and robust calibration curve using the green channel of Gafchromic film can be easily created for use in validating HDR treatment planning systems. A single dwell position treatment plan verified with film dosimetry can serve to document the accuracy of all the theoretical model parameters. The methodology presented will be useful in implementing more comprehensive quality assurance on treatment planning systems and may even be extended in future work to verify patient-specific dose distributions.

First application of quantum annealing to IMRT beamlet intensity optimization

Optimization methods are critical to radiation therapy. A new technology, quantum annealing (QA), employs novel hardware and software techniques to address various discrete optimization problems in many fields. We report on the first application of quantum annealing to the process of beamlet intensity optimization for IMRT.We apply recently-developed hardware which natively exploits quantum mechanical effects for improved optimization. The new algorithm, called QA, is most similar to simulated annealing, but relies on natural processes to directly minimize a system’s free energy. A simple quantum system is slowly evolved into a classical system representing the objective function. If the evolution is sufficiently slow, there are probabilistic guarantees that a global minimum will be located.To apply QA to IMRT-type optimization, two prostate cases were considered. A reduced number of beamlets were employed, due to the current QA hardware limitations. The beamlet dose matrices were computed using CERR and an objective function was defined based on typical clinical constraints, including dose-volume objectives, which result in a complex non-convex search space. The objective function was discretized and the QA method was compared to two standard optimization methods, simulated annealing and Tabu search, run on a conventional computing cluster.Based on several runs, the average final objective function value achieved by the QA was 16.9 for the first patient, compared with 10.0 for Tabu and 6.7 for the simulated annealing (SA) method. For the second patient, the values were 70.7 for the QA, 120.0 for Tabu and 22.9 for the SA. The QA algorithm required 27–38% of the time required by the other two methods.In this first application of hardware-enabled QA to IMRT optimization, its performance is comparable to Tabu search, but less effective than the SA in terms of final objective function values. However, its speed was 3–4 times faster than the other two methods. This initial experiment suggests that more research into QA-based heuristics may offer significant speedup over conventional clinical optimization methods, as quantum annealing hardware scales to larger sizes.

Abstract A40: Synergism analysis of dose matrices for combinations of BKM120 (a PI3K inhibitor), MEK162 (a MEK1/2 inhibitor) and chemotherapy in colorectal cancer (CRC) cell lines

Abstract Aim: Most of targeted cancer drugs are developed in the clinical setting as single agent or as add-on of a standard treatment. Indeed, scarce data are available about the interaction effect in terms of synergism or antagonism for combinations of targeted agent or of targeted agents and cytotoxics at different doses. We studied the interaction effects of combinations of BKM120, MEK162 and SN38 (the active metabolite of irinotecan) on CRC cell lines. Materials and methods: A combination drug screening was performed on 7 CRC cell lines, 2 of which previously made resistant to irinotecan. For each cell line the combinations of BKM120 and MEK162, of BKM120 and SN38, and of MEK162 and SN38 were tested. Cell survival was assessed by sulforhodamine B cytotoxic assay in matrices of full-range dose combinations for both drugs. We compiled an R script to perform a synergy analysis according to a modified version of the method proposed by Léhar and al. (Nat Biotechnol 2009;27:659-666). Our version of the Léhar method allows quantification of synergism or antagonism for each dose combination point in dose matrices of two or more drugs, and yields a synthetic interaction parameter, the combination index (CI). A CI of > 0 indicating synergy, a CI of < 0 antagonism, and a CI of 0 additivity. Results: We could detect a pronounced synergism between BKM120 and MEK162, with a mean combination index of 1.82 for the 7 cell lines tested. Drug combinations including chemotherapy showed less positive interactions. A moderate synergistic interaction was detected between SN38 and MEK162, with a mean CI of 1.16. Combinations of SN38 and BKM120 were mainly additive, with a mean CI of 0.17. Interestingly, the distribution of synergistic effect was not homogeneous over the dose matrices. Analysis of matrices for the BKM120/MEK162 combination showed focal areas high synergy, which were quite constantly located in dose regions corresponding to IC10-IC30 for BKM120 and IC20-IC35 for MEK162. On the contrary, analysis of matrices for the BKM/SN38 combination showed focal areas of intense antagonism located in dose regions corresponding to IC15-IC30 for BKM120 and IC5-IC30 for SN38. No clear correlation was detected between, on the one side, the type of pharmacological interaction for all drug combinations tested and, on the other side, the mutational status of KRAS and p53, or sensitivity to irinotecan. Conclusions: Our data show the importance of an extensive preclinical testing of the interaction effects of drug combinations at different doses. We are now performing synergism analysis of three dimension matrices for three-drug combinations. Phosphoproteomic analysis of drug combination effect on this high synergism areas compared to other dose matrix areas is ongoing, with the aim to elucidate the underlying molecular mechanism(s). Citation Format: Diego Tosi, Salima Atis, Caroline Mollevi, Nadia Vie, Pierre Martineau, Celine Gongora. Synergism analysis of dose matrices for combinations of BKM120 (a PI3K inhibitor), MEK162 (a MEK1/2 inhibitor) and chemotherapy in colorectal cancer (CRC) cell lines. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A40.

