Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice. The important concepts are then described and how they have been or could be implemented are discussed. Impediments to progress in the collection and use of sufficient quantities of data are also described. Finally, recommendations for how the community can move forward to achieve the potential of big data in radiation oncology are provided.

Implementation of talairach atlas based automated brain segmentation for radiation therapy dosimetry.

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.

Effect of multileaf collimator leaf width on physical dose distributions in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy.

The purpose of this work is to examine physical radiation dose differences between two multileaf collimator (MLC) leaf widths (5 and 10 mm) in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy (IMRT). Three clinical patients with CNS tumors were planned with two different MLC leaf sizes, 5 and 10 mm, representing Varian-120 and Varian-80 Millennium multileaf collimators, respectively. Two sets of IMRT treatment plans were developed. The goal of the first set was radiation dose conformality in three dimensions. The goal for the second set was organ avoidance of a nearby critical structure while maintaining adequate coverage of the target volume. Treatment planning utilized the CadPlan/Helios system (Varian Medical Systems, Milpitas CA) for dynamic MLC treatment delivery. All beam parameters and optimization (cost function) parameters were identical for the 5 and 10 mm plans. For all cases the number of beams, gantry positions, and table positions were taken from clinically treated three-dimensional conformal radiotherapy plans. Conformality was measured by the ratio of the planning isodose volume to the target volume. Organ avoidance was measured by the volume of the critical structure receiving greater than 90% of the prescription dose (V(90)). For three patients with squamous cell carcinoma of the head and neck (T2-T4 N0-N2c M0) 5 and 10 mm leaf widths were compared for parotid preservation utilizing nine coplanar equally spaced beams delivering a simultaneous integrated boost. Because modest differences in physical dose to the parotid were detected, a NTCP model based upon the clinical parameters of Eisbruch et al. was then used for comparisons. The conformality improved in all three CNS cases for the 5 mm plans compared to the 10 mm plans. For the organ avoidance plans, V(90) also improved in two of the three cases when the 5 mm leaf width was utilized for IMRT treatment delivery. In the third case, both the 5 and 10 mm plans were able to spare the critical structure with none of the structure receiving more than 90% of the prescription dose, but in the moderate dose range, less dose was delivered to the critical structure with the 5 mm plan. For the head and neck cases both the 5 and 10 x 2.5 mm beamlets dMLC sliding window techniques spared the contralateral parotid gland while maintaining target volume coverage. The mean parotid dose was modestly lower with the smaller beamlet size (21.04 Gy v 22.36 Gy). The resulting average NTCP values were 13.72% for 10 mm dMLC and 8.24% for 5 mm dMLC. In conclusion, five mm leaf width results in an improvement in physical dose distribution over 10 mm leaf width that may be clinically relevant in some cases. These differences may be most pronounced for single fraction radiosurgery or in cases where the tolerance of the sensitive organ is less than or close to the target volume prescription.

Beam-commissioning methodology for a three-dimensional convolution/superposition photon dose algorithm.

Commissioning beam data for the convolution/superposition dose-calculation algorithm used in a commercial three-dimensional radiation treatment planning (3D RTP) system (PINNACLE(3), ADAC Laboratories, Milpitas, CA) can be difficult and time consuming. Sixteen adjustable parameters, as well as spectral weights representing a discrete energy spectrum, must be fit to sets of central-axis depth doses and off-axis profiles for a large number of field sizes. This paper presents the beam-commissioning methodology that we used to generate accurate beam models. The methodology is relatively rapid and provides physically reasonable values for beam parameters. The methodology was initiated by using vendor-provided automodeling software to generate a single set of beam parameters that gives an approximate fit to relative dose distributions for all beams, open and wedged, in a data set. A limited number of beam parameters were adjusted by small amounts to give accurate beam models for four open-beam field sizes and three wedged-beam field sizes. Beam parameters for other field sizes were interpolated and validated against measured beam data. Using this methodology, a complete set of beam parameters for a single energy can be generated and validated in approximately 40 h. The resulting parameter values yielded calculated relative doses that matched measured relative doses in a water phantom to within 0.5-1.0% along the central axis and 2% along off-axis beam profiles for field sizes from 4 cmx4 cm to the largest field size available. While the methodology presented is specific to the ADAC PINNACLE(3) treatment planning system, the approach should apply to other implementations of the dose model in other treatment planning system.

