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DOE OSTI2014

WE-G-16A-01: Evolution of Radiation Treatment Planning

Welcome and Introduction - Lawrence N. Rothenberg This symposium is one a continuing series of presentations at AAPM Annual Meetings on the historical aspects of medical physics, radiology, and radiation oncology that have been organized by the AAPM History Committee. Information on previous presentations including “Early Developments in Teletherapy” (Indianapolis 2013), “Historical Aspects of Cross-Sectional Imaging” (Charlotte 2012), “Historical Aspects of Brachytherapy” (Vancouver 2011), “50 Years of Women in Medical Physics” (Houston 2008), and “Roentgen's Early Investigations” (Minneapolis 2007) can be found in the Education Section of the AAPM Website. The Austin 2014 History Symposium will be on “Evolution of Radiation Treatment Planning.” Overview - Radhe Mohan Treatment planning is one of the most critical components in the chain of radiation therapy of cancers. Treatment plans of today contain a wide variety of sophisticated information conveying the potential clinical effectiveness of the designed treatment to practitioners. Examples of such information include dose distributions superimposed on three- or even four-dimensional anatomic images; dose volume histograms, dose, dose-volume and dose-response indices for anatomic structures of interest; etc. These data are used for evaluating treatment plans and for making treatment decisions. The current state-of-the-art has evolved from the 1940s era when the dose to the tumor and normal tissues was estimated approximately by manual means. However, the symposium will cover the history of the field from the late-1950's, when computers were first introduced for treatment planning, to the present state involving the use of high performance computing and advanced multi-dimensional anatomic, functional and biological imaging, focusing only on external beam treatment planning. The symposium will start with a general overview of the treatment planning process including imaging, structure delineation, assignment of dose requirements, consideration of uncertainties, selection of beam configurations and shaping of beams, and calculations, optimization and evaluation of dose distributions. This will be followed by three presentations covering the evolution of treatment planning, which parallels the evolution of computers, availability of advanced volumetric imaging and the development of novel technologies such as dynamic multi-leaf collimators and online image guidance. This evolution will be divided over three distinct periods - prior to 1970's, the 2D era; from 1980 to the mid-1990's, the 3D era; and from the mid 1990's to today, the IMRT era. When the World was Flat: The Two-Dimensional Radiation Therapy Era” - Jacob Van Dyk In the 2D era, anatomy was defined with the aid of solder wires, special contouring devices and projection x-rays. Dose distributions were calculated manually from single field, flat surface isodoses on transparencies. Precalculated atlases of generic dose distributions were produced by the International Atomic Energy Agency. Massive time-shared main frames and mini-computers were used to compute doses at individual points or dose distributions in a single plane. Beam shapes were generally rectangular, with wedges, missing tissue compensators and occasional blocks to shield critical structures. Dose calculations were measurement-based or they used primary and scatter calculations based on scatter-air ratio methodologies. Dose distributions were displayed on line printers as alpha-numeric character maps or isodose patterns made with pen plotters. More than Pretty Pictures: 3D Treatment Planning and Conformal Therapy - Benedick A. Fraass The introduction of computed tomography allowed the delineation of anatomy three-dimensionally and, supported partly by contracts from the National Cancer Institute, made possible the introduction and clinical use of 3D treatment planning, leading to development and use of 3D conformal therapy in the 1980's. 3D computer graphics and 3D anatomical structure definitions made possible Beam's Eye View (BEV) displays, making conformal beam shaping and much more sophisticated beam arrangements possible. These conformal plans significantly improved target dose coverage as well as normal tissue sparing. The use of dose volume histograms, gross/clinical/planning target volumes, MRI and PET imaging, multileaf collimators, and computer-controlled treatment delivery made sophisticated planning approaches practical. The significant improvements in dose distributions and analysis achievable with 3D conformal therapy made possible formal dose escalation and normal tissue tolerance clinical studies that set new and improved expectations for improved local control and decreasing complications in many clinical sites. From the Art to the State of the Art: Inverse Planning and IMRT - Thomas R. Bortfeld While the potential of intensity modulation was recognized in the mid- 1980's, intensity-modulated radiotherapy (IMRT) did not become a reality until the mid-1990's. Broad beams of photons could be sub-divided into narrow beamlets whose intensities could be determined using sophisticated optimization algorithms to appropriately balance tumor dose with normal tissue sparing. The development of dynamic multi-leaf collimators (on conventional linear accelerators as well as in helical delivery devices) enabled the efficient delivery of IMRT. The evolution of IMRT planning is continuing in the form of Volumetric Modulated Arc Therapy (VMAT) and through advanced optimization tools, such as multi-criteria optimization, automated IMRT planning, and robust optimization to protect dose distributions against uncertainties. IMRT also facilitates “dose painting” in which different sub-volumes of the target are prescribed different doses. Clearly, these advancements are being made possible by the increasing power and lower cost of computers and developments in other fields such as imaging and operations research. Summary - Radhe Mohan The history does not end here. The advancement of treatment planning is expected to continue, leading to further automation and improvements in conformality and robustness of dose distributions, particularly in the area of particle therapy. Radiobiological modeling will gain emphasis as part of the planning process. Learning Objectives: The scope of changes in technology and the capabilities of radiation treatment planning The impact of these changes in the quality of treatment plans and optimality of dose distributions The impact of development in other fields (imaging, computers, operations research, etc.) on the evolution of radiation treatment planning.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Effect of dosimeter type for commissioning small photon beams on calculated dose distribution in stereotactic radiosurgery