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

Three dimensional dose verification of VMAT plans using the Octavius 4D dosimetric system

The Octavius 4D dosimetric system generates a 3D dose matrix based on a measured planar dose and user supplied Percentage Depth Dose (PDD) data. The accuracy of 3D dose matrices reconstructed by the Octavius 4D dosimetric system was systematically studied for an open static field, an open arc field and clinical VMAT plans. The Octavius reconstructed 3D dose matrices were compared with the Treatment Planning System (TPS) calculated 3D dose matrices using 3D gamma (γ) analysis with 2%/2mm and 3%/3mm tolerance criteria. The larger detector size in the 2D detector array of the Octavius system resulted in failed voxels in the high dose gradient regions. For the open arc fields mean (1σ) γ pass rates of 84.5(8.9) % and 94.2(4.5) % were observed with 2%/2mm and 3%/3mm tolerance criteria respectively and for clinical VMAT plans mean (1σ) γ pass rates of 86.8(3.5) % and 96.7(1.4) % were observed.

Abstract 3681: Synergism analysis of dose matrices for combinations of BKM120 (a PI3K inhibitor), MEK162 (a MEK1/2 inhibitor) and chemotherapy in colorectal cancer (CRC) cell lines

Abstract Most of targeted cancer drugs are developed in the clinical setting as single agent or as add-on of a standard treatment. Indeed, scarce data are available about the interaction effect in terms of synergism or antagonism for combinations of targeted agents or of targeted and cytotoxic agents at different doses. We studied the interaction effects of combinations of BKM120, MEK162 and SN38 (the active metabolite of irinotecan) on CRC cell lines. A combination drug screening was performed on 7 CRC cell lines, 2 of which previously made resistant to irinotecan. For each cell line the combinations of BKM120 and MEK162, of BKM120 and SN38, and of MEK162 and SN38 were tested. Cell survival was assessed by sulforhodamine B cytotoxic assay in matrices of full-range dose combinations for both drugs. We developed an R script to perform a synergy analysis according to a modified version of the method proposed by Léhar and al. (Nat Biotechnol 2009;27:659-666). This method of analysis allows quantification of synergism or antagonism for each dose combination point in dose matrices of two or more drugs, and yields a synthetic interaction parameter, the combination index (CI). A CI of > 0 indicating synergy, a CI of < 0 antagonism, and a CI of 0 additivity. We could detect a pronounced synergism between BKM120 and MEK162, with a mean combination index of 1.82 for the 7 cell lines tested. Drug combinations including chemotherapy showed less positive interactions. A moderate synergistic interaction was detected between SN38 and MEK162, with a mean CI of 1.16. Combinations of SN38 and BKM120 were mainly additive, with a mean CI of 0.17. Interestingly, the distribution of synergistic effect was not homogeneous over the dose matrices. Analysis of matrices for the BKM120/MEK162 combination showed focal areas with high synergy, which were quite always located in dose regions corresponding to IC10-IC30 for BKM120 and IC20-IC35 for MEK162. On the contrary, analysis of matrices for the BKM/SN38 combination showed focal areas of intense antagonism located in dose regions corresponding to IC15-IC30 for BKM120 and IC5-IC30 for SN38. No clear correlation was detected between, on the one side, the type of pharmacological interaction for all drug combinations tested and, on the other side, the mutational status of KRAS and p53, or sensitivity to irinotecan. Our data show the importance of an extensive preclinical testing of the interaction effects of drug combinations at different doses. We are now performing synergism analysis of three dimension matrices for three-drug combinations. Phosphoproteomic analysis of drug combination effect on this high synergism areas compared to other dose matrix areas is ongoing, with the aim of elucidating the underlying molecular mechanism(s). Citation Format: Diego Tosi, Salima Atis, Caroline Mollevi, Pierre Martineau, Céline Gongora. Synergism analysis of dose matrices for combinations of BKM120 (a PI3K inhibitor), MEK162 (a MEK1/2 inhibitor) and chemotherapy in colorectal cancer (CRC) cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3681. doi:10.1158/1538-7445.AM2014-3681

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution & superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to the 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.

SU-E-T-542: Comparison of Stereotactic Radiosurgery (SRS) of Brain Lesions Using Gamma Knife, VMAT, IMRT, and Conformal Arcs

Purpose: To compare dose distributions in stereotactic radiation surgery of brain lesions using gamma Knife, VMAT, conformal arcs, and IMRT in order to provide an optimal treatment. Methods: Dose distributions from single shot of 4C model of Gamma Knife at the helmet collimation sizes of 4, 8, 14, and 18 mm in diameter were compared with full arcs with the square shapes of 4×4 (or 5×5), 8×8 (or 10×10), and spherical shapes of 16 or 20 mm in diameter using EDR3 films in the same gamma knife QA phantom. Plans for ten SRS cases with single and multiple lesions were created in gamma knife plans and Pinnacle plans. The external beam plans had enlarged field size by 2-mm and used single conformal full circle arc for solitary lesion and none coplanar arcs/beams for multiple lesions. Coverage, conformity index, dose to critical organs, and integral dose to the brain and nearby critical structures were compared on all plans. Structures and dose matrices were registered in a Velocity deformable image registration system. Results: Single full circle arc from Elekta beam-modulate MLC (4-mm leaf thickness) and agility MLC (5-mm leaf thickness) have larger penumbra and less flatness than that of Gamma Knife singlemore » shot. None-coplanar arcs or beams were required to achieve similar dose distribution. In general, Gamma Knife plans provided significant less integral dose than that of linac-based plans. Benefits of IMRT and VMAT versus gamma Knife and conformal arcs were not significant. Conclusion: Our dose measurement and treatment planning evaluation clearly demonstrated dose distribution differences amount current popular SRS modalities for small solitary and multiple brain lesions. The trend of using MLC shape beams or arcs to replace conventional cones should be revisited in order to keep lower integral dose if the late correlates with some radiation-induced side effects. Pilot grant from Elekta LLC.« less

SU-E-T-532: Validation and Implementation of Model-Based Patient Specific Quality Assurance Using Mobius3D and MobiusFX in a Clinical Setting

Purpose: This work carries out the commissioning and validation of the Mobius3D and MobiusFX software tools, which can replace the time-consuming measurement-based patient specific quality assurance (PSQA). Methods: The beam model supplied by Mobius3D was validated against a 21EX linac's beam measured data. Complex patient (VMAT) plans using Eclipse treatment planning system (TPS) was used to test the consistency between Mobius3D (calculates dose using patient image and field data) and MobiusFx (calculates dose using treatment dynalog files). Dose difference and gamma analysis (3%/3mm) between Mobius3D and MobiusFx were used to assess treatment plan and treatment delivery consistency. An end-to-end test was performed to validate Mobius3D and MobiusFx against ion chamber measurements. Effect of the dosimetric leaf gap (DLG) on Mobius3D dose calculation was additionally investigated. Results: Mobius3D beam model parameters matched within 1%-3% with our beam measured data. A comparison of Mobius3D and MobiusFx dose matrices for VMAT planned prostate cases showed (0.33±0.07)% mean dose difference with gamma values above 95%. The end-to-end test showed dose differences of 1% between Mobius3D and MobiusFx. Dependence of Mobius3D dose calculation upon DLG was explored by introducing a ±0.5 mm change in the default value for DLG. This change resulted in agreement differences above 2% Conclusion: Use of reference beam data would appear to speed up commissioning process for the clinical implementation of Mobius3D. However, careful consideration is required when comparing the information provided by the software, since large dose variations can be seen when the proper parameters are not optimized. The plan and delivered dose were in good agreement; hence MobiusFx has the potential to significantly speed up the PSQA process and at the same time helps to verify treatment parameters that are not possible with measurement-based PSQA.