MO-A-211-01: Volumetric Modulated Arc Therapy.

Volumetric Modulated Arc Therapy (VMAT) is a rotational approach to the delivery of intensity modulated radiation therapy (IMRT) that can be delivered on a conventional linear accelerator. VMAT combines the dosimetric advantages of rotational delivery with the dose painting capabilities of IMRT. In recent years, VMAT has become a widely adopted clinical tool due to the conformal nature of the dose distributions and the efficiency of VMAT delivery. In this session, we will provide an overview of the VMAT delivery technique and will describe recommended steps for starting a VMAT program including VMAT commissioning. We will discuss tips and tricks for the use of VMAT for key clinical sites such as head-and-neck and prostate. Additionally, we will detail the role of VMAT for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). More advanced VMAT topics will also be discussed such as flattening filter free VMAT, gated VMAT, and the use of couch rotations during VMAT delivery. LEARNING OBJECTIVES: 1. Describe volumetric modulated arc therapy (VMAT). 2. Describe commissioning of a VMAT delivery system. 3. Summarize the key elements of starting a VMAT program. 4. Review patient- and machine-specific VMAT quality assurance. 5. Survey VMAT treatment planning systems and planning techniques. 6. Describe advanced VMAT techniques such as gated VMAT and flattening filter free VMAT. CONFLICT OF INTEREST: Richard Popple has a sponsored research agreement with Varian. David Shepard has a sponsored research agreement with Elekta.

SU-E-T-631: Beam Geometry Selection Using Sequential Beam Addition.

PURPOSE: To investigate a beam geometry selection algorithm based on sequential addition of beams. METHODS: The sequential beam addition algorithm (SBA) requires an objective function (score) and a set of candidate beam geometries (pool). The optimal score is determined for each beam in the pool and the best beam selected. Scores are then calculated for the selected beam in combination with each member of the pool. The pair with the best score is selected and the score again determined in combination with each beam in the pool. The process is repeated until the desired number of beams is reached. We selected 3 treatment sites, breast, lung, and brain, and determined beam arrangements for up to 11 beams from a pool comprised of 25 equi-angular transverse beams. For the brain, arrangements were additionally selected from a pool of 22 non-coplanar beams. Scores were determined for geometries comprised of equi-angular transverse beams (EQA), as well as two tangential beams for the breast case. RESULTS: In all cases, SBA resulted in scores superior to EQA. The breast case had the strongest dependence on beam geometry, for which only 7 beam EQA had a score better than the tangential beams, whereas all SBA geometries with more than two beams were superior. For the lung case, for both EQA and SBA the scores monotonically improved with increasing number of beams; however, SBA required fewer beams to achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool was equivalent to EQA, while the non-coplanar pool resulted in slightly better scores; however, the dose-volume histograms demonstrated that the differences were not clinically significant. CONCLUSIONS: For situations in which beam geometry has a significant effect on the objective function, SBA can identify arrangements equivalent to equi-angular geometries but using fewer beams. Varian Medical Systems.

SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

PURPOSE: To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. METHODS: IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. RESULTS: For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. CONCLUSION: AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning.

TU-E-BRB-11: End-To-End Positioning Quality Assurance for Image-Guided Radiosurgery of Multiple Targets Using a Single-Isocenter.

PURPOSE: Using a single isocenter significantly reduces delivery times in radiosurgery involving multiple targets. However, because not every target can be placed at isocenter with this type of treatment, a conventional Winston-Lutz test cannot be used. We describe a novel Winston-Lutz like mulitarget test (MTT) for verifying accurate positioning. METHODS: A target phantom, comprised of an acrylic plate with recesses for three 3/4″ spheres was constructed and a high-resolution (0.5×0.5×0.8 mm) CT scan obtained with PTFE spheres placed in the recesses. The scan was imported into a commercial treatment planning system and multiple beams were prepared, having their isocenter at the centroid of the arrangement of spheres. Every beam incorporated three MLC-defined rectangular apertures that circumscribed the spheres. Custom software selected setup parameters (table, gantry and collimator angle, MLC openings) such that the spheres were centered as precisely as possible within their respective MLC fields, considering the discrete width of collimator leaves. The phantom, with the PTFE replaced by steel spheres, was placed on the treatment couch and imaged using stereoscopic x-ray beams. A 6 degree-of-freedom robotic couch applied translations and rotations to reproduce the CT position. A MV EPID rendered images of the spheres within their respective apertures, allowing identification of sphere and aperture centers. Any error upstream would manifest itself as inaccurate centering of a sphere. RESULTS: Eight beams with table angle 0 and two beams each with table angles 49.7, 89.8, 272.3, and 310.1 were selected. The maximum calculated distance between any sphere and the respective aperture center was 0.07 mm. The median difference measured from the MV images ranged from 0.1 mm to 1.4 mm with a median of 0.8 mm. CONCLUSIONS: The MTT is a practical end-to-end test for quality assurance of the entire positioning process in multitarget radiosurgery, from CT scanning to beam delivery.

SU-E-J-141: Assessment of the Magnitude and Impact of Trigger Delay in Respiratory Triggered Real-Time Imaging during Radiotherapy.

PURPOSE: To assess the trigger delay in respiratory triggered real-time imaging and its impact on image guided radiotherapy (IGRT) with Varian TrueBeam System. METHODS: A sinusoidal motion phantom with 2cm motion amplitude was used. The trigger delay was determined directly with video image, and indirectly by the distance between expected and actual triggering phantom positions. For the direct method, a fluorescent screen was placed on the phantom to visualize the x-ray. The motion of the screen was recorded at 60 frames/second. The number of frames between the time when the phantom reached expected triggering position and the time when the screen was illuminated by the x-ray was used to determine the trigger delay. In the indirect method, triggered kV x-ray images were acquired in real-time during 'treatment' with triggers set at 25% and 75% respiratory phases where the phantom moved at the maximum speed. 39-40 triggered images were acquired continuously in each series. The distance between the expected and actual triggering points, d, was measured on the images to determine the delay time t by d=Asin(wt), where w=2π/T, T=period and A=amplitude. Motion periods of 2s and 4s were used in the measurement. RESULTS: The trigger delay time determined with direct video imaging was 125ms (7.5 video frames). The average distance between the expected and actual triggering positions determined by the indirect method was 3.93±0.74mm for T=4s and 7.02±1.25mm for T=2s, yielding mean trigger delay times of 126±24ms and 120±22ms, respectively. Although the mean over-travel distance is significant at 25% and 75% phases, clinically, the target over-travel resulted from the trigger delay at the end of expiration (50% phase) is negligibly small(< 0.5mm). CONCLUSIONS: The trigger delay in respiration-triggered imaging is in the range of 120-126ms. This delay has negligible clinical effect on gated IGRT.

SU-E-T-433: Pear-Shaped Based Dose Optimization for HDR Intracavitary Brachytherapy for Cervical Cancer Patients with Small Uterus.

PURPOSE: Currently, CT has been widely used for HDR planning as MRI is not widely available for tumor imaging. Conventional pear-shaped isodose distribution may not be discarded completely because of possible microscopic diseases into parametrium/uterus. For patients with small uterus, organs at risk (OARs) can fall inside 100% conventional pear-shaped isodose-line. This study compares two pear-shaped based dose optimization methods for OARs sparing. METHODS: Seven cervical cancer patients with small uterus were evaluated using 2 methods. For Method A, with conventional dwell-time loading, point A lateral distance was reduced until all OARs' D2cc were within the dose limits. For Method B, a reference target volume was generated using conventional pear-shaped 100% isodose- surface. While isodose-line near the point A was adjusted for OARs sparing, isodose-line surrounding ovoids were optimized to match the reference target volume. For equivalent OAR sparing, 100% isodose-line width (lateral dimension) at 1 cm inferior to point A (-1 cm) and at across centers of ovoids (ovoid) were compared between the 2 methods. RESULTS: OARs fall inside conventional 100% isodose-line in all cases. Median position of hot spots was 0.2 cm (range -;1.2 to 2.9 cm) superior to point A. Using Method A, point A lateral distance was adjusted to 1.4-1.7 cm for OARs sparing. Median width of 100% isodose-line was 5.82 cm at ovoid level, and 4.50 cm at -1 cm level. At ovoid level, median width of 100% isodose-line was reduced by 9(8-13)% for Method A, and was unchanged for Method B. At -1 cm level, median width of 100% isodose-line was reduced by 19(2- 33)% for Method A, and 11(0-15)% for Method B. CONCLUSIONS: for patients with small uterus, OARs are often fall inside 100% pear-s haped isodose-line near point A level. OARs can be spared without dramatically compromise treatment volume coverage around cervix using Method B.

SU-E-T-447: Evaluation of the Anisotropic Analytical Algorithm (AAA) Heterogeneity Correction Dose Calculation in Flattened and Flattening- Filter-Free (FFF) Beams for High Energy X-Ray Beams Using the Radiological Physics Center (RPC) Lung Phantom.

PURPOSE: Compare the accuracy of AAA heterogeneity corrected dose calculation algorithm for high energy x-ray beams (>10 MV) for flattened and FFF beams using RPC anthropomorphic thorax phantom. METHODS: Six static beam SBRT treatment plans were created using the Varian Eclipse treatment planning system (TPS) AAA v.8.9.08 heterogeneity correction algorithm. Two flattened beam plans (6 MV and 18 MV) and four other plans (6 MV, 6 MV FFF, 10 MV FFF and 15 MV) were delivered using a Clinac 21EX and TrueBeam STx, respectively. Prescription dose/coverage, 6 Gy to 95% PTV, and constraints were the same for all plans. The phantom contained radiochromic films in the 3 major planes and TLDs in the heart, spine, and tumor. Point doses and 2D dose distributions were exported from the Eclipse TPS and compared with the measured doses. The gamma index analysis evaluation criteria of ±5% dose to agreement and 3 mm distance to agreement was used. RESULTS: TLD to TPS tumor point dose ratios were 0.971±0.006(6MV) and 0.957±0.002(6MV), 0.995±0.005(15MV), 1.114±0.006(18MV), and 0.957±0.003(6MV FFF), 0.974±0.011(10MV FFF) for the six plans. Using ±5%/3mm gamma analysis criteria, the average passing rates for all three films were 96.3% and 95.5%, 97.4%, 66.1%, 93.7%, and 96.3% for the 6 MV, 6 MV, 15 MV, 18 MV, 6 MV FFF, and 10 MV FFF plans, respectively. Dose profiles were also evaluated. CONCLUSIONS: The current RPC credentialing criteria are: RPC/Inst. tumor dose ratio of 0.97±0.05 and 85% of the pixels in each film plane must pass a ±5%/5mm gamma index analysis. These data demonstrate that the AAA heterogeneity correction dose calculation algorithm is accurate for photon energies in 6-15 MV range for flattened and FFF beams. Heterogeneity corrected dose calculations for photon energies >15 MV were not accurate. Work supported by grants CA10953 and CA81647 (NCI, DHHS).

MO-D-BRB-06: JUNIOR INVESTIGATOR WINNER - Fast and Accurate Patient Specific Collision Detection for Radiation Therapy.

PURPOSE: To develop a fast and generalizable method which can identify all possible hardware collisions specific to a given patient setup before treatment planning. METHODS: An anthropomorphic phantom placed in a typical breast setup using a wingboard was simulated on a CT scanner and the phantom body contour, table, and gantry geometry were made into polygon meshes using 3D modeling software. In the treatment room, a limited physical search of the collision positive zones was performed using the positioned phantom. A software tool that incorporated a generalized hierarchical bounding box (HBB) collision detection algorithm was developed and used to virtually map out the entire collision space by transforming the positions of the polygonal geometry over a given parameter range. RESULTS: The geometry containing 47K polygons was mapped over a space of 6480 states with an average transform/collision check of 5.5ms, for a total time of 35.6s on a 3.14GHz dual core computer with 4GB memory. The computed collision space, using receiver operating curve analysis had an accuracy of 96.35%, and a positive predictive value of 91.2%. CONCLUSIONS: This work demonstrates a framework that can provide a fast and accurate map of the