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SU-D-207B-01: Radiomics Feature Reproducibility From Repeat CT Scans of Patients with Rectal Cancer

Purpose: To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Methods: 40 rectal cancer patients were enrolled in this study, each of whom underwent two CT scans within average 8.7 days (5 days to 17 days), before any treatment was delivered. The rectal gross tumor volume (GTV) was distinguished and segmented by an experienced oncologist in both CTs. Totally, more than 2000 radiomics features were defined in this study, which were divided into four groups (I: GLCM, II: GLRLM III: Wavelet GLCM and IV: Wavelet GLRLM). For each group, five types of features were extracted (Max slice: features from the largest slice of target images, Max value: features from all slices of target images and choose the maximum value, Min value: minimum value of features for all slices, Average value: average value of features for all slices, Matrix sum: all slices of target images translate into GLCM and GLRLM matrices and superpose all matrices, then extract features from the superposed matrix). Meanwhile a LOG (Laplace of Gauss) filter with different parameters was applied to these images. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) were calculated to assess the reproducibility. Results: 403 radiomics features were extracted from each type of patients’ medical images. Features of average type are the most reproducible. Different filters have little effect for radiomics features. For the average type features, 253 out of 403 features (62.8%) showed high reproducibility (ICC≥0.8), 133 out of 403 features (33.0%) showed medium reproducibility (0.8≥ICC≥0.5) and 17 out of 403 features (4.2%) showed low reproducibility (ICC≥0.5). Conclusion: The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction.

60 APPLIED LIFE SCIENCES↗

SU-F-R-52: A Comparison of the Performance of Radiomic Features From Free Breathing and 4DCT Scans in Predicting Disease Recurrence in Lung Cancer SBRT Patients

Purpose: There is a clinical need to identify patients who are at highest risk of recurrence after being treated with stereotactic body radiation therapy (SBRT). Radiomics offers a non-invasive approach by extracting quantitative features from medical images based on tumor phenotype that is predictive of an outcome. Lung cancer patients treated with SBRT routinely undergo free breathing (FB image) and 4DCT (average intensity projection (AIP) image) scans for treatment planning to account for organ motion. The aim of the current study is to evaluate and compare the prognostic performance of radiomic features extracted from FB and AIP images in lung cancer patients treated with SBRT to identify which image type would generate an optimal predictive model for recurrence. Methods: FB and AIP images of 113 Stage I-II NSCLC patients treated with SBRT were analysed. The prognostic performance of radiomic features for distant metastasis (DM) was evaluated by their concordance index (CI). Radiomic features were compared with conventional imaging metrics (e.g. diameter). All p-values were corrected for multiple testing using the false discovery rate. Results: All patients received SBRT and 20.4% of patients developed DM. From each image type (FB or AIP), nineteen radiomic features were selected based on stability and variance. Both image types had five common and fourteen different radiomic features. One FB (CI=0.70) and five AIP (CI range=0.65–0.68) radiomic features were significantly prognostic for DM (p<0.05). None of the conventional features derived from FB images (range CI=0.60–0.61) were significant but all AIP conventional features were (range CI=0.64–0.66). Conclusion: Features extracted from different types of CT scans have varying prognostic performances. AIP images contain more prognostic radiomic features for DM than FB images. These methods can provide personalized medicine approaches at low cost, as FB and AIP data are readily available within a large number of radiation oncology departments. R.M. had consulting interest with Amgen (ended in 2015).

60 APPLIED LIFE SCIENCES↗

SU-F-J-62: Assessment of Dose Changes Due to Anterior-Posterior Patient Separation During Daily MVCT Scans

Purpose: To determine the effects of patient separation on absolute dose and dose distribution in patients undergoing pelvic radiotherapy on TomoTherapy. Methods: An Alderson RANDO phantom with 4cm of bolus was imaged on a CT simulator and the resulting scans were contoured as a whole pelvic case. Using TomoTherapy Planning Station, the plan was designed to give 45 Gy to 95% of the treatment volume in 25 fractions. TomoTherapy MVCT scans were performed on the RANDO phantom with 2cm and 4cm of bolus removed to simulate visible changes in a patient’s anatomy. The MVCT images were rigidly registered with planning CT images on TomoTherapy Planned Adaptive. The original fluence was recalculated on the MVCT images and changes in dose distribution due to patient separation were quantified by the changes in DVHs for the target volume and the organs at risk. Results: Patient separation difference equivalent to 2cm and 4cm in anterior-posterior direction resulted in an increase of the PTV D50 and maximum PTV dose of 5.6%, 6.2% for 2cm and 7.7%, 10.4% for 4cm, respectively. For the 2cm change, D50 and maximum doses to organs at risk increased by 6.5%, 7.1% in the bladder, 4.9%, 4.8% in the rectum, and 5.3%, 6.6% in the bowel. For the 4cm change, D50 and maximum doses increased by 10.7%, 12.2% in the bladder, 5.9%, 6.1% in the rectum, and 7.7%, 10.1% in the bowel. Conclusion: This research indicates that, without any changes to the structures, patient separation in the anterior-posterior direction can affect the dose distribution for the PTV and organs at risk. These results can assist physicians in determining if obtaining a new CT simulation set and replanning is necessary for pelvic patients on TomoTherapy.

60 APPLIED LIFE SCIENCES↗

SU-F-J-223: Patterns of Failure for Laryngeal Cancer Patients Treated with Definitive IMRT: Comparing Two Different Methods for Determining the Origin of Recurrence From Follow-Up PET/CT Scans

Purpose: To determine patterns of failure in laryngeal cancer treated with definitive IMRT by comparing two different methods for identifying the recurrence epicenter on follow-up PET/CT. Methods: We identified 20 patients treated for laryngeal squamous cell carcinoma with definitive IMRT who had loco-regional recurrence diagnosed on PET/CT. Recurrence PET/CT scans were co-registered with the original treatment planning CT using deformable image registration with the VoxAlign deformation engine in MIM Software. Recurrence volumes were delineated on co-registered follow-up scans using a semi-automatic PETedge tool and two separate methods were used to identify the recurrence point of origin: a) Finding the point within the recurrence volume for which the maximum distance to the surface of the surrounding recurrence volume is smaller than for any other point. b) Finding the point within the recurrence volume with the maximum standardized uptake value (SUVmax), without geometric restrictions.For each method the failure pattern was determined as whether the recurrence origin fell within the original high-dose target volumes GTV70, CTV70, PTV70 (receiving 70Gy), intermediate-risk PTV59 (receiving 59.4Gy) or low-risk PTV54 (receiving 54.1Gy), in the original treatment planning CT. Results: 23 primary/nodal recurrences from the 20 patients were analyzed. The three-dimensional distance between the two different origins was on average 10.5mm (std.dev. 10mm). Most recurrences originated in the high-dose target volumes for both methods with 13 (57%) and 11 (48%) in the GTV70 and 20 (87%) and 20 (87%) in the PTV70 for method a) and b), respectively. There was good agreement between the two methods in classifying the origin target volumes with 69% concordance for GTV70, 89% for CTV70 and 100% for PTV70. Conclusion: With strong agreement in patterns of failure between two separate methods for determining recurrence origin, we conclude that most recurrences occurred within the high-dose treatment region, which influences potential risk-adaptive treatment strategies.

60 APPLIED LIFE SCIENCES↗

SU-F-T-158: Experimental Characterization of Field Size Dependence of Dose and Lateral Beam Profiles of Scanning Proton and Carbon Ion Beams for Empirical Model in Air

Purpose: The Gaussian model for the lateral profiles in air is crucial for an accurate treatment planning system. The field size dependence of dose and the lateral beam profiles of scanning proton and carbon ion beams are due mainly to particles undergoing multiple Coulomb scattering in the beam line components and secondary particles produced by nuclear interactions in the target, both of which depend upon the energy and species of the beam. In this work, lateral profile shape parameters were fitted to measurements of field size dependence dose at the center of field size in air. Methods: Previous studies have employed empirical fits to measured profile data to significantly reduce the QA time required for measurements. From this approach to derive the weight and sigma of lateral profiles in air, empirical model formulations were simulated for three selected energies for both proton and carbon beams. Results: The 20%–80% lateral penumbras predicted by the double model for proton and single model for carbon with the error functions agreed with the measurements within 1 mm. The standard deviation between measured and fitted field size dependence of dose for empirical model in air has a maximum accuracy of 0.74% for proton with double Gaussian, and of 0.57% for carbon with single Gaussian. Conclusion: We have demonstrated that the double Gaussian model of lateral beam profiles is significantly better than the single Gaussian model for proton while a single Gaussian model is sufficient for carbon. The empirical equation may be used to double check the separately obtained model that is currently used by the planning system. The empirical model in air for dose of spot scanning proton and carbon ion beams cannot be directly used for irregular shaped patient fields, but can be to provide reference values for clinical use and quality assurance.

60 APPLIED LIFE SCIENCES↗

SU-F-T-162: Comparison of Beam Data for Two Varian ProBeam Pencil Beam Scanning Proton Systems

Purpose: To compare the beam data for proton spot scanning beams for the first two Varian ProBeam sites in the US at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (Scripps). To investigate how well beams can be matched between rooms. Method: Beam data were acquired with independent dosimetry systems and compared for two sites. Integrated depth dose curves (IDDs) were acquired with large volume PTW Bragg peak chambers in a 3D water tank for pencil beams at both sites. Spot profiles were acquired at different distances from the isocenter at a gantry angle of 0 degrees as well as function of gantry angle. Results: IDDs for the two Varian ProBeam proton sites are similar, except in the plateau region were the Scripps data is on average 4.5% higher relative to each other, but only 1.5% relative to the maximum at the Bragg Peak. This increase in the plateau region decrease as energy increase and for energies larger than 180 MeV there is no marked difference. Range in water coincide for all energies within 0.5mm. The sigma of the spot profiles in air are within 10% of each other at isocenter. This difference increase as the detector distance from the isocenter is increased. Conclusion: Beam data of the Varian ProBeam proton spot scanning beams for two sites are very well matched. Differences will not be clinically relevant.

60 APPLIED LIFE SCIENCES↗

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D{sub 5}/D{sub 95}) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

60 APPLIED LIFE SCIENCES↗

SU-F-T-190: Homogeneity Study of Proton and Heavy Ion Scanning Beams Based On Different Compositions of Spot Sizes (FWHM) and Grid Sizes

Purpose: Different particle scanning beam delivery systems have different delivery accuracies. This study was performed to determine, for our particle treatment system, an appropriate composition (n=FWHM/GS) of spot size(FWHM) and grid size (GS), which can provide homogenous delivered dose distributions for both proton and heavy ion scanning beam radiotherapy. Methods: We analyzed the delivery errors of our beam delivery system using log files from the treatment of 28 patients. We used a homemade program to simulate square fields for different n values with and without considering the delivery errors and analyzed the homogeneity. All spots were located on a rectilinear grid with equal spacing in the × and y directions. After that, we selected 7 energy levels for both proton and carbon ions. For each energy level, we made 6 square field plans with different n values (1, 1.5, 2, 2.5, 3, 3.5). Then we delivered those plans and used films to measure the homogeneity of each field. Results: For program simulation without delivery errors, when n≥1.1 the homogeneity can be within ±3%. For both proton and carbon program simulations with delivery errors and film measurements, the homogeneity can be within ±3% when n≥2.5. Conclusion: For our facility with system errors, the n≥2.5 is appropriate for maintaining homogeneity within ±3%.

60 APPLIED LIFE SCIENCES↗

SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33 fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric levels for patients with base of tongue cancer.

60 APPLIED LIFE SCIENCES↗

SU-F-T-217: A Comprehensive Monte-Carlo Study of Out-Of-Field Secondary Neutron Spectra in a Scanned-Beam Proton Therapy Treatment Room

Purpose: To simulate secondary neutron radiation-fields produced at different positions during phantom irradiation inside a scanning proton therapy gantry treatment room. Further, to identify origin, energy distribution and angular emission as function of proton beam energy. Methods: GEANT4 and FLUKA Monte-Carlo codes were used to model the relevant parts of the treatment room in a gantry-equipped pencil beam scanning proton therapy facility including walls, floor, metallic gantry-components, patient table and the homogeneous PMMA target. The proton beams were modeled based on experimental beam ranges in water and spot shapes in air. Neutron energy spectra were simulated at 0°, 45°, 90° and 135° relative to the beam axis at 2m distance from isocenter, as well as 11×11 cm2 fields for 75MeV, 140MeV, 200MeV and for 118MeV with 5cm PMMA range-shifter. The total neutron energy distribution was recorded for these four positions and proton energies. Additionally, the room-components generating secondary neutrons in the room and their contributions to the total spectrum were identified and quantified. Results: FLUKA and GEANT4 simulated neutron spectra showed good general agreement in the whole energy range of 10{sup −}9 to 10{sup 2} MeV. Comparison of measured spectra with the simulated contributions of the various room components helped to limit the complexity of the room model, by identifying the dominant contributions to the secondary neutron spectrum. The iron of the bending magnet and counterweight were identified as sources of secondary evaporation-neutrons, which were lacking in simplified room models. Conclusion: Thorough Monte-Carlo simulations have been performed to complement Bonner-sphere spectrometry measurements of secondary neutrons in a clinical proton therapy treatment room. Such calculations helped disentangling the origin of secondary neutrons and their dominant contributions to measured spectra, besides providing a useful validation of widely used Monte-Carlo packages in comparison to experimental data. Cluster of Excellence of the German Research Foundation (DFG) “Munich-Centre for Advanced Photonics (MAP)”.

60 APPLIED LIFE SCIENCES↗

SU-G-JeP2-07: Fusion Optimization of Multi-Contrast MRI Scans for MR-Based Treatment Planning

Purpose: To develop an image fusion method using multiple contrast MRI scans for MR-based treatment planning. Methods: T1 weighted (T1-w), T2 weighted (T2-w) and diffusion weighted images (DWI) were acquired from liver cancer patient with breath-holding. Image fade correction and deformable image registration were performed using VelocityAI (Varian Medical Systems, CA). Registered images were normalized to mean voxel intensity for each image dataset. Contrast to noise ratio (CNR) between tumor and liver was quantified. Tumor area was defined as the GTV contoured by physicians. Normal liver area with equivalent dimension was used as background. Noise was defined by the standard deviation of voxel intensities in the same liver area. Linear weightings were applied to T1-w, T2-w and DWI images to generate composite image and CNR was calculated for each composite image. Optimization process were performed to achieve different clinical goals. Results: With a goal of maximizing tumor contrast, the composite image achieved a 7–12 fold increase in tumor CNR (142.8 vs. −2.3, 11.4 and 20.6 for T1-w, T2-w and DWI only, respectively), while anatomical details were largely invisible. With a weighting combination of 100%, −10% and −10%, respectively, tumor contrast was enhanced from −2.3 to −5.4, while the anatomical details were clear. With a weighting combination of 25%, 20% and 55%, balanced tumor contrast and anatomy was achieved. Conclusion: We have investigated the feasibility of performing image fusion optimization on multiple contrast MRI images. This mechanism could help utilize multiple contrast MRI scans to potentially facilitate future MR-based treatment planning.

60 APPLIED LIFE SCIENCES↗

SU-G-IeP3-08: Image Reconstruction for Scanning Imaging System Based On Shape-Modulated Point Spreading Function

Purpose: Deconvolution is a widely used tool in the field of image reconstruction algorithm when the linear imaging system has been blurred by the imperfect system transfer function. However, due to the nature of Gaussian-liked distribution for point spread function (PSF), the components with coherent high frequency in the image are hard to restored in most of the previous scanning imaging system, even the relatively accurate PSF is acquired. We propose a novel method for deconvolution of images which are obtained by using shape-modulated PSF. Methods: We use two different types of PSF - Gaussian shape and donut shape - to convolute the original image in order to simulate the process of scanning imaging. By employing deconvolution of the two images with corresponding given priors, the image quality of the deblurred images are compared. Then we find the critical size of the donut shape compared with the Gaussian shape which has similar deconvolution results. Through calculation of tightened focusing process using radially polarized beam, such size of donut is achievable under same conditions. Results: The effects of different relative size of donut and Gaussian shapes are investigated. When the full width at half maximum (FWHM) ratio of donut and Gaussian shape is set about 1.83, similar resolution results are obtained through our deconvolution method. Decreasing the size of donut will favor the deconvolution method. A mask with both amplitude and phase modulation is used to create a donut-shaped PSF compared with the non-modulated Gaussian PSF. Donut with size smaller than our critical value is obtained. Conclusion: The utility of donutshaped PSF are proved useful and achievable in the imaging and deconvolution processing, which is expected to have potential practical applications in high resolution imaging for biological samples.

60 APPLIED LIFE SCIENCES↗

SU-G-JeP4-09: Impact of Interfractional Motion On Hypofractionated Pencil Beam Scanning Proton Therapy for Prostate Cancer

Purpose: To investigate the impact of anatomy/setup variations on standard vs. hypofractionated anterolateral pencil beam scanning (PBS) proton therapy for prostate cancer. Methods: Six prostate cancer patients treated with double-scattering proton therapy, who underwent weekly verification CT scans were selected. Implanted fiducials were used for localization, and endorectal balloons for immobilization. New PBS plans using combination of lateral and anterior-oblique (AO) (±35 deg) beams were created. AO beams were added to spare the femoral heads during hypofractionation. Lateral beams delivered 50.4 Gy(RBE) to prostate plus 5-15mm of seminal vesicles and AO beams 28.8 Gy(RBE) to prostate, in 44 fractions. PTV was laterally expanded by 2.5% to account for range uncertainty. No range margins were applied for AO beams, assuming delivery with in-vivo range verification. Field-specific apertures with 1.2cm margin were used. Spot size was ∼9.5mm sigma for 172MeV @isocenter in air. Plans were optimized as single-field-uniform-dose with ∼5% maximum non-uniformity. The planned dose was recomputed on each weekly CT after aligning the fiducials with the simulation CT, scaled and accumulated via deformable image registration. Hypofractionated treatments with 12 and 5 fractions were considered. Equivalent doses were calculated for prostate (α/β= 1.5Gy), bladder and rectum (α/β= 3Gy). Results: The biological equivalent prostate dose was 86.2 and 92.9 Gyeq for the hypofractionation scenarios at 4.32 and 7.35 Gy/fx, respectively. The equivalent prostate D98 was degraded by on average 2.7 Gyeq for standard, and 3.1 and 4.0 Gyeq for the hypofractionated plans after accumulation. Differences between accumulated and planned Dmean/D2/EUD were generally reduced when reducing the number of fractions for bladder and rectum. The average Dmean/D2/EUD differences over all patients and organs-at-risk were 0.74/4.0/9.23, 0.49/3.64/5.51, 0.37/3.21/3.49 Gyeq for 44, 12 and 5 fractions. Conclusion: Hypofractionation makes proton therapy of prostate more susceptible to interfractional motion-induced target dose degradation compared to the standard fractionation.

60 APPLIED LIFE SCIENCES↗

TU-FG-BRB-12: Real-Time Visualization of Discrete Spot Scanning Proton Therapy Beam for Quality Assurance

Purpose: With the growing adoption of proton beam therapy there is an increasing need for effective and user-friendly tools for performing quality assurance (QA) measurements. The speed and versatility of spot-scanning proton beam (PB) therapy systems present unique challenges for traditional QA tools. To address these challenges a proof-of-concept system was developed to visualize, in real-time, the delivery of individual spots from a spot-scanning PB in order to perform QA measurements. Methods: The PB is directed toward a custom phantom with planar faces coated with a radioluminescent phosphor (Gd2O2s:Tb). As the proton beam passes through the phantom visible light is emitted from the coating and collected by a nearby CMOS camera. The images are processed to determine the locations at which the beam impinges on each face of the phantom. By so doing, the location of each beam can be determined relative to the phantom. The cameras are also used to capture images of the laser alignment system. The phantom contains x-ray fiducials so that it can be easily located with kV imagers. Using this data several quality assurance parameters can be evaluated. Results: The proof-of-concept system was able to visualize discrete PB spots with energies ranging from 70 MeV to 220 MeV. Images were obtained with integration times ranging from 20 to 0.019 milliseconds. If not limited by data transmission, this would correspond to a frame rate of 52,000 fps. Such frame rates enabled visualization of individual spots in real time. Spot locations were found to be highly correlated (R{sup 2}=0.99) with the nozzle-mounted spot position monitor indicating excellent spot positioning accuracy Conclusion: The system was shown to be capable of imaging individual spots for all clinical beam energies. Future development will focus on extending the image processing software to provide automated results for a variety of QA tests.

60 APPLIED LIFE SCIENCES↗

TH-CD-209-02: Beam Angle Optimization Incorporating Anatomical Heterogeneities for Pencil Beam Scanning Charged-Particle Therapy

Purpose: In charged particle therapy with pencil beam scanning (PBS), localization of the dose in the Bragg peak makes dose distributions sensitive to lateral tissue heterogeneities. Sensitivity of a PBS plan to lateral tissue heterogeneity can be reduced by selecting suitable beam angles. The purpose of this study is to establish a fast and accurate method of beam angle selection for PBS. Methods: The lateral tissue heterogeneity surrounding the path of respective pencil beams at a given angle was quantified with the heterogeneity number using effective density data of patients. To shorten the computation time, one dimensional dose calculation and optimization were conducted along the central axis of pencil beams originating from the scanning magnets. Calculation was performed for all fields with possible gantry and couch angles. The angles leading the minimum mean heterogeneity number was selected as the optimal beam angle. Three head and neck (H&N) cancer patients were used to evaluate our method. Dose distributions and their robustness to range and set up errors were evaluated for all tested angles, and their relation to their heterogeneity numbers were investigated. Results: Variety of heterogeneity number was clearly shown due to air cavities and bony structures in the patients. The mean value of heterogeneity number in all possible fields varied between 1.2 and 10.6 mm. By selecting a field with a lower mean value of heterogeneity number, target dose coverage and robustness of the fields were improved. Conclusion: We developed a computational method to determine a beam angle that leads good target coverage and robustness to setup errors. The developed stand-alone computation program is simple, fast, accurate and applicable for beam angle selection in PBS therapy.

60 APPLIED LIFE SCIENCES↗

TH-CD-209-12: Spatial Mapping of Scanned Proton Biologic Effect Using the High-Throughput Technique, Continued

Purpose: To investigate the biologic effects of scanned protons by evenly sampling dose-averaged LET (LETd) values. Methods: Our previous high-throughput clonogenic study demonstrated a distinct relationship between RBE and LETd. However, our initial experimental design resulted in over-sampling the low LETd values in the plateau region of the Bragg curve while under-sampling in the region proximal to the Bragg peak as well as the high LETd values in the distal edge of the Bragg curve. To further examine the relationship between RBE and LETd, we refined the experimental design to more evenly sample proton LETd values from 1 to 20 keV/µm by optimizing the thicknesses of the irradiation jig steps. We used the clonogenic survival as the biological endpoint for the H460 lung cancer cell line cultured in 96-well plates (12 columns by 8 rows). In the irradiation, the 8 wells in each column received a uniform dose-LETd pair. The dose-LETd pairs of the 12 different columns were sampled along the Bragg curve of 81.4 MeV scanned protons. Five peak dose levels from 1.5 Gy to 7.5 Gy were delivered with an increment of 1.5 Gy in the preliminary test. Two 96-well plates were irradiated simultaneously to decrease the statistical uncertainties. Results: In the proximal region, for LETd = 5 keV/µm and 8 keV/µm, we did not observe any distinct differential biologic effects between the survival curves. At the Bragg peak (LETd = 9.5 keV/µm) and in the distal edge, irradiation with increasing LET values resulted in decreasing cell survival. Conclusion: The survival curves from the new experimental design support our previous findings that below 10 keV/µm, the LET effect in cell kill is obscured, but above 10 keV/µm, the biologic effects increase with LETd. Funding Support: U19 CA021239-35 and R21 CA187484-01.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 07: A mould room in a box – 3D scanning and printing technology in the radiotherapy clinic

Purpose: We describe the process by which our centre is currently implementing 3D printing and scanning technology for treatment accessory fabrication. This technology can increase efficiency and accuracy of accessory design, production and placement during daily use. Methods: A low-cost 3D printer and 3D optical scanner have been purchased and are being commissioned for clinical use. Commissioning includes assessing: the accuracy of the 3D scanner through comparison with high resolution CT images; the dosimetric characteristics of polylactic acid (PLA) for electron beams; the clinical utility of the technology, and; methods for quality assurance. Results: The agreement between meshes generated using the 3D scanner and CT data was within 2 millimeters for an anthropomorphic head phantom. In terms of electron beam attenuation, 1 centimetre of printed PLA was found equivalent to 1.17 cm of water. In proof-of-concept tests, several types of treatment accessories have been prototyped to date that will benefit from this technology. These include electron and photon bolus for areas with complex surface contours including the ear for electron treatments, the extremities for photon treatments and lead shielding for orthovoltage treatments. Imaging with CT and x-ray showed minimal defects, which will have no significant clinical impact. Geometric fidelity and fit to volunteers and patients was found to be excellent. Conclusions: 3D Printing and scanning can increase efficiency in the clinic for treatments requiring custom accessories. Customized boluses and shielding had excellent fit and reduced uncertainty in positioning.

60 APPLIED LIFE SCIENCES↗

Near-Optimal and Practical Algorithms for Graph Scan Statistics with Connectivity Constraints

One fundamental task in network analysis is detecting “hotspots” or “anomalies” in the network; that is, detecting subgraphs where there is significantly more activity than one would expect given historical data or some baseline process. Scan statistics is one popular approach used for anomalous subgraph detection. This methodology involves maximizing a score function over all connected subgraphs, which is a challenging computational problem. A number of heuristics have been proposed for these problems, but they do not provide any quality guarantees. Here, we propose a framework for designing algorithms for optimizing a large class of scan statistics for networks, subject to connectivity constraints. Our algorithms run in time that scales linearly on the size of the graph and depends on a parameter we call the “effective solution size,” while providing rigorous approximation guarantees. In contrast, most prior methods have super-linear running times in terms of graph size. Extensive empirical evidence demonstrates the effectiveness and efficiency of our proposed algorithms in comparison with state-of-the-art methods. Our approach improves on the performance relative to all prior methods, giving up to over 25% increase in the score. Further, our algorithms scale to networks with up to a million nodes, which is 1–2 orders of magnitude larger than all prior applications.

97 MATHEMATICS AND COMPUTING↗