Purpose: To assess the impact of the detector used to commission small photon beams on the calculated dose distribution in stereotactic radiosurgery (SRS). Methods: In this study, six types of detectors were used to characterize small photon beams: three diodes [a silicon stereotactic field diode SFD, a silicon diode SRS, and a silicon diode E], an ionization chamber CC01, and two types of radiochromic film models EBT and EBT2. These detectors were used to characterize circular collimated beams that were generated by a Novalis linear accelerator. This study was conducted in two parts. First, the following dosimetric data, which are of particular interest in SRS, were compared for the different detectors: the total scatter factor (TSF), the tissue phantom ratios (TPRs), and the off-axis ratios (OARs). Second, the commissioned data sets were incorporated into the treatment planning system (TPS) to compare the calculated dose distributions and the dose volume histograms (DVHs) that were obtained using the different detectors. Results: The TSFs data measured by all of the detectors were in good agreement with each other within the respective statistical uncertainties: two exceptions, where the data were systematically below those obtained for the other detectors, were the CC01 results for all of the circular collimators and the EBT2 film results for circular collimators with diameters below 10.0 mm. The OAR results obtained for all of the detectors were in excellent agreement for all of the circular collimators. This observation was supported by the gamma-index test. The largest difference in the TPR data was found for the 4.0 mm circular collimator, followed by the 10.0 and 20.0 mm circular collimators. The results for the calculated dose distributions showed that all of the detectors passed the gamma-index test at 100% for the 3 mm/3% criteria. The aforementioned observation was true regardless of the size of the calculation grid for all of the circular collimators. Finally, the dose volume histogram results were independent of the size of the calculation grid used. Conclusions: The results of this study showed that all of the studied detectors produced similar commissioned data sets for the TPS dose calculations. However, this result only validated the dose distribution calculation in the TPS and could not be used to assess the dose delivery to the target in which the TFS data were used to calculate the monitor units (the TFS data were not used in the TPS dose distribution calculation). Therefore, this study could not be used to determine the most accurate detector commissioning data set; however, all of the detectors exhibited superior performance for the relative dosimetry of small photon beams.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2014

Assessing and accounting for the impact of respiratory motion on FDG uptake and viable volume for liver lesions in free-breathing PET using respiration-suspended PET images as reference

Purpose: To assess and account for the impact of respiratory motion on the variability of activity and volume determination of liver tumor in positron emission tomography (PET) through a comparison between free-breathing (FB) and respiration-suspended (RS) PET images. Methods: As part of a PET/computed tomography (CT) guided percutaneous liver ablation procedure performed on a PET/CT scanner, a patient's breathing is suspended on a ventilator, allowing the acquisition of a near-motionless PET and CT reference images of the liver. In this study, baseline RS and FB PET/CT images of 20 patients undergoing thermal ablation were acquired. The RS PET provides near-motionless reference in a human study, and thereby allows a quantitative evaluation of the effect of respiratory motion on PET images obtained under FB conditions. Two methods were applied to calculate tumor activity and volume: (1) threshold-based segmentation (TBS), estimating the total lesion glycolysis (TLG) and the segmented volume and (2) histogram-based estimation (HBE), yielding the background-subtracted lesion (BSL) activity and associated volume. The TBS method employs 50% of the maximum standardized uptake value (SUV{sub max}) as the threshold for tumors with SUV{sub max} ≥ 2× SUV{sub liver-bkg}, and tumor activity above this threshold yields TLG{sub 50%}. The HBE method determines local PET background based on a Gaussian fit of the low SUV peak in a SUV-volume histogram, which is generated within a user-defined and optimized volume of interest containing both local background and lesion uptakes. Voxels with PET intensity above the fitted background were considered to have originated from the tumor and used to calculate the BSL activity and its associated lesion volume. Results: Respiratory motion caused SUV{sub max} to decrease from RS to FB by −15% ± 11% (p = 0.01). Using TBS method, there was also a decrease in SUV{sub mean} (−18% ± 9%, p = 0.01), but an increase in TLG{sub 50%} (18% ± 36%) and in the segmented volume (47% ± 52%, p = 0.01) from RS to FB PET images. The background uptake in normal liver was stable, 1% ± 9%. In contrast, using the HBE method, the differences in both BSL activity and BSL volume from RS to FB were −8% ± 10% (p = 0.005) and 0% ± 16% (p = 0.94), respectively. Conclusions: This is the first time that almost motion-free PET images of the human liver were acquired and compared to free-breathing PET. The BSL method's results are more consistent, for the calculation of both tumor activity and volume in RS and FB PET images, than those using conventional TBS. This suggests that the BSL method might be less sensitive to motion blurring and provides an improved estimation of tumor activity and volume in the presence of respiratory motion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