SU‐E‐T‐490: Clinical Analysis of the Approximate Multi‐Phase Biological Effective Dose (BED) Calculation

Purpose:An approximate, multi‐phase biological effective dose (BED) equation was introduced to simplify 3D‐BED calculations by treatment planning systems. The purpose of this work is to analyze its clinical accuracy within patients receiving two phase treatments (e.g., primary and boost phases).Methods:Twenty prostate and brain cancer patients were studied. MATLAB was used to calculate the true‐BED (BEDT) and approximate‐BED (BEDA), on a voxel‐basis within both phases, using the physical dose matrices that were exported from Pinnacle3 (Philips Medical, Fitchburg, WI). The data was analyzed using the percent error equation of BEDA with respect to BEDT. The Bland‐Altman Analysis and the Pearson's Correlation Coefficient were also used in order to study the impact of the dose distributions on the accuracy of BEDA.Results:It was shown that when the dose‐per‐fractions (DPF) between both phases were equal, the error was zero. Within brain cancer patients, 50 percent of the Optic Chiasms and Brainstems, 60–70 percent of the Left and Right Optic Nerves, and 80 percent of the Normal Brain and Spinal Cord had a BEDA with less than a 1 percent error. For prostate cancer patients, 60–70 percent of the Rectum and Bladder also had a BEDA with less than a 1 percent error. The BA‐Analysis and PCC also revealed the significant impact of the dose distribution and the locations of the OAR and target on the accuracy of BEDA.Conclusion:The results displayed accurate BEDA calculations in certain cases such as the Normal Brain, yet patients with large errors still existed. Due to the imprecision of BEDA on OARs, and the difficulty in predicting when it would be accurate, we recommend using BEDA only for targets due to a greater probability of seeing equivalent DPF values in both phases because of the homogeneous dose distributions delivered to the target volumes.

SU‐E‐T‐480: Radiobiological Dose Comparison of Single Fraction SRS, Multi‐Fraction SRT and Multi‐Stage SRS of Large Target Volumes Using the Linear‐Quadratic Formula

Purpose:To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi‐fractionated SRT, and multi‐staged SRS treatment.Methods:An anthropomorphic head phantom with a centrally located large volume target (18.2 cm3) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue.Results:Singe fraction SRS, multi‐stage plan and multi‐fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively.Conclusion:The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi‐stage treatment provided for a more potent biologically effect on target compared to the multi‐fraction SRT treatments with less biological normal tissue than single‐fraction SRS treatment.

IMRT credentialing for prospective trials using institutional virtual phantoms: results of a joint European Organization for the Research and Treatment of Cancer and Radiological Physics Center project.

Background and purposeIntensity-modulated radiotherapy (IMRT) credentialing for a EORTC study was performed using an anthropomorphic head phantom from the Radiological Physics Center (RPC; RPCPH). Institutions were retrospectively requested to irradiate their institutional phantom (INSTPH) using the same treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT credentialing.Materials and methodsCT data set of the institutional phantom and measured 2D dose matrices were requested from centers and sent to a dedicated secure EORTC uploader. Data from the RPCPH and INSTPH were thereafter centrally analyzed and inter-compared by the QA team using commercially available software (RIT; ver.5.2; Colorado Springs, USA).ResultsEighteen institutions participated to the VPP. The measurements of 6 (33%) institutions could not be analyzed centrally. All other centers passed both the VPP and the RPC ±7%/4 mm credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing), 11(92%) as compared to 12 (100%) centers pass the credentialing process with RPCPH and INSTPH (p = 0.29), respectively. The corresponding pass rate for the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p = 0.01), respectively.ConclusionsIMRT dosimetry gamma evaluations in a single plane for a H&N prospective trial using the INSTPH measurements showed agreement at the gamma index criteria of ±5%/5 mm (90% of pixels passing) for a small number of VPP measurements. Using more stringent, criteria, the RPCPH and INSTPH comparison showed disagreement. More data is warranted and urgently required within the framework of prospective studies.

SU‐E‐J‐154: Deformable Image Registration Based Delivered Dose Estimation for Head and Neck Radiotherapy

Purpose:To estimate the accumulated dose to targets and organs at risk (OAR) for head and neck (H' N) radiotherapy using 3 deformable image registration (DIR) algorithms.Methods:Five H' N patients, who had daily CBCTs taken during the course of treatment, were retrospectively studied. All plans had 5 mm CTV‐to‐PTV expansions. To overcome the small field of view (FOV) limitations and HU uncertainties of CBCTs, CT images were deformably registered using a parameter‐optimized B‐spline DIR algorithm (Elastix, elastix.isi.uu.nl) and resampled onto each CBCT with a 4 cm uniform FOV expansion. The dose of the day was calculated on these resampled CT images. Calculated daily dose matrices were warped and accumulated to the planning CT using 3 DIR algorithms; SmartAdapt (Eclipse/Varian), Velocity (Velocity Medical Solutions), and Elastix. Dosimetric indices for targets and OARs were determined from the DVHs and compared with corresponding planned quantities.Results:The cumulative dose deviation was less than 2%, on average, for PTVs from the corresponding plan dose, for all algorithms/patients. However, the parotids show as much as a 37% deviation from the intended dose, possibly due to significant patient weight loss during the first 3 weeks of treatment (15.3 lbs in this case). The mean(±SD) cumulative dose deviations of the 5 patients estimated using the 3 algorithms (SmartAdapt, Velocity, and Elastix) were (0.8±0.9%, 0.5±0.9%, 0.6±1.3%) for PTVs, (1.6±1.9%, 1.4±2.0%, 1.7±1.9%) for GTVs, (10.4±12.1%, 10.7±10.6%, 6.5±10.1%) for parotid glands, and (4.5±4.6%, 3.4±5.7%, 3.9±5.7%) for mucosa, respectively. The differences among the three DIR algorithms in the estimated cumulative mean doses (1SD (in Gy)) were: 0.1 for PTVs, 0.1 for GTVs, 1.9 for parotid glands, and 0.4 for mucosa.Conclusion:Results of this study are suggestive that more frequent plan adaptation for organs, such as the parotid glands, might be beneficial during the course of H' N RT.This study was supported in part by a research grant from Varian Medical Systems, Palo Alto, CA

SU‐E‐T‐514: Simultaneously Determination of Radiation Isocentricity of Gantry, Collimator and Couch Using a Commercial Three‐Dimensional Dosimetry QA Apparatus

Purpose:Radiation isocentricity is an important benchmark for a LINAC and is typically determined by 3 separate film star‐shots. We developed a technique to simultaneously determine the radiation isocenter of gantry, collimator and couch with a commercial 3D QA apparatus.Methods:The ArcCHECK from SunNuclear was used on two LINACs. It was aligned with room lasers. For gantry rotation, collimator and couch were set to zero and gantry was placed to 0, 49, 213 and 311 degrees. Similarly, a set of collimator/couch angles were chosen with the other two axes at neutral positions. The measured dose matrices were analyzed by an in‐house MATLAB program. For each shot, the central axis was determined by computing the FWHM of the diode arrays. The largest inscribed circle from these central axis lines was used to determine isocenter: the radius as the benchmark of isocentricity and the coordinates of the center as the discrepancy of radiation isocenter to the origin defined by lasers. To validate the method, the couch was shifted by ~5 mm in all three directions and measurements were repeated.Results:The radius of the largest inscribed circle for gantry, collimator and couch are (0.3, 0.5, 0.2) mm for one LINAC and (0.2, 0.3, 0.1) mm for the other, in agreement with the film star‐shots at annual QA. The discrepancies of radiation isocenter are generally within 1 mm, except gantry rotation on one LINAC due to the drift of foot laser. The differences in positions detected are consistent with the intentional predefined shift.Conclusion:We have demonstrated a technique for the simultaneous measurement of gantry, collimator, and couch isocentricity with a set of carefully chosen irradiation parameters based on the specific construction geometry of the 3D detector ArcCheck. This can replace the standard film star‐shots. The future work includes improving operation efficiency.

SU‐F‐BRD‐13: Quantum Annealing Applied to IMRT Beamlet Intensity Optimization

Purpose:We report on the first application of quantum annealing (QA) to the process of beamlet intensity optimization for IMRT. QA is a new technology, which employs novel hardware and software techniques to address various discrete optimization problems in many fields.Methods:We apply the D‐Wave Inc. proprietary hardware, which natively exploits quantum mechanical effects for improved optimization. The new QA algorithm, running on this hardware, is most similar to simulated annealing, but relies on natural processes to directly minimize the free energy of a system. A simple quantum system is slowly evolved into a classical system, representing the objective function. To apply QA to IMRT‐type optimization, two prostate cases were considered. A reduced number of beamlets were employed, due to the current QA hardware limitation of ∼500 binary variables. The beamlet dose matrices were computed using CERR, and an objective function was defined based on typical clinical constraints, including dose‐volume objectives. The objective function was discretized, and the QA method was compared to two standard optimization Methods: simulated annealing and Tabu search, run on a conventional computing cluster.Results:Based on several runs, the average final objective function value achieved by the QA was 16.9 for the first patient, compared with 10.0 for Tabu and 6.7 for the SA. For the second patient, the values were 70.7 for the QA, 120.0 for Tabu, and 22.9 for the SA. The QA algorithm required 27–38% of the time required by the other two methods.Conclusion:In terms of objective function value, the QA performance was similar to Tabu but less effective than the SA. However, its speed was 3–4 times faster than the other two methods. This initial experiment suggests that QA‐based heuristics may offer significant speedup over conventional clinical optimization methods, as quantum annealing hardware scales to larger sizes.

Pre-treatment radiotherapy dose verification using Monte Carlo doselet modulation in a spherical phantom

Due to the increasing complexity of radiotherapy delivery, accurate dose verification has become an essential part of the clinical treatment process. The purpose of this work was to develop a pre-treatment verification technique capable of quickly reconstructing 3D dose distributions from both coplanar and non-coplanar treatments. For each treatment field, electronic portal images were taken in non-transmission mode (with no patient in the beam) allowing the derivation of the delivered fluence maps. The dose reconstruction was then performed in a spherical water phantom by modulating and summing the Monte Carlo (MC) doselets, defined on a spherical co-ordinate system, and pre-calculated from azimuthally symmetric fluence above the jaws. The technique, called the spherical doselet modulation (SDM) method, essentially eliminates the statistical uncertainty of the MC dose calculations by exploiting the azimuthal symmetry in both a patient-independent phase-space and in a virtual spherical water phantom. For example, this symmetry allowed the number of doselets necessary for dose reconstruction to be reduced by a factor of ∼250. In this work, only 51 radially binned doselets were used (each generated from all particles in a given annulus of the phase-space, azimuthally redistributed into a small cylindrical sector). The SDM method mitigates the most computationally intensive part of this type of dose reconstruction-–reading, weighting and summing dose matrices. The accuracy of the system was tested against MC calculations as well as our previously reported phase-space modulation method, using a series of open field and IMRT cases. The mean chi- and gamma-test 3%/3 mm success rates of the SDM method were 98.6% and 99.5%, respectively, when compared to full MC simulation. The total calculation time was 96 s per treatment field on a single processor core.

Deformable Image Registration Accuracy in the Head and Neck Region: Comparison With Interobserver Variation

Deformable Image Registration Accuracy in the Head and Neck Region: Comparison With Interobserver Variation

A novel technique for VMAT QA with EPID in cine mode on a Varian TrueBeam linac

Volumetric modulated arc therapy (VMAT) is a relatively new treatment modality for dynamic photon radiation therapy. Pre-treatment quality assurance (QA) is necessary and many efforts have been made to apply electronic portal imaging device (EPID)-based IMRT QA methods to VMAT. It is important to verify the gantry rotation speed during delivery as this is a new variable that is also modulated in VMAT. In this paper, we present a new technique to perform VMAT QA using an EPID. The method utilizes EPID cine mode and was tested on Varian TrueBeam in research mode. The cine images were acquired during delivery and converted to dose matrices after profile correction and dose calibration. A sub-arc corresponding to each cine image was extracted from the original plan and its portal image prediction was calculated. Several analyses were performed including 3D γ analysis (2D images + gantry angle axis), 2D γ analysis, and other statistical analyses. The method was applied to 21 VMAT photon plans of 3 photon energies. The accuracy of the cine image information was investigated. Furthermore, this method's sensitivity to machine delivery errors was studied. The pass rate (92.8 ± 1.4%) for 3D γ analysis was comparable to those from Delta4 system (99.9 ± 0.1%) under similar criteria (3%, 3 mm, 5% threshold and 2° angle to agreement) at 6 MV. The recorded gantry angle and start/stop MUs were found to have sufficient accuracy for clinical QA. Machine delivery errors can be detected through combined analyses of 3D γ, gantry angle, and percentage dose difference. In summary, we have developed and validated a QA technique that can simultaneously verify the gantry angle and delivered MLC fluence for VMAT treatment.This technique is efficient and its accuracy is comparable to other QA methods.