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At least 703 records · Page 39

SU-E-T-811: Volumetric Modulated Arc Therapy Vs. C-IMRT for the Treatment of Upper Thoracic Esophageal Cancer

Purpose: To compare plans using volumetric-modulated arc therapy (VMAT) with conventional sliding window intensity-modulated radiation therapy (c-IMRT) to treat upper thoracic esophageal cancer (EC). Methods: CT datasets of 11 patients with upper thoracic EC were identified. Four plans were generated for each patient: c-IMRT with 5 fields (5F) and VMAT with a single arc (1A), two arcs (2A), or three arcs (3A). The prescribed doses were 64 Gy/32 F for the primary tumor (planning target volume 64, PTV64). The dose-volume histogram data, the number of monitoring units (MUs) and the treatment time (TT) for the different plans were compared. Results: All of the plans generated similar dose distributions for PTVs and organs at risk (OARs), except that the 2A- and 3A-VMAT plans yielded a significantly higher conformity index (CI) than the c-IMRT plan. The CI of the PTV64 was improved by increasing the number of arcs in the VMAT plans. The maximum spinal cord dose and the planning risk volume of the spinal cord dose for the two techniques were similar. The 2A- and 3A-VMAT plans yielded lower mean lung doses and heart V50 than the c-IMRT. The V20 and V30 for the lungs in all of the VMAT plans were lower than those in the c-IMRT plan, at the expense of increasing V5, V10 and V13. The VMAT plan resulted in significant reductions in MUs and TT. Conclusion: The 2A-VMAT plan appeared to spare the lungs from moderate-dose irradiation most effectively of all plans, at the expense of increasing the low-dose irradiation volume, and also significantly reduced the number of required MUs and the TT. The CI of the PTVs and the OARs was improved by increasing the arc-number from 1 to 2. however, no significant improvement was observed using the 3A-VMAT, except for an increase in the TT. This work was sponsored by Shantou University Medical College Clinical Research Enhancement Initiative(NO.201424)

60 APPLIED LIFE SCIENCES↗

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses to achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. 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.

60 APPLIED LIFE SCIENCES↗

SU-F-BRB-07: A Plan Comparison Tool to Ensure Robustness and Deliverability in Online-Adaptive Radiotherapy

Purpose: To develop a plan comparison tool that will ensure robustness and deliverability through analysis of baseline and online-adaptive radiotherapy plans using similarity metrics. Methods: The ViewRay MRIdian treatment planning system allows export of a plan file that contains plan and delivery information. A software tool was developed to read and compare two plans, providing information and metrics to assess their similarity. In addition to performing direct comparisons (e.g. demographics, ROI volumes, number of segments, total beam-on time), the tool computes and presents histograms of derived metrics (e.g. step-and-shoot segment field sizes, segment average leaf gaps). Such metrics were investigated for their ability to predict that an online-adapted plan reasonably similar to a baseline plan where deliverability has already been established. Results: In the realm of online-adaptive planning, comparing ROI volumes offers a sanity check to verify observations found during contouring. Beyond ROI analysis, it has been found that simply editing contours and re-optimizing to adapt treatment can produce a delivery that is substantially different than the baseline plan (e.g. number of segments increased by 31%), with no changes in optimization parameters and only minor changes in anatomy. Currently the tool can quickly identify large omissions or deviations from baseline expectations. As our online-adaptive patient population increases, we will continue to develop and refine quantitative acceptance criteria for adapted plans and relate them historical delivery QA measurements. Conclusion: The plan comparison tool is in clinical use and reports a wide range of comparison metrics, illustrating key differences between two plans. This independent check is accomplished in seconds and can be performed in parallel to other tasks in the online-adaptive workflow. Current use prevents large planning or delivery errors from occurring, and ongoing refinements will lead to increased assurance of plan quality.

60 APPLIED LIFE SCIENCES↗

SU-F-BRB-10: A Statistical Voxel Based Normal Organ Dose Prediction Model for Coplanar and Non-Coplanar Prostate Radiotherapy

Purpose: Knowledge learned from previous plans can be used to guide future treatment planning. Existing knowledge-based treatment planning methods study the correlation between organ geometry and dose volume histogram (DVH), which is a lossy representation of the complete dose distribution. A statistical voxel dose learning (SVDL) model was developed that includes the complete dose volume information. Its accuracy of predicting volumetric-modulated arc therapy (VMAT) and non-coplanar 4π radiotherapy was quantified. SVDL provided more isotropic dose gradients and may improve knowledge-based planning. Methods: 12 prostate SBRT patients originally treated using two full-arc VMAT techniques were re-planned with 4π using 20 intensity-modulated non-coplanar fields to a prescription dose of 40 Gy. The bladder and rectum voxels were binned based on their distances to the PTV. The dose distribution in each bin was resampled by convolving to a Gaussian kernel, resulting in 1000 data points in each bin that predicted the statistical dose information of a voxel with unknown dose in a new patient without triaging information that may be collectively important to a particular patient. We used this method to predict the DVHs, mean and max doses in a leave-one-out cross validation (LOOCV) test and compared its performance against lossy estimators including mean, median, mode, Poisson and Rayleigh of the voxelized dose distributions. Results: SVDL predicted the bladder and rectum doses more accurately than other estimators, giving mean percentile errors ranging from 13.35–19.46%, 4.81–19.47%, 22.49–28.69%, 23.35–30.5%, 21.05–53.93% for predicting mean, max dose, V20, V35, and V40 respectively, to OARs in both planning techniques. The prediction errors were generally lower for 4π than VMAT. Conclusion: By employing all dose volume information in the SVDL model, the OAR doses were more accurately predicted. 4π plans are better suited for knowledge-based planning than the VMAT plans that are strongly biased in its dose gradient orientation. This project is supported by Varian Medical Systems.

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SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address this limitation. Future work will incorporate automated registration between setup images (cone-beam CT and kilovoltage images) for synCT and CT-SIM. Submitting institution holds research agreements with Philips HealthCare, Best, Netherlands and Varian Medical Systems, Palo Alto, CA. Research partially sponsored via an Internal Mentored Research Grant.

60 APPLIED LIFE SCIENCES↗

SU-F-207-01: Comparison of Beam Characteristics and Organ Dose From Four Commercial Multidetector Computed Tomography Scanners

Purpose: To compare dosimetric properties and patient organ doses from four commercial multidetector CT (MDCT) using Monte Carlo (MC) simulation based on the absorbed dose measured using a Farmer chamber and cylindrical water phantoms according to AAPM TG-111. Methods: Four commercial MDCT were modeled using the GMctdospp (IMPS, Germany) based on the EGSnrc user code. The incident photon spectrum and bowtie filter for MC simulations were determined so that calculated values of aluminum half-value layer (Al-HVL) and off-center ratio (OCR) profile in air agreed with measured values. The MC dose was calibrated from absorbed dose measurements using a Farmer chamber and cylindrical water phantoms. The dose distributions of head, chest, and abdominal scan were calculated using patient CT images and mean organ doses were evaluated from dose volume histograms. Results: The HVLs at 120 kVp of Brilliance, LightSpeed, Aquilion, and SOMATOM were 9.1, 7.5, 7.2, and 8.7 mm, respectively. The calculated Al-HVLs agreed with measurements within 0.3%. The calculated and measured OCR profiles agreed within 5%. For adult head scans, mean doses for eye lens from Brilliance, LightSpeed, Aquilion, and SOMATOM were 21.7, 38.5, 47.2 and 28.4 mGy, respectively. For chest scans, mean doses for lung from Brilliance, LightSpeed, Aquilion, and SOMATOM were 21.1, 26.1, 35.3 and 24.0 mGy, respectively. For adult abdominal scans, the mean doses for liver from Brilliance, LightSpeed, Aquilion, and SOMATOM were 16.5, 21.3, 22.7, and 18.0 mGy, respectively. The absorbed doses increased with decreasing Al-HVL. The organ doses from Aquilion were two greater than those from Brilliance in head scan. Conclusion: MC dose distributions based on absorbed dose measurement in cylindrical water phantom are useful to evaluate individual patient organ doses.

60 APPLIED LIFE SCIENCES↗

MO-D-213-05: Sensitivity of Routine IMRT QA Metrics to Couch and Collimator Rotations

Purpose: To assess the sensitivity of gamma index and other IMRT QA metrics to couch and collimator rotations. Methods: Two brain IMRT plans with couch and/or collimator rotations in one or more of the fields were evaluated using the IBA MatriXX ion chamber array and its associated software (OmniPro-I’mRT). The plans were subjected to routine QA by 1) Creating a composite planar dose in the treatment planning system (TPS) with the couch/collimator rotations and 2) Creating the planar dose after “zeroing” the rotations. Plan deliveries to MatriXX were performed with all rotations set to zero on a Varian 21ex linear accelerator. This in effect created TPS-created planar doses with an induced rotation error. Point dose measurements for the delivered plans were also performed in a solid water phantom. Results: The IMRT QA of the plans with couch and collimator rotations showed clear discrepancies in the planar dose and 2D dose profile overlays. The gamma analysis, however, did pass with the criteria of 3%/3mm (for 95% of the points), albeit with a lower percentage pass rate, when one or two of the fields had a rotation. Similar results were obtained with tighter criteria of 2%/2mm. Other QA metrics such as percentage difference or distance-to-agreement (DTA) histograms produced similar results. The point dose measurements did not obviously indicate the error due to location of dose measurement (on the central axis) and the size of the ion chamber used (0.6 cc). Conclusion: Relying on Gamma analysis, percentage difference, or DTA to determine the passing of an IMRT QA may miss critical errors in the plan delivery due to couch/collimator rotations. A combination of analyses for composite QA plans, or per-beam analysis, would detect these errors.

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MO-FG-BRA-01: Development of An Image-Guided Dosimetric Planning System for Injectable Brachytherapy Using ELP Nanoparticles

Purpose: To develop, validate, and evaluate a methodology for determining dosimetry for intratumoral injections of elastin-like-polypeptide (ELP) brachytherapy nanoparticles. These organic-polymer-based nanoparticles are injectable, biodegradable, and genetically tunable. We present a genetically encoded polymer-solution, composed of novel radiolabeled-ELP nanoparticles that are custom-designed to self-assemble into a local source upon intratumoral injection. Our preliminary results of a small animal study demonstrate 100% tumor response, effective radionuclide retention-rates, strong in vivo stability, and no polymer-induced toxicities. While our approach is therefore highly promising for improved brachytherapy, the current workflow lacks a dosimetry framework. Methods: We are developing a robust software framework that provides image-guided dosimetric-planning capabilities for ELP brachytherapy. The user graphically places ELP injection sites within a µCT-planning-image, and independently defines each injection volume, concentration, and radioisotope to be used. The resulting internal dosimetry is then pre-determined by first modeling post-injection ELP advection-diffusion, and then calculating the resulting dose distribution based on a point- dose-kernel-convolution algorithm. We have experimentally measured ELP steady-state concentrations via µSPECT acquisition, and validated our dose calculation algorithm against Monte Carlo simulations of several radioactivity distributions. Finally, we have investigated potential advantages and limitations of various ELP injection parameters. Results: The µSPECT results demonstrated inhomogeneous steady-state distributions of ELP in tissue, and Monte Carlo radioactivity distributions were designed accordingly. Our algorithm yielded a root-mean-square-error of less than 2% for each distribution tested (average root-mean-square-error was 0.73%). Dose-Volume-Histogram analysis of five different plans showed how strategic injection placement, and an injection volume-tapering technique, could be used to achieve D95% target coverage. Conclusion: We have preliminarily developed a novel planning framework for ELP brachytherapy. Its dosimetry accuracy has been validated against Monte Carlo, and we have started to investigate the potential advantages of injection-based planning. This system, once fully developed, will serve as the technical foundation for our novel approach.

60 APPLIED LIFE SCIENCES↗

MO-FG-204-01: Improved Noise Suppression for Dual-Energy CT Through Entropy Minimization

Purpose: In dual energy CT (DECT), noise amplification during signal decomposition significantly limits the utility of basis material images. Since clinically relevant objects contain a limited number of materials, we propose to suppress noise for DECT based on image entropy minimization. An adaptive weighting scheme is employed during noise suppression to improve decomposition accuracy with limited effect on spatial resolution and image texture preservation. Methods: From decomposed images, we first generate a 2D plot of scattered data points, using basis material densities as coordinates. Data points representing the same material generate a highly asymmetric cluster. We orient an axis by minimizing the entropy in a 1D histogram of these points projected onto the axis. To suppress noise, we replace pixel values of decomposed images with center-of-mass values in the direction perpendicular to the optimal axis. To limit errors due to cluster overlap, we weight each data point’s contribution based on its high and low energy CT values and location within the image. The proposed method’s performance is assessed on physical phantom studies. Electron density is used as the quality metric for decomposition accuracy. Our results are compared to those without noise suppression and with a recently developed iterative method. Results: The proposed method reduces noise standard deviations of the decomposed images by at least one order of magnitude. On the Catphan phantom, this method greatly preserves the spatial resolution and texture of the CT images and limits induced error in measured electron density to below 1.2%. In the head phantom study, the proposed method performs the best in retaining fine, intricate structures. Conclusion: The entropy minimization based algorithm with adaptive weighting substantially reduces DECT noise while preserving image spatial resolution and texture. Future investigations will include extensive investigations on material decomposition accuracy that go beyond the current electron density calculations. This work was supported in part by the National Institutes of Health (NIH) under Grant Number R21 EB012700.

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MO-F-CAMPUS-T-05: Correct Or Not to Correct for Rotational Patient Set-Up Errors in Stereotactic Radiosurgery

Purpose: To quantify the effect of patient rotation in stereotactic radiation therapy and establish a threshold where rotational patient set-up errors have a significant impact on target coverage. Methods: To simulate rotational patient set-up errors, a Matlab code was created to rotate the patient dose distribution around the treatment isocentre, located centrally in the lesion, while keeping the structure contours in the original locations on the CT and MRI. Rotations of 1°, 3°, and 5° for each of the pitch, roll, and yaw, as well as simultaneous rotations of 1°, 3°, and 5° around all three axes were applied to two types of brain lesions: brain metastasis and acoustic neuroma. In order to analyze multiple tumour shapes, these plans included small spherical (metastasis), elliptical (acoustic neuroma), and large irregular (metastasis) tumour structures. Dose-volume histograms and planning target volumes were compared between the planned patient positions and those with simulated rotational set-up errors. The RTOG conformity index for patient rotation was also investigated. Results: Examining the tumour volumes that received 80% of the prescription dose in the planned and rotated patient positions showed decreases in prescription dose coverage of up to 2.3%. Conformity indices for treatments with simulated rotational errors showed decreases of up to 3% compared to the original plan. For irregular lesions, degradation of 1% of the target coverage can be seen for rotations as low as 3°. Conclusions: This data shows that for elliptical or spherical targets, rotational patient set-up errors less than 3° around any or all axes do not have a significant impact on the dose delivered to the target volume or the conformity index of the plan. However the same rotational errors would have an impact on plans for irregular tumours.

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MO-G-304-02: Knowledge Based DVH Prediction Using a Geometric Dose Transform

Purpose: To demonstrate a novel method for predicting patient dose-volume histograms (DVHs) using a prior database of optimized radiotherapy treatment plans. Such predicted DVHs could be useful for automating treatment planning. Methods: Our initial demonstration utilized a database of 100 prostate intensity-modulated radiotherapy (IMRT) data-sets. Each data-set contained a CT image with contours of the planning target volume (PTV), rectum, and bladder, the parameters of a clinically approved IMRT plan, and a corresponding simulated dose distribution. We applied a novel geometric transformation to remove the influence of the PTV size, shape, and location on the dose distribution. We termed the transformed distribution the geometrically normalized dose distribution (GNDD). This normalization transform was applied to 80 data-sets randomly selected from the database, and a population GNDD was computed as the average. Next, the population GNDD was mapped onto each of the remaining 20 patient datasets using the reverse of the geometric normalization transform, and predicted DVHs were calculated from the reverse transformed dose distributions (GNDD-DVHs). In addition, a state of the art machine learning based method from the literature was tested for comparison. Results: DVH prediction accuracy was quantified by calculating the relative root mean squared error (rRMSE) on predicted DVHs for the 20 test patients using their known DVHs. For bladder, rectum, and PTV average rRMSEs for the GNDD method were 9.7 ± 4.2%, 13.9 ± 6.0%, and 2.3 ± 0.5% respectively. Prediction results using GNDD were roughly equivalent to that from the machine learning method. Conclusion: We developed a new method for predicting DVH curves from a database of prior patient plans. We demonstrated that our simple approach achieves accuracy comparable to a method using a complicated machine learning based approach.

60 APPLIED LIFE SCIENCES↗

TU-AB-BRA-04: Quantitative Radiomics: Sensitivity of PET Textural Features to Image Acquisition and Reconstruction Parameters Implies the Need for Standards

Purpose: Despite increased use of heterogeneity metrics for PET imaging, standards for metrics such as textural features have yet to be developed. We evaluated the quantitative variability caused by image acquisition and reconstruction parameters on PET textural features. Methods: PET images of the NEMA IQ phantom were simulated with realistic image acquisition noise. 35 features based on intensity histograms (IH), co-occurrence matrices (COM), neighborhood-difference matrices (NDM), and zone-size matrices (ZSM) were evaluated within lesions (13, 17, 22, 28, 33 mm diameter). Variability in metrics across 50 independent images was evaluated as percent difference from mean for three phantom girths (850, 1030, 1200 mm) and two OSEM reconstructions (2 iterations, 28 subsets, 5 mm FWHM filtration vs 6 iterations, 28 subsets, 8.6 mm FWHM filtration). Also, patient sample size to detect a clinical effect of 30% with Bonferroni-corrected α=0.001 and 95% power was estimated. Results: As a class, NDM features demonstrated greatest sensitivity in means (5–50% difference for medium girth and reconstruction comparisons and 10–100% for large girth comparisons). Some IH features (standard deviation, energy, entropy) had variability below 10% for all sensitivity studies, while others (kurtosis, skewness) had variability above 30%. COM and ZSM features had complex sensitivities; correlation, energy, entropy (COM) and zone percentage, short-zone emphasis, zone-size non-uniformity (ZSM) had variability less than 5% while other metrics had differences up to 30%. Trends were similar for sample size estimation; for example, coarseness, contrast, and strength required 12, 38, and 52 patients to detect a 30% effect for the small girth case but 38, 88, and 128 patients in the large girth case. Conclusion: The sensitivity of PET textural features to image acquisition and reconstruction parameters is large and feature-dependent. Standards are needed to ensure that prospective trials which incorporate textural features are properly designed to detect clinical endpoints. Supported by NIH grants R01 CA169072, U01 CA148131, NCI Contract (SAIC-Frederick) 24XS036-004, and a research contract from GE Healthcare.

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TU-AB-BRA-06: Texture Feature Reproducibility Between PET/CT and PET/MR Imaging Modalities

Purpose: Radiomics involves the extraction of texture features from different imaging modalities with the purpose of developing models to predict patient treatment outcomes. The purpose of this study is to investigate texture feature reproducibility across [18F]FDG PET/CT and [18F]FDG PET/MR imaging in patients with primary malignancies. Methods: Twenty five prospective patients with solid tumors underwent clinical [18F]FDG PET/CT scan followed by [18F]FDG PET/MR scans. In all patients the lesions were identified using nuclear medicine reports. The images were co-registered and segmented using an in-house auto-segmentation method. Fifty features, based on the intensity histogram, second and high order matrices, were extracted from the segmented regions from both image data sets. One-way random-effects ANOVA model of the intra-class correlation coefficient (ICC) was used to establish texture feature correlations between both data sets. Results: Fifty features were classified based on their ICC values, which were found in the range from 0.1 to 0.86, in three categories: high, intermediate, and low. Ten features extracted from second and high-order matrices showed large ICC ≥ 0.70. Seventeen features presented intermediate 0.5 ≤ ICC ≤ 0.65 and the remaining twenty three presented low ICC ≤ 0.45. Conclusion: Features with large ICC values could be reliable candidates for quantification as they lead to similar results from both imaging modalities. Features with small ICC indicates a lack of correlation. Therefore, the use of these features as a quantitative measure will lead to different assessments of the same lesion depending on the imaging modality from where they are extracted. This study shows the importance of the need for further investigation and standardization of features across multiple imaging modalities.

60 APPLIED LIFE SCIENCES↗

TU-AB-BRA-10: Prognostic Value of Intra-Radiation Treatment FDG-PET and CT Imaging Features in Locally Advanced Head and Neck Cancer

Purpose: To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC). Methods: 68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit. Results: For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p<0.001). Wavelet coefficients turned out to be the most predictive features. Prediction of distant recurrence showed a similar trend, in which pre-treatment PET features of lymph nodes had the highest AUC of 0.705. Conclusion: The radiomics approach identified novel imaging features that are predictive to radiation treatment response. If prospectively validated in larger cohorts, they could aid in risk-adaptive treatment of HNC.

60 APPLIED LIFE SCIENCES↗

TU-AB-303-08: GPU-Based Software Platform for Efficient Image-Guided Adaptive Radiation Therapy

Purpose: In this study, we develop an integrated software platform for adaptive radiation therapy (ART) that combines fast and accurate image registration, segmentation, and dose computation/accumulation methods. Methods: The proposed system consists of three key components; 1) deformable image registration (DIR), 2) automatic segmentation, and 3) dose computation/accumulation. The computationally intensive modules including DIR and dose computation have been implemented on a graphics processing unit (GPU). All required patient-specific data including the planning CT (pCT) with contours, daily cone-beam CTs, and treatment plan are automatically queried and retrieved from their own databases. To improve the accuracy of DIR between pCT and CBCTs, we use the double force demons DIR algorithm in combination with iterative CBCT intensity correction by local intensity histogram matching. Segmentation of daily CBCT is then obtained by propagating contours from the pCT. Daily dose delivered to the patient is computed on the registered pCT by a GPU-accelerated superposition/convolution algorithm. Finally, computed daily doses are accumulated to show the total delivered dose to date. Results: Since the accuracy of DIR critically affects the quality of the other processes, we first evaluated our DIR method on eight head-and-neck cancer cases and compared its performance. Normalized mutual-information (NMI) and normalized cross-correlation (NCC) computed as similarity measures, and our method produced overall NMI of 0.663 and NCC of 0.987, outperforming conventional methods by 3.8% and 1.9%, respectively. Experimental results show that our registration method is more consistent and roust than existing algorithms, and also computationally efficient. Computation time at each fraction took around one minute (30–50 seconds for registration and 15–25 seconds for dose computation). Conclusion: We developed an integrated GPU-accelerated software platform that enables accurate and efficient DIR, auto-segmentation, and dose computation, thus supporting an efficient ART workflow. This work was supported by NIH/NCI under grant R42CA137886.

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TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.

60 APPLIED LIFE SCIENCES↗

TU-EF-304-12: Proton Radiation Therapy for Left-Sided Breast Cancer: LET and RBE Considerations for Cardiac Toxicity

Purpose: Increased risk of coronary artery disease has been documented for patients treated with radiation for left-sided breast cancer. Proton therapy (PRT) has been shown to significantly decrease cardiac irradiation, however variations in relative biological effectiveness (RBE) have been ignored so far. In this study we evaluate the impact of accounting for RBE variations on sensitive structures located within high linear energy transfer (LET) areas (distal end) of the proton treatment fields, for this treatment site. Methods: Three patients treated in our institution with PRT for left-sided breast cancer were selected. All patients underwent reconstructive surgery after mastectomy and treated to a total dose of 50.4Gy with beam(s) vertical to the chest wall. Dose and LET distributions were calculated using Monte Carlo (MC-TOPAS - TOol for PArticle Simulation). The LET-based, variable-RBE-weighted dose was compared to the analytical calculation algorithm (ACA) and MC dose distributions for a constant RBE of 1.1, based on volume histograms and mean values for the target, heart and left anterior descending coronary artery (LAD). Results: Assuming a constant RBE and compared to the ACA dose, MC predicted lower mean target and heart doses by 0.5% to 2.7% of the prescription dose. For variable RBE, plan evaluation showed increased mean target dose by up to 5%. Mean variable-RBE-weighted doses for the LAD ranged from 2.7 to 5.9Gy(RBE) among patients increased by 41%–64.2% compared to constant RBE ACA calculation (absolute dose: 1.7–3.9Gy(RBE)). Smaller increase in mean heart doses was noticed. Conclusion: ACA overestimates the target mean dose by up to 2.7%. However, disregarding variations in RBE may lead to significant underestimation of the dose to sensitive structures at the distal end of the proton treatment field and could thus impact outcome modeling for cardiac toxicities after proton therapy. These results are subject to RBE model and parameter uncertainties.

60 APPLIED LIFE SCIENCES↗

TU-G-BRD-03: IMRT Dosimetry Differences in An Institution with Community and Academic Model

Purpose: Radiation outcome among institutions can be interpreted meaningfully if the dose delivery and prescription to the target volume is documented accurately and consistently. ICRU-83 recommended specific guidelines in IMRT for target volume definitions and dose reporting. This retrospective study evaluates the pattern of IMRT dose prescription and recording in an academic institution (AI) and a community hospital (CH) models in a single institution with reference to ICRU-83 recommendation. Materials & Methods: Dosimetric information of 625 (500 from academic and 125 from community) patients treated with IMRT was collected retrospectively from the AI and a CH. The dose-volume histogram (DVH) for the target volume of each patient was extracted. Standard dose parameters such as D2, D50, D95, D98, D100, as well as the homogeneity index (HI) defined as (D2-D98)/D50 and monitor units (MUs) were collected. Results: Significant dosimetric variations were observed in disease sites and between AI and CH. The variation in the mean value of D95 for AI is 98.48±4.12 and for CH is 96.41±4.13. A similar pattern was noticed for D50 (104.18±6.04 for AI and 101.05±3.49 for CH). Thus, nearly 95% of patients received dosage higher than 100% to the site viewed by D50 and varied between AI and CH models. The average variation of HI is found to be 0.12±0.08 and 0.11±0.08 for AI and CH model, showing better IMRT treatment plans for academic model compared to community. Conclusion: Even with the implementation of ICRU-83 guidelines, there is a large variation in dose prescription and delivery in IMRT. The variation is institution and site specific. For any meaningful comparison of the IMRT outcome, strict guidelines for dose reporting should be maintained in every institution.

60 APPLIED LIFE SCIENCES↗