A novel approach for evaluation of prostate deformation and associated dosimetric implications in IGRT of the prostate

Purpose: Prostate deformation is assumed to be a secondary correction and is typically ignored in the planning target volume (PTV) margin calculations. This assumption needs to be tested, especially when planning margins are reduced with daily image-guidance. In this study, deformation characteristics of the prostate and seminal vesicles were determined, and the dosimetric impact on treatment plans with different PTV margins was investigated. Methods: Ten prostate cancer patients were retrospectively selected for the study, each with three fiducial markers implanted in the prostate. Two hundred CBCT images were registered to respective planning CT images using a B-spline-based deformable image registration (DIR) software. A manual bony anatomy-based match was first applied based on the alignment of the pelvic bones and fiducial landmarks. DIR was then performed. For each registration, deformation vector fields (DVFs) of the prostate and seminal vesicles (SVs) were quantified using deformation-volume histograms. In addition, prostate rotation was evaluated and compared with prostate deformation. For a patient demonstrating small and large prostate deformations, target coverage degradation was analyzed in each of three treatment plans with PTV margins of 10 mm (6 mm at the prostate/rectum interface), as well as 5, and 3 mm uniformly. Results: Deformation of the prostate was most significant in the anterior direction. Maximum prostate deformation of greater than 10, 5, and 3 mm occurred in 1%, 17%, and 76% of the cases, respectively. Based on DVF-histograms, DVF magnitudes greater than 5 and 3 mm occurred in 2% and 27% of the cases, respectively. Deformation of the SVs was most significant in the posterior direction, and it was greater than 5 and 3 mm in 7.5% and 44.9% of the cases, respectively. Prostate deformation was found to be poorly correlated with rotation. Fifty percent of the cases showed rotation with negligible deformation and 7% of the cases showed significant deformation with minimal rotation (<3°). Average differences in the D{sub 95} dose to the prostate + SVs between the planning CT and CBCT images was 0.4% ± 0.5%, 3.0% ± 2.8%, and 6.6% ± 6.1%, respectively, for the plans with 10/6, 5, and 3 mm margins. For the case with both a large degree of prostate deformation (≈10% of the prostate volume) and rotation (≈8°), D{sub 95} was reduced by 0.5% ± 0.1%, 6.8% ± 0.6%, and 20.9% ± 1.6% for 10/6, 5, and 3 mm margin plans, respectively. For the case with large prostate deformation but negligible rotation (<1°), D{sub 95} was reduced by 0.4 ± 0.3, 3.9 ± 1.0, and 11.5 ± 2.5 for 10/6, 5, and 3 mm margin plans, respectively. Conclusions: Prostate deformation over a course of fractionated prostate radiotherapy may not be insignificant and may need to be accounted for in the planning margin design. A consequence of these results is that use of highly reduced planning margins must be viewed with caution.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Poster — Thur Eve — 69: Computational Study of DVH-guided Cancer Treatment Planning Optimization Methods

Purpose: To compare methods to incorporate the Dose Volume Histogram (DVH) curves into the treatment planning optimization. Method: The performance of three methods, namely, the conventional Mixed Integer Programming (MIP) model, a convex moment-based constrained optimization approach, and an unconstrained convex moment-based penalty approach, is compared using anonymized data of a prostate cancer patient. Three plans we generated using the corresponding optimization models. Four Organs at Risk (OARs) and one Tumor were involved in the treatment planning. The OARs and Tumor were discretized into total of 50,221 voxels. The number of beamlets was 943. We used commercially available optimization software Gurobi and Matlab to solve the models. Plan comparison was done by recording the model runtime followed by visual inspection of the resulting dose volume histograms. Conclusion: We demonstrate the effectiveness of the moment-based approaches to replicate the set of prescribed DVH curves. The unconstrained convex moment-based penalty approach is concluded to have the greatest potential to reduce the computational effort and holds a promise of substantial computational speed up.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Toward adaptive radiotherapy for head and neck patients: Uncertainties in dose warping due to the choice of deformable registration algorithm

Purpose: The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping. Methods: The authors describe a DIR based adaptive radiotherapy workflow, using CT and cone-beam CT (CBCT) imaging. The transformations that mapped the anatomy between the two time points were obtained using four different DIR approaches available in NiftyReg. These included a standard unidirectional algorithm and more sophisticated bidirectional ones that encourage or ensure inverse consistency. The forward (CT-to-CBCT) deformation vector fields (DVFs) were used to propagate the CT Hounsfield units and structures to the daily geometry for “dose of the day” calculations, while the backward (CBCT-to-CT) DVFs were used to remap the dose of the day onto the planning CT (pCT). Data from five head and neck patients were used to evaluate the performance of each implementation based on geometrical matching, physical properties of the DVFs, and similarity between warped dose distributions. Geometrical matching was verified in terms of dice similarity coefficient (DSC), distance transform, false positives, and false negatives. The physical properties of the DVFs were assessed calculating the harmonic energy, determinant of the Jacobian, and inverse consistency error of the transformations. Dose distributions were displayed on the pCT dose space and compared using dose difference (DD), distance to dose difference, and dose volume histograms. Results: All the DIR algorithms gave similar results in terms of geometrical matching, with an average DSC of 0.85 ± 0.08, but the underlying properties of the DVFs varied in terms of smoothness and inverse consistency. When comparing the doses warped by different algorithms, we found a root mean square DD of 1.9% ± 0.8% of the prescribed dose (pD) and that an average of 9% ± 4% of voxels within the treated volume failed a 2%pD DD-test (DD{sub 2%-pp}). Larger DD{sub 2%-pp} was found within the high dose gradient (21% ± 6%) and regions where the CBCT quality was poorer (28% ± 9%). The differences when estimating the mean and maximum dose delivered to organs-at-risk were up to 2.0%pD and 2.8%pD, respectively. Conclusions: The authors evaluated several DIR algorithms for CT-to-CBCT registrations. In spite of all methods resulting in comparable geometrical matching, the choice of DIR implementation leads to uncertainties in dose warped, particularly in regions of high gradient and/or poor imaging quality.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Methods, software and datasets to verify DVH calculations against analytical values: Twenty years late(r)

Purpose: The authors designed data, methods, and metrics that can serve as a standard, independent of any software package, to evaluate dose-volume histogram (DVH) calculation accuracy and detect limitations. The authors use simple geometrical objects at different orientations combined with dose grids of varying spatial resolution with linear 1D dose gradients; when combined, ground truth DVH curves can be calculated analytically in closed form to serve as the absolute standards. Methods: DICOM RT structure sets containing a small sphere, cylinder, and cone were created programmatically with axial plane spacing varying from 0.2 to 3 mm. Cylinders and cones were modeled in two different orientations with respect to the IEC 1217 Y axis. The contours were designed to stringently but methodically test voxelation methods required for DVH. Synthetic RT dose files were generated with 1D linear dose gradient and with grid resolution varying from 0.4 to 3 mm. Two commercial DVH algorithms—PINNACLE (Philips Radiation Oncology Systems) and PlanIQ (Sun Nuclear Corp.)—were tested against analytical values using custom, noncommercial analysis software. In Test 1, axial contour spacing was constant at 0.2 mm while dose grid resolution varied. In Tests 2 and 3, the dose grid resolution was matched to varying subsampled axial contours with spacing of 1, 2, and 3 mm, and difference analysis and metrics were employed: (1) histograms of the accuracy of various DVH parameters (total volume, D{sub max}, D{sub min}, and doses to % volume: D99, D95, D5, D1, D0.03 cm{sup 3}) and (2) volume errors extracted along the DVH curves were generated and summarized in tabular and graphical forms. Results: In Test 1, PINNACLE produced 52 deviations (15%) while PlanIQ produced 5 (1.5%). In Test 2, PINNACLE and PlanIQ differed from analytical by >3% in 93 (36%) and 18 (7%) times, respectively. Excluding D{sub min} and D{sub max} as least clinically relevant would result in 32 (15%) vs 5 (2%) scored deviations for PINNACLE vs PlanIQ in Test 1, while Test 2 would yield 53 (25%) vs 17 (8%). In Test 3, statistical analyses of volume errors extracted continuously along the curves show PINNACLE to have more errors and higher variability (relative to PlanIQ), primarily due to PINNACLE’s lack of sufficient 3D grid supersampling. Another major driver for PINNACLE errors is an inconsistency in implementation of the “end-capping”; the additional volume resulting from expanding superior and inferior contours halfway to the next slice is included in the total volume calculation, but dose voxels in this expanded volume are excluded from the DVH. PlanIQ had fewer deviations, and most were associated with a rotated cylinder modeled by rectangular axial contours; for coarser axial spacing, the limited number of cross-sectional rectangles hinders the ability to render the true structure volume. Conclusions: The method is applicable to any DVH-calculating software capable of importing DICOM RT structure set and dose objects (the authors’ examples are available for download). It includes a collection of tests that probe the design of the DVH algorithm, measure its accuracy, and identify failure modes. Merits and applicability of each test are discussed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-J-16: Automatic Image Contrast Enhancement Based On Automatic Parameter Optimization for Radiation Therapy Setup Verification

Purpose: In RT patient setup 2D images, tissues often cannot be seen well due to the lack of image contrast. Contrast enhancement features provided by image reviewing software, e.g. Mosaiq and ARIA, require manual selection of the image processing filters and parameters thus inefficient and cannot be automated. In this work, we developed a novel method to automatically enhance the 2D RT image contrast to allow automatic verification of patient daily setups as a prerequisite step of automatic patient safety assurance. Methods: The new method is based on contrast limited adaptive histogram equalization (CLAHE) and high-pass filtering algorithms. The most important innovation is to automatically select the optimal parameters by optimizing the image contrast. The image processing procedure includes the following steps: 1) background and noise removal, 2) hi-pass filtering by subtracting the Gaussian smoothed Result, and 3) histogram equalization using CLAHE algorithm. Three parameters were determined through an iterative optimization which was based on the interior-point constrained optimization algorithm: the Gaussian smoothing weighting factor, the CLAHE algorithm block size and clip limiting parameters. The goal of the optimization is to maximize the entropy of the processed Result. Results: A total 42 RT images were processed. The results were visually evaluated by RT physicians and physicists. About 48% of the images processed by the new method were ranked as excellent. In comparison, only 29% and 18% of the images processed by the basic CLAHE algorithm and by the basic window level adjustment process, were ranked as excellent. Conclusion: This new image contrast enhancement method is robust and automatic, and is able to significantly outperform the basic CLAHE algorithm and the manual window-level adjustment process that are currently used in clinical 2D image review software tools.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-J-71: Spatially Preserving Prior Knowledge-Based Treatment Planning

Purpose: Prior knowledge-based treatment planning is impeded by the use of a single dose volume histogram (DVH) curve. Critical spatial information is lost from collapsing the dose distribution into a histogram. Even similar patients possess geometric variations that becomes inaccessible in the form of a single DVH. We propose a simple prior knowledge-based planning scheme that extracts features from prior dose distribution while still preserving the spatial information. Methods: A prior patient plan is not used as a mere starting point for a new patient but rather stopping criteria are constructed. Each structure from the prior patient is partitioned into multiple shells. For instance, the PTV is partitioned into an inner, middle, and outer shell. Prior dose statistics are then extracted for each shell and translated into the appropriate Dmin and Dmax parameters for the new patient. Results: The partitioned dose information from a prior case has been applied onto 14 2-D prostate cases. Using prior case yielded final DVHs that was comparable to manual planning, even though the DVH for the prior case was different from the DVH for the 14 cases. Solely using a single DVH for the entire organ was also performed for comparison but showed a much poorer performance. Different ways of translating the prior dose statistics into parameters for the new patient was also tested. Conclusion: Prior knowledge-based treatment planning need to salvage the spatial information without transforming the patients on a voxel to voxel basis. An efficient balance between the anatomy and dose domain is gained through partitioning the organs into multiple shells. The use of prior knowledge not only serves as a starting point for a new case but the information extracted from the partitioned shells are also translated into stopping criteria for the optimization problem at hand.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-J-270: Repeated 18F-FDG PET/CTs Based Feature Analysis for the Predication of Anal Cancer Recurrence

Purpose: To identify PET/CT based imaging predictors of anal cancer recurrence and evaluate baseline vs. mid-treatment vs. post-treatment PET/CT scans in the tumor recurrence prediction. Methods: FDG-PET/CT scans were obtained at baseline, during chemoradiotherapy (CRT, midtreatment), and after CRT (post-treatment) in 17 patients of anal cancer. Four patients had tumor recurrence. For each patient, the mid-treatment and post-treatment scans were respectively aligned to the baseline scan by a rigid registration followed by a deformable registration. PET/CT image features were computed within the manually delineated tumor volume of each scan to characterize the intensity histogram, spatial patterns (texture), and shape of the tumors, as well as the changes of these features resulting from CRT. A total of 335 image features were extracted. An Exact Logistic Regression model was employed to analyze these PET/CT image features in order to identify potential predictors for tumor recurrence. Results: Eleven potential predictors of cancer recurrence were identified with p < 0.10, including five shape features, five statistical texture features, and one CT intensity histogram feature. Six features were indentified from posttreatment scans, 3 from mid-treatment scans, and 2 from baseline scans. These features indicated that there were differences in shape, intensity, and spatial pattern between tumors with and without recurrence. Recurrent tumors tended to have more compact shape (higher roundness and lower elongation) and larger intensity difference between baseline and follow-up scans, compared to non-recurrent tumors. Conclusion: PET/CT based anal cancer recurrence predictors were identified. The post-CRT PET/CT is the most important scan for the prediction of cancer recurrence. The baseline and mid-CRT PET/CT also showed value in the prediction and would be more useful for the predication of tumor recurrence in early stage of CRT. This work was supported in part by the National Cancer Institute Grant R01CA172638.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-618: Plan Robustness Study of Volumetric-Modulated Arc Therapy Vs. Intensity-Modulated Radiation Therapy for Head and Neck Cancer

Purpose: Lack of plan robustness may contribute to local failure in volumetric-modulated arc therapy (VMAT) to treat head and neck (H&N) cancer. Thus we compared plan robustness of VMAT with intensity-modulated radiation therapy (IMRT). Methods: VMAT and IMRT plans were created for 9 H&N cancer patients. For each plan, six new perturbed dose distributions were computed — one each for ± 3mm setup deviations along the S-I, A-P and L-R directions. We used three robustness quantification tools: (1) worst-case analysis (WCA); (2) dose-volume histograms (DVHs) band (DVHB); and (3) root-mean-square-dose deviation (RMSD) volume histogram (DDVH). DDVH represents the relative volume (y) on the vertical axis and the RMSD (x) on the horizontal axis. Similar to DVH, this means that y% of the volume of the indicated structure has the RMSD at least x Gy[RBE].The width from the first two methods at different target DVH indices (such as D95 and D5) and the area under the DDVH curves (AUC) for the target were used to indicate plan robustness. In these robustness quantification tools, the smaller the value, the more robust the plan is. Plan robustness evaluation metrics were compared using Wilcoxon test. Results: DVHB showed the width at D95 from IMRT to be larger than from VMAT (unit Gy) [1.59 vs 1.18 (p=0.49)], while the width at D5 from IMRT was found to be slightly larger than from VMAT [0.59 vs 0.54 (p=0.84)]. WCA showed similar results [D95: 3.28 vs 3.00 (p=0.56); D5: 1.68 vs 1.95 (p=0.23)]. DDVH showed the AUC from IMRT to be slightly smaller than from VMAT [1.13 vs 1.15 (p=0.43)]. Conclusion: VMAT plan robustness is comparable to IMRT plan robustness. The plan robustness conclusions from WCA and DVHB are DVH parameter dependent. On the other hand DDVH captures the overall effect of uncertainties on the dose to a volume of interest. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research Mayo ASU Seed Grant; The Kemper Marley Foundation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution. Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of tissues and similarity of electron density assignment. This method can allow MR-only treatment planning.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

MO-G-304-01: FEATURED PRESENTATION: Expanding the Knowledge Base for Data-Driven Treatment Planning: Incorporating Patient Outcome Models

Purpose: To extend the capabilities of knowledge-based treatment planning beyond simple dose queries by incorporating validated patient outcome models. Methods: From an analytic, relational database of 684 head and neck cancer patients, 372 patients were identified having dose data for both left and right parotid glands as well as baseline and follow-up xerostomia assessments. For each existing patient, knowledge-based treatment planning was simulated for by querying the dose-volume histograms and geometric shape relationships (overlap volume histograms) for all other patients. Dose predictions were captured at normalized volume thresholds (NVT) of 0%, 10%, 20, 30%, 40%, 50%, and 85% and were compared with the actual achieved doses using the Wilcoxon signed-rank test. Next, a logistic regression model was used to predict the maximum severity of xerostomia up to three months following radiotherapy. Baseline xerostomia scores were subtracted from follow-up assessments and were also included in the model. The relative risks from predicted doses and actual doses were computed and compared. Results: The predicted doses for both parotid glands were significantly less than the achieved doses (p < 0.0001), with differences ranging from 830 cGy ± 1270 cGy (0% NVT) to 1673 cGy ± 1197 cGy (30% NVT). The modelled risk of xerostomia ranged from 54% to 64% for achieved doses and from 33% to 51% for the dose predictions. Relative risks varied from 1.24 to 1.87, with maximum relative risk occurring at 85% NVT. Conclusions: Data-driven generation of treatment planning objectives without consideration of the underlying normal tissue complication probability may Result in inferior plans, even if quality metrics indicate otherwise. Inclusion of complication models in knowledge-based treatment planning is necessary in order to close the feedback loop between radiotherapy treatments and patient outcomes. Future work includes advancing and validating complication models in the context of knowledge-based treatment planning. This work is supported by Philips Radiation Oncology Systems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

TU-G-BRD-08: In-Vivo EPID Dosimetry: Quantifying the Detectability of Four Classes of Errors

Purpose: EPID dosimetry is an emerging method for treatment verification and QA. Given that the in-vivo EPID technique is in clinical use at some centers, we investigate the sensitivity and specificity for detecting different classes of errors. We assess the impact of these errors using dose volume histogram endpoints. Though data exist for EPID dosimetry performed pre-treatment, this is the first study quantifying its effectiveness when used during patient treatment (in-vivo). Methods: We analyzed 17 patients; EPID images of the exit dose were acquired and used to reconstruct the planar dose at isocenter. This dose was compared to the TPS dose using a 3%/3mm gamma criteria. To simulate errors, modifications were made to treatment plans using four possible classes of error: 1) patient misalignment, 2) changes in patient body habitus, 3) machine output changes and 4) MLC misalignments. Each error was applied with varying magnitudes. To assess the detectability of the error, the area under a ROC curve (AUC) was analyzed. The AUC was compared to changes in D99 of the PTV introduced by the simulated error. Results: For systematic changes in the MLC leaves, changes in the machine output and patient habitus, the AUC varied from 0.78–0.97 scaling with the magnitude of the error. The optimal gamma threshold as determined by the ROC curve varied between 84–92%. There was little diagnostic power in detecting random MLC leaf errors and patient shifts (AUC 0.52–0.74). Some errors with weak detectability had large changes in D99. Conclusion: These data demonstrate the ability of EPID-based in-vivo dosimetry in detecting variations in patient habitus and errors related to machine parameters such as systematic MLC misalignments and machine output changes. There was no correlation found between the detectability of the error using the gamma pass rate, ROC analysis and the impact on the dose volume histogram. Funded by grant R18HS022244 from AHRQ.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

WE-G-BRD-01: A Data-Driven 4D-MRI Motion Model to Estimate Full Field-Of-View Abdominal Motion From 2D Image Navigators During MR-Linac Treatment

Purpose: To estimate full field-of-view abdominal respiratory motion from fast 2D image navigators using a 4D-MRI based motion model. This will allow for radiation dose accumulation mapping during MR-Linac treatment. Methods: Experiments were conducted on a Philips Ingenia 1.5T MRI. First, a retrospectively ordered 4D-MRI was constructed using 3D transient-bSSFP with radial in-plane sampling. Motion fields were calculated through 3D non-rigid registration. From these motion fields a PCA-based abdominal motion model was constructed and used to warp a 3D reference volume to fast 2D cine-MR image navigators that can be used for real-time tracking. To test this procedure, a time-series consisting of two interleaved orthogonal slices (sagittal and coronal), positioned on the pancreas or kidneys, were acquired for 1m38s (dynamic scan-time=0.196ms), during normal, shallow, or deep breathing. The coronal slices were used to update the optimal weights for the first two PCA components, in order to warp the 3D reference image and construct a dynamic 4D-MRI time-series. The interleaved sagittal slices served as an independent measure to test the model’s accuracy and fit. Spatial maps of the root-mean-squared error (RMSE) and histograms of the motion differences within the pancreas and kidneys were used to evaluate the method. Results: Cranio-caudal motion was accurately calculated within the pancreas using the model for normal and shallow breathing with an RMSE of 1.6mm and 1.5mm and a histogram median and standard deviation below 0.2 and 1.7mm, respectively. For deep-breathing an underestimation of the inhale amplitude was observed (RMSE=4.1mm). Respiratory-induced antero-posterior and lateral motion were correctly mapped (RMSE=0.6/0.5mm). Kidney motion demonstrated good motion estimation with RMSE-values of 0.95 and 2.4mm for the right and left kidney, respectively. Conclusion: We have demonstrated a method that can calculate dynamic 3D abdominal motion in a large volume, while acquiring real-time cine-MR images for MR-guided radiotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Projections onto the Pareto surface in multicriteria radiation therapy optimization

Purpose: To eliminate or reduce the error to Pareto optimality that arises in Pareto surface navigation when the Pareto surface is approximated by a small number of plans. Methods: The authors propose to project the navigated plan onto the Pareto surface as a postprocessing step to the navigation. The projection attempts to find a Pareto optimal plan that is at least as good as or better than the initial navigated plan with respect to all objective functions. An augmented form of projection is also suggested where dose–volume histogram constraints are used to prevent that the projection causes a violation of some clinical goal. The projections were evaluated with respect to planning for intensity modulated radiation therapy delivered by step-and-shoot and sliding window and spot-scanned intensity modulated proton therapy. Retrospective plans were generated for a prostate and a head and neck case. Results: The projections led to improved dose conformity and better sparing of organs at risk (OARs) for all three delivery techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on average for the unconstrained form of the projection and by 2.0 Gy on average when dose–volume histogram constraints were used. No consistent improvements in target homogeneity were observed. Conclusions: There are situations when Pareto navigation leaves room for improvement in OAR sparing and dose conformity, for example, if the approximation of the Pareto surface is coarse or the problem formulation has too permissive constraints. A projection onto the Pareto surface can identify an inaccurate Pareto surface representation and, if necessary, improve the quality of the navigated plan.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies

Purpose: To develop and evaluate a fast and simple tool called dPETSTEP (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images. Methods: The tool was developed in MATLAB using both new and previously reported modules of PETSTEP (PET Simulator of Tracers via Emission Projection). Time activity curves are generated for each voxel of the input parametric image, whereby effects of imaging system blurring, counting noise, scatters, randoms, and attenuation are simulated for each frame. Each frame is then reconstructed into images according to the user specified method, settings, and corrections. Reconstructed images were compared to MC data, and simple Gaussian noised time activity curves (GAUSS). Results: dPETSTEP was 8000 times faster than MC. Dynamic images from dPETSTEP had a root mean square error that was within 4% on average of that of MC images, whereas the GAUSS images were within 11%. The average bias in dPETSTEP and MC images was the same, while GAUSS differed by 3% points. Noise profiles in dPETSTEP images conformed well to MC images, confirmed visually by scatter plot histograms, and statistically by tumor region of interest histogram comparisons that showed no significant differences (p < 0.01). Compared to GAUSS, dPETSTEP images and noise properties agreed better with MC. Conclusions: The authors have developed a fast and easy one-stop solution for simulations of dynamic PET and parametric images, and demonstrated that it generates both images and subsequent parametric images with very similar noise properties to those of MC images, in a fraction of the time. They believe dPETSTEP to be very useful for generating fast, simple, and realistic results, however since it uses simple scatter and random models it may not be suitable for studies investigating these phenomena. dPETSTEP can be downloaded free of cost from https://github.com/CRossSchmidtlein/dPETSTEP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-C-BRA-06: Automatic Brain Tumor Segmentation for Stereotactic Radiosurgery Applications

Purpose: Stereotactic radiosurgery (SRS), which delivers a potent dose of highly conformal radiation to the target in a single fraction, requires accurate tumor delineation for treatment planning. We present an automatic segmentation strategy, that synergizes intensity histogram thresholding, super-voxel clustering, and level-set based contour evolving methods to efficiently and accurately delineate SRS brain tumors on contrast-enhance T1-weighted (T1c) Magnetic Resonance Images (MRI). Methods: The developed auto-segmentation strategy consists of three major steps. Firstly, tumor sites are localized through 2D slice intensity histogram scanning. Then, super voxels are obtained through clustering the corresponding voxels in 3D with reference to the similarity metrics composited from spatial distance and intensity difference. The combination of the above two could generate the initial contour surface. Finally, a localized region active contour model is utilized to evolve the surface to achieve the accurate delineation of the tumors. The developed method was evaluated on numerical phantom data, synthetic BRATS (Multimodal Brain Tumor Image Segmentation challenge) data, and clinical patients’ data. The auto-segmentation results were quantitatively evaluated by comparing to ground truths with both volume and surface similarity metrics. Results: DICE coefficient (DC) was performed as a quantitative metric to evaluate the auto-segmentation in the numerical phantom with 8 tumors. DCs are 0.999±0.001 without noise, 0.969±0.065 with Rician noise and 0.976±0.038 with Gaussian noise. DC, NMI (Normalized Mutual Information), SSIM (Structural Similarity) and Hausdorff distance (HD) were calculated as the metrics for the BRATS and patients’ data. Assessment of BRATS data across 25 tumor segmentation yield DC 0.886±0.078, NMI 0.817±0.108, SSIM 0.997±0.002, and HD 6.483±4.079mm. Evaluation on 8 patients with total 14 tumor sites yield DC 0.872±0.070, NMI 0.824±0.078, SSIM 0.999±0.001, and HD 5.926±6.141mm. Conclusion: The developed automatic segmentation strategy, which yields accurate brain tumor delineation in evaluation cases, is promising for its application in SRS treatment planning.

60 APPLIED LIFE SCIENCES↗