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Assessment and management of interfractional variations in daily diagnostic-quality-CT guided prostate-bed irradiation after prostatectomy

Purpose: To quantify interfractional anatomic variations and limitations of the current practice of image-guided radiation therapy (IGRT) for prostate-bed patients and to study dosimetric benefits of an online adaptive replanning scheme that addresses the interfractional variations. Methods: Contours for the targets and organs at risk (OARs) from daily diagnostic-quality CTs acquired with in-room CT (CTVision, Siemens) were generated by populating the planning contours using an autosegmentation tool based on deformable registration (ABAS, Elekta) with manual editing for ten prostate-bed patients treated with postoperative daily CT-guided IMRT. Dice similarity coefficient (DSC) obtained by maximizing the overlap of contours for a structure between the daily and plan contours was used to quantify the organ deformation between the plan and daily CTs. Three interfractional-variation-correction schemes, the current standard practice of IGRT repositioning, a previously developed online adaptive RT (ART), and the full reoptimization, were applied to these daily CTs and a number of dose-volume quantities for the targets and organs at risk were compared for their effectiveness to account for the interfractional variations. Results: Large interfractional organ deformations in prostate-bed irradiation were seen. The mean DSCs for CTV, rectum, and bladder were 86.6 ± 5.1% (range from 61% to 97%), 77.3% ± 7.4% (range from 55% to 90%), and 75.4% ± 11.2% (range from 46% to 96%), respectively. The fractional and cumulative dose-volume quantities for CTV and PTV: V100 (volume received at least 100% prescription dose), and rectum and bladder: V{sub 45Gy} and V{sub 60Gy} (volume received at least 45 or 60 Gy), were compared for the repositioning, adaptive, reoptimization, and original plans. The fractional and cumulative dosimetric results were nearly the same. The average cumulative CTV V100 were 88.0%, 98.4%, 99.2%, and 99.3% for the IGRT, ART, reoptimization, and original plans, respectively. The corresponding rectal V{sub 45Gy} (V{sub 60Gy}) were 58.7% (27.3%), 48.1% (20.7%), 43.8% (16.1%), and 44.9% (16.8%). The results for bladder were comparable among three schemes. Paired two-tailed Wilcoxon signed-rank tests were performed and it was found that ART and reoptimization provide better target coverage and better OAR sparing, especially rectum sparing. Conclusions: The interfractional organ motions and deformations during prostate-bed irradiation are significant. The online adaptive replanning scheme is capable of effectively addressing the large organ deformation, resulting in cumulative doses equivalent to those originally planned.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-J-27: Appropriateness Criteria for Deformable Image Registration and Dose Propagation

Purpose: Several commercial software packages have been recently released that allow the user to apply deformable registration algorithms (DRA) for image fusion and dose propagation. Although the idea of anatomically tracking the daily patient dose in the context of adaptive radiotherapy or merely adding the dose from prior treatment to the current one is very intuitive, the accuracy and applicability of such algorithms needs to be investigated as it remains somewhat subjective. In our study, we used true anatomical data where we introduced changes in the density, volume and location of segmented structures to test the DRA for its sensitivity and accuracy. Methods: The CT scan of a prostate patient was selected for this study. The CT images were first segmented to define structure such as the PTV, bladder, rectum, intestines and pelvic bone anatomy. To perform our study, we introduced anatomical changes in the reference patient image set in three different ways: (i) we kept the segmented volumes constant and changed the density of rectum and bladder in increments of 5% (ii) we changed the volume of rectum and bladder in increments of 5% and (iii) we kept the segmented volumes constant but changed their location by moving their COM in increments of 3mm. Using the Velocity software, we evaluated the accuracy of the DRA for each incremental change in all three scenarios. Results: The DRA performs reasonably well when the differential density difference against the background is more than 5%. For the volume change study, the DRA results became unreliable for relative volume changes greater than 10%. Finally for the location study, the DRA performance was acceptable for shifts below 9mm. Conclusion: Site specific and patient specific QA for DRA is an important step to evaluate such algorithms prior to their use for dose propagation.

60 APPLIED LIFE SCIENCES↗

SU-E-J-62: Estimating Plausible Treatment Course Dose Distributions by Accounting for Registration Uncertainty and Organ Motion

Purpose: Dose accumulation following deformable image registration (DIR) is challenging. In this study, we used a statistical sampling approach, which takes into account both DIR uncertainties and patient-specific organ motion, to study the distribution of possible true dose distributions. Methods: The study included ten patients (six CT scans/patient) treated with radiotherapy for prostate cancer. For each patient, the planned dose was re-calculated on the repeated geometries, following rigid registration based on fiducial markers. The dose re-calculated on the first CT served as our snapshot dose distribution (D1) and the average of the first five repeat scans as our treatment course reference dose distribution (Dref). Patient-specific motion and DIR-uncertainties, at each voxel in CT1, were assessed using a previously developed DIR performance measure, the distance discordance metric (DDM). To sample the distribution of possible true, predicted dose distributions (Dpred), we resampled D1 by perturbing the location of each voxel with the corresponding DDM. The three dose distribution approaches are compared for the rectum and the bladder. Results: The bladder generalized equivalent uniform dose (gEUD) from the averaged Dpred was closer to the gEUDref than to the gEUD1 (difference: 0.6 vs. 1.0 Gy). For both structures, the gEUDpred was higher than the gEUDref, and significantly higher (p≤0.05) for the rectum (average: 50.8 Gy vs. 48.0 Gy). Conclusion: We have shown that the bladder gEUD values resulting from our DIR-uncertainty inclusive dose sampling approach, Dpred, were closer to the gEUD from Dref than the gEUD values from D1. For the rectum, gEUDpred overestimated gEUDref. Theoretically however, gEUDpred values, sampled from DDM uncertainties are more representative of dose uncertainties.

60 APPLIED LIFE SCIENCES↗

SU-E-T-125: Dosimetric Comparison of Intensity Modulated Radiation Therapy Using Robotic Versus Traditional Linac Platform in Prostate Cancer

Purpose: Recent development of an MLC for robotic external beam radiotherapy has the potential of new clinical application in conventionally fractionated radiation therapy. This study offers a dosimetric comparison of IMRT plans using Cyberknife with MLC versus conventional linac plans. Methods: Ten prostate cancer patients treated on a traditional linac with IMRT to 7920cGy at 180cGy/fraction were randomly selected. GTVs were defined as prostate plus proximal seminal vesicles. PTVs were defined as GTV+8mm in all directions except 5mm posteriorly. Conventional IMRT planning was performed on Philips Pinnacle and delivered on a standard linac with CBCT and 10mm collimator leaf width. For each case a Cyberknife plan was created using Accuray Multiplan with same CT data set, contours, and dose constraints. All dosimetric data was transferred to third party software for independent computation of contour volumes and DVH. Delivery efficiency was evaluated using total MU, treatment time, number of beams, and number of segments. Results: Evaluation criteria including percent target coverage, homogeneity index, and conformity index were found to be comparable. All dose constraints from QUANTEC were found to be statistically similar except rectum V50Gy and bladder V65Gy. Average rectum V50Gy was lower for robotic IMRT (30.07%±6.57) versus traditional (34.73%±3.62, p=0.0130). Average bladder V65Gy was lower for robotic (17.87%±12.74) versus traditional (21.03%±11.93, p=0.0405). Linac plans utilized 9 coplanar beams, 48.9±3.8 segments, and 19381±2399MU. Robotic plans utilized 38.4±9.0 non-coplanar beams, 85.5±21.0 segments and 42554.71±16381.54 MU. The average treatment was 15.02±0.60 minutes for traditional versus 20.90±2.51 for robotic. Conclusion: The robotic IMRT plans were comparable to the traditional IMRT plans in meeting the target volume dose objectives. Critical structure dose constraints were largely comparable although statistically significant differences were found in favor of the robotic platform in terms of rectum V50Gy and bladder V65Gy at a cost of 25% longer treatment time.

60 APPLIED LIFE SCIENCES↗

SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRT or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.

60 APPLIED LIFE SCIENCES↗

SU-F-BRD-11: Prediction of Dosimetric Endpoints From Patient Geometry Using Neural Nets

Purpose: The previously-published overlap volume histogram (OVH) technique lends itself naturally to prediction of the dose received by a given volume of tissue (e.g. D90) in intensity-modulated radiotherapy (IMRT) treatment plans. Here we extend the OVH technique using artificial neural networks in order to predict the volume of tissue receiving a given dose (e.g. V90) in both prostate IMRT and conventional breast radiotherapy. Methods: Twenty-nine prostate treatment plans and forty-three breast treatment plans were analyzed. The spatial relationships between the prostate and rectum and between the breast and ipsilateral lung were characterized using OVHs. The OVH is a cumulative histogram representing the fractional volume of the risk organ overlapped by a series of isotropic expansions of the planning target volume (PTV). Seven cases were identified as outliers and replanned. OVH points were used as inputs to a one hidden layer feed forward artificial neural network with quality parameters of the corresponding plan, such as the rectum V50, as targets. A 3-fold cross-validation was used to estimate the prediction error. Results: The root mean square (RMS) error between the predicted rectum V50s and the planned values was 2.3, which was 35% of the standard deviation of V50 for the twenty-nine plans. The RMS error of prediction of V20 of the ipsilateral lung in breast cases was 3.9, which was 90% of the standard deviation of the V20 values in the breast plan database. Conclusion: This study demonstrates that artificial neural nets can be used to extend the OVH technique to predict dosimetric endpoints taking the form of a volume receiving a given dose, rather than the minimum dose received by a given volume. Prediction of ipsilateral lung dose in breast radiotherapy using the OVH technique remains a work in progress.

60 APPLIED LIFE SCIENCES↗

Poster — Thur Eve — 13: Inter-Fraction Target Movement in Image-Guided Radiation Therapy of Prostate Cancer

We investigated the setup variations over the treatment courses of 113 patients with intact prostate treated with 78Gy/39fx. Institutional standard bladder and bowel preparation and image guidance protocols were used in CT simulation and treatment. The RapidArc treatment plans were optimized in Varian Eclipse treatment planning system and delivered on Varian 2100X Clinacs equipped with On-Board Imager to localize the target before beam-on. The setup variations were calculated in terms of mean and standard deviation of couch shifts. No correlation was observed between the mean shift and standard deviation over the treatment course and patient age, initial prostate volume and rectum size. The mean shifts in the first and last 5 fractions are highly correlated (P < 10{sup −10}) while the correlation of the standard deviations cannot be determined. The Mann-Kendall tests indicate trends of the mean daily Ant-Post and Sup-Inf shifts of the group. The target is inferior by ∼1mm to the planned position when the treatment starts and moves superiorly, approaching the planned position at 10th fraction, and then gradually moves back inferiorly by ∼1mm in the remain fractions. In the Ant-Post direction, the prostate gradually moves posteriorly during the treatment course from a mean shift of ∼2.5mm in the first fraction to ∼1mm in the last fraction. It may be related to a systematic rectum size change in the progress of treatment. The biased mean shifts in Ant-Post and Sup-Inf direction of most patients suggest systematically larger rectum and smaller bladder during the treatment than at CT simulation.

60 APPLIED LIFE SCIENCES↗

SU-C-213-07: Fabrication and Testing of a 3D-Printed Small Animal Rectal Cooling Device to Evaluate Local Hypothermia as a Radioprotector During Prostate SBRT

Purpose: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to SBRT treatments. Relevant to prostate SBRT, this work details the fabrication and testing of a 3D-printed cooling device to facilitate the investigation of the radioprotective effect of local hypothermia on the rat rectum. Methods: A 3cm long, two-channel rectal cooling device was designed in SOLIDWORKS CAD for 3D printing. The water intake nozzle is connected to a 1mm diameter brass pipe from which water flows and circulates back around to the exit nozzle. Both nozzles are connected by plastic tubing to a water chiller pump. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within a rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. CBCT images from a small-animal irradiator were evaluated for imaging artifacts which could affect Monte Carlo dose calculations during treatment planning. Results: The rectal temperature adjacent to the cooling device decreased from body temperature (37°C) to 15°C in 10–20 minutes from device insertion. Rectal temperature was maintained at 15±3°C during active cooling. MRI thermometry tests revealed a steep temperature gradient with increasing distance from the cooling device, with the desired temperature range maintained within the surrounding few millimeters. Conclusion: A 3D printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in rat rectums. Rectal cooling capabilities were characterized in-vivo to facilitate an investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation. Funding support provided by RSNA research seed grant.

60 APPLIED LIFE SCIENCES↗

SU-E-T-310: Dosimetric Comparison of Tandem and Ovoid (TO) Vs. Tandem and Ring (TR) Applicators in High-Dose Rate (HDR) Brachytherapy (BT) for the Treatment of Locally-Advanced Cervical-Cancer

Purpose: To investigate the dosimetric differences associated with the use of TO or TR applicators for cervical-cancer HDR BT. Methods: The records of all cervical-cancer patients treated with image-guided HDR BT in 2013 were reviewed. Image-based planning based on isodose line and DVH metrics inspections was performed following the GEC-ESTRO recommendations. CTV volume, CTV D90, and rectum, bladder and sigmoid D2cc were collected as % of the prescription dose (80Gy EQD2). Patients receiving both TO and TR were identified and plans were compared (paired analysis). A Student T-test was used to evaluate statistical significance (p ≤ 0.05). Results: Twenty-eight patients were identified (20 TR only, 4 TO only, 4 TO and TR), associated with 116 plans (109 TR, 7 TO). Overall metrics: CTV volume, 26.5±10.4 cm3 (TR) and 39.1±14.0 cm3 (TO, p < 0.01); CTV D90, 126±28% (TR) and 110±15% (TO, p = 0.15); rectum D2cc, 56±11% (TR) and 58±19% (TO, p = 0.91); bladder D2cc, 74±20% (TR) and 88±19% (TO, p = 0.09); sigmoid D2cc, 52±17% (TR) and 49±20% (TO, p = 0.63). The paired analysis results were: CTV volume, 37.3±11.9 cm3 (TR) and 51.0±23.1 cm3 (TO, p = 0.23); CTV D90, 111±12% (TR) and 101±17% (TO, p = 0.50); rectum D2cc, 56±12% (TR) and 53±16% (TO, p = 0.71); bladder D2cc, 73±14% (TR) and 90±20% (TO, p = 0.22); sigmoid D2cc, 59±10% (TR) and 59±22% (TO, p = 0.98). Conclusion: TR and TO were both used with good dosimetric results. TO were used for patients with larger CTV volumes than TR, although paired analysis suggest that tissue distortion and contouring bias may partially explain this Result. CTV D90 on average > 80 Gy EQD2 were achieved in both groups despite the different CTV volume. Higher bladder D2cc for TO than TR was observed.

60 APPLIED LIFE SCIENCES↗

SU-E-T-332: Dosimetric Impact of Photon Energy and Treatment Technique When Knowledge Based Auto-Planning Is Implemented in Radiotherapy of Localized Prostate Cancer

Purpose: The aim of this study was to investigate the dosimetric impact of the combination of photon energy and treatment technique on radiotherapy of localized prostate cancer when knowledge based planning was used. Methods: A total of 16 patients with localized prostate cancer were retrospectively retrieved from database and used for this study. For each patient, four types of treatment plans with different combinations of photon energy (6X and 10X) and treatment techniques (7-field IMRT and 2-arc VMAT) were created using a prostate DVH estimation model in RapidPlan™ and Eclipse treatment planning system (Varian Medical System). For any beam arrangement, DVH objectives and weighting priorities were generated based on the geometric relationship between the OAR and PTV. Photon optimization algorithm was used for plan optimization and AAA algorithm was used for final dose calculation. Plans were evaluated in terms of the pre-defined dosimetric endpoints for PTV, rectum, bladder, penile bulb, and femur heads. A Student’s paired t-test was used for statistical analysis and p > 0.05 was considered statistically significant. Results: For PTV, V95 was statistically similar among all four types of plans, though the mean dose of 10X plans was higher than that of 6X plans. VMAT plans showed higher heterogeneity index than IMRT plans. No statistically significant difference in dosimetry metrics was observed for rectum, bladder, and penile bulb among plan types. For left and right femur, VMAT plans had a higher mean dose than IMRT plans regardless of photon energy, whereas the maximum dose was similar. Conclusion: Overall, the dosimetric endpoints were similar regardless of photon energy and treatment techniques when knowledge based auto planning was used. Given the similarity in dosimetry metrics of rectum, bladder, and penile bulb, the genitourinary and gastrointestinal toxicities should be comparable among the selections of photon energy and treatment techniques.

60 APPLIED LIFE SCIENCES↗

SU-E-T-334: Dosimetric Impacts of Organ at Risk (OAR) Contour Errors in Prostate Volumetric Modulated Arc Therapy (VMAT) Planning: A Sensitivity Study

Purpose: To investigate the dosimetric impacts of OAR contour errors in prostate VMAT planning with a sensitivity analysis method. Methods: Ten randomly selected prostate VMAT patients were used to simulate OAR contour error in rectum and bladder. For each OAR 12 even spaced contour control points were selected in every three slices. For each simulation, only one of the control points was simulated to move inwards or outwards by up to 6 voxels and coordinates of adjacent voxels to that moving control point were moved accordingly with a 3D-spline smooth function. An in-house software was used to predict OARs dosimetric endpoints based on geometric relationship between PTV and OAR. In this study, the V75, V70, V65, V60 of rectum and V80, V75, V70, V65 of bladder with and without perturbed contours were calculated and compared. Results: The percentage of OAR dose volume difference around the reference OAR contours were plotted as iso-error lines overlaid on CT images. The significant difference was shown in OAR contours adjacent to the PTV where high dose gradient exists. When one of the 12 points adjacent to the PTV moved up to 6 voxels, maximum errors of 1.99%, 2.46%, 2.89%, and 3.19% were found in V75, V70, V65, and V60 of the rectum, and 1.59%, 1.67%, 1.87%, and 1.90% were found in V80, V75, V70, and V65 of the bladder, respectively. Conclusion: We can quantify the dosimetric impact of OAR contouring error by evaluating the percentage of OAR dose volume changes in prostate VMAT planning. For the adaptive radiation therapy, the iso-error lines can provide the planner a guideline that which portion of contour needed to be checked carefully because dosimetric sensitivity of contour errors are different for different part of contours.

60 APPLIED LIFE SCIENCES↗

Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy

Purpose: Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. Methods: The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. Results: Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. Conclusions: The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.

60 APPLIED LIFE SCIENCES↗

SU-F-J-81: Evaluation of Automated Deformable Registration Between Planning Computed Tomography (CT) and Daily Cone Beam CT Images Over the Course of Prostate Cancer Radiotherapy

Purpose: To compute daily dose delivered during radiotherapy, deformable registration needs to be relatively fast, automated, and accurate. The aim of this study was to evaluate the performance of commercial deformable registration software for deforming between two modalities: planning computed tomography (pCT) images acquired for treatment planning and cone beam (CB) CT images acquired prior to each fraction of prostate cancer radiotherapy. Methods: A workflow was designed using MIM Software™ that aligned and deformed pCT into daily CBCT images in two steps: (1) rigid shifts applied after daily CBCT imaging to align patient anatomy to the pCT and (2) normalized intensity-based deformable registration to account for interfractional anatomical variations. The physician-approved CTV and organ and risk (OAR) contours were deformed from the pCT to daily CBCT over the course of treatment. The same structures were delineated on each daily CBCT by a radiation oncologist. Dice similarity coefficient (DSC) mean and standard deviations were calculated to quantify the deformable registration quality for prostate, bladder, rectum and femoral heads. Results: To date, contour comparisons have been analyzed for 31 daily fractions of 2 of 10 of the cohort. Interim analysis shows that right and left femoral head contours demonstrate the highest agreement (DSC: 0.96±0.02) with physician contours. Additionally, deformed bladder (DSC: 0.81±0.09) and prostate (DSC: 0.80±0.07) have good agreement with physician-defined daily contours. Rectum contours have the highest variations (DSC: 0.66±0.10) between the deformed and physician-defined contours on daily CBCT imaging. Conclusion: For structures with relatively high contrast boundaries on CBCT, the MIM automated deformable registration provided accurate representations of the daily contours during treatment delivery. These findings will permit subsequent investigations to automate daily dose computation from CBCT. However, improved methods need to be investigated to improve deformable results for rectum contours.

60 APPLIED LIFE SCIENCES↗

SU-F-J-84: Comparison of Quantitative Deformable Image Registration Evaluation Tools: Application to Prostate IGART

Purpose: Errors in displacement vector fields (DVFs) generated by Deformable Image Registration (DIR) algorithms can give rise to significant uncertainties in contour propagation and dose accumulation in Image-Guided Adaptive Radiotherapy (IGART). The purpose of this work is to assess the accuracy of two DIR algorithms using a variety of quality metrics for prostate IGART. Methods: Pelvic CT images were selected from an anonymized database of nineteen prostate patients who underwent 8–12 serial scans during radiotherapy. Prostate, bladder, and rectum were contoured on 34 image-sets for three patients by the same physician. The planning CT was deformably-registered to daily CT using three variants of the Small deformation Inverse Consistent Linear Elastic (SICLE) algorithm: Grayscale-driven (G), Contour-driven (C, which utilizes segmented structures to drive DIR), combined (G+C); and also grayscale ITK demons (Gd). The accuracy of G, C, G+C SICLE and Gd registrations were evaluated using a new metric Edge Gradient Distance to Agreement (EGDTA) and other commonly-used metrics such as Pearson Correlation Coefficient (PCC), Dice Similarity Index (DSI) and Hausdorff Distance (HD). Results: C and G+C demonstrated much better performance at organ boundaries, revealing the lowest HD and highest DSI, in prostate, bladder and rectum. G+C demonstrated the lowest mean EGDTA (1.14 mm), which corresponds to highest registration quality, compared to G and C DVFs (1.16 and 2.34 mm). However, demons DIR showed the best overall performance, revealing lowest EGDTA (0.73 mm) and highest PCC (0.85). Conclusion: As expected, both C- and C+G SICLE more accurately reproduce manually-contoured target datasets than G-SICLE or Gd using HD and DSI metrics. In general, the Gd appears to have difficulty reproducing large daily position and shape changes in the rectum and bladder. However, Gd outperforms SICLE in terms of EGDTA and PCC metrics, possibly at the expense of topological quality of the estimated DVFs.

60 APPLIED LIFE SCIENCES↗

SU-F-J-203: Retrospective Assessment of Delivered Proton Dose in Prostate Cancer Patients Based On Daily In-Room CT Imaging

Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonal X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%<107%), bladder (V75Gy<15%, V70Gy<25%, V65Gy<30%), rectum (V70Gy<10%, V50Gy<40%) and femoral heads (V50Gy<5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Results: No alarming differences were observed between planned and retrospectively accumulated dose: iCTV constraints were met, except for one patient (D98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (<11.3%) in two patients. First intra-therapy variability analysis in 4 patients showed no timedependent parameter drift, revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare interventions after daily 3D imaging of the first 12 patients, in-room CT frequency for prostate cancer patients was reduced. The presented study supports this decision. The authors acknowledge the German Federal Ministry for Education and Research for funding the High Precision Radiotherapy Group at the OncoRay - National Center for Radiation Research in Oncology (BMBF- 03Z1N51).

60 APPLIED LIFE SCIENCES↗

SU-F-T-15: Evaluation of 192Ir, 60Co and 169Yb Sources for High Dose Rate Prostate Brachytherapy Inverse Planning Using An Interior Point Constraint Generation Algorithm

Purpose: The effectiveness of using a combination of three sources, {sup 60}Co, {sup 192}Ir and {sup 169}Yb, is analyzed. Different combinations are compared against a single {sup 192}Ir source on prostate cancer cases. A novel inverse planning interior point algorithm is developed in-house to generate the treatment plans. Methods: Thirteen prostate cancer patients are separated into two groups: Group A includes eight patients with the prostate as target volume, while group B consists of four patients with a boost nodule inside the prostate that is assigned 150% of the prescription dose. The mean target volume is 35.7±9.3cc and 30.6±8.5cc for groups A and B, respectively. All patients are treated with each source individually, then with paired sources, and finally with all three sources. To compare the results, boost volume V150 and D90, urethra Dmax and D10, and rectum Dmax and V80 are evaluated. For fair comparison, all plans are normalized to a uniform V100=100. Results: Overall, double- and triple-source plans were better than single-source plans. The triple-source plans resulted in an average decrease of 21.7% and 1.5% in urethra Dmax and D10, respectively, and 8.0% and 0.8% in rectum Dmax and V80, respectively, for group A. For group B, boost volume V150 and D90 increased by 4.7% and 3.0%, respectively, while keeping similar dose delivered to the urethra and rectum. {sup 60}Co and {sup 192}Ir produced better plans than their counterparts in the double-source category, whereas {sup 60}Co produced more favorable results than the remaining individual sources. Conclusion: This study demonstrates the potential advantage of using a combination of two or three sources, reflected in dose reduction to organs-at-risk and more conformal dose to the target. three sources, reflected in dose reduction to organs-at-risk and more conformal dose to the target. Our results show that {sup 60}Co, {sup 192}Ir and {sup 169}Yb produce the best plans when used simultaneously and can thus be an alternative to {sup 192}Ir-only in high-dose-rate prostate brachytherapy.

60 APPLIED LIFE SCIENCES↗

SU-F-T-18: The Importance of Immobilization Devices in Brachytherapy Treatments of Vaginal Cuff

Purpose: High dose rate brachytherapy is a highly localized radiation therapy that has a very high dose gradient. Thus one of the most important parts of the treatment is the immobilization. The smallest movement of the patient or applicator can result in dose variation to the surrounding tissues as well as to the tumor to be treated. We will revise the ML Cylinder treatments and their localization challenges. Methods: A retrospective study of 25 patients with 5 treatments each looking into the applicator’s placement in regard to the organs at risk. Motion possibilities for each applicator intra and inter fractionation with their dosimetric implications were covered and measured in regard with their dose variance. The localization immobilization devices used were assessed for the capability to prevent motion before and during the treatment delivery. Results: We focused on the 100% isodose on central axis and a 15 degree displacement due to possible rotation analyzing the dose variations to the bladder and rectum walls. The average dose variation for bladder was 15% of the accepted tolerance, with a minimum variance of 11.1% and a maximum one of 23.14% on the central axis. For the off axis measurements we found an average variation of 16.84% of the accepted tolerance, with a minimum variance of 11.47% and a maximum one of 27.69%. For the rectum we focused on the rectum wall closest to the 120% isodose line. The average dose variation was 19.4%, minimum 11.3% and a maximum of 34.02% from the accepted tolerance values Conclusion: Improved immobilization devices are recommended. For inter-fractionation, localization devices are recommended in place with consistent planning in regards with the initial fraction. Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment.

60 APPLIED LIFE SCIENCES↗

SU-F-T-97: Outlier Identification in Radiation Therapy Knowledge Modeling

Purpose: To investigate the impact of outliers on knowledge modeling in radiation therapy, and develop a systematic workflow for identifying and analyzing geometric and dosimetric outliers using pelvic cases. Methods: Four groups (G1-G4) of pelvic plans were included: G1 (37 prostate cases), G2 (37 prostate plus lymph node cases), and G3 (37 prostate bed cases) are all clinical IMRT cases. G4 are 10 plans outside G1 re-planned with dynamic-arc to simulate dosimetric outliers. The workflow involves 2 steps: 1. identify geometric outliers, assess impact and clean up; 2. identify dosimetric outliers, assess impact and clean up.1. A baseline model was trained with all G1 cases. G2/G3 cases were then individually added to the baseline model as geometric outliers. The impact on the model was assessed by comparing leverage statistic of inliers (G1) and outliers (G2/G3). Receiver-operating-characteristics (ROC) analysis was performed to determine optimal threshold. 2. A separate baseline model was trained with 32 G1 cases. Each G4 case (dosimetric outliers) was then progressively added to perturb this model. DVH predictions were performed using these perturbed models for remaining 5 G1 cases. Normal tissue complication probability (NTCP) calculated from predicted DVH were used to evaluate dosimetric outliers’ impact. Results: The leverage of inliers and outliers was significantly different. The Area-Under-Curve (AUC) for differentiating G2 from G1 was 0.94 (threshold: 0.22) for bladder; and 0.80 (threshold: 0.10) for rectum. For differentiating G3 from G1, the AUC (threshold) was 0.68 (0.09) for bladder, 0.76 (0.08) for rectum. Significant increase in NTCP started from models with 4 dosimetric outliers for bladder (p<0.05), and with only 1 dosimetric outlier for rectum (p<0.05). Conclusion: We established a systematic workflow for identifying and analyzing geometric and dosimetric outliers, and investigated statistical metrics for detecting. Results validated the necessity for outlier detection and clean-up to enhance model quality in clinical practice. Research Grant: Varian master research grant.

60 APPLIED LIFE SCIENCES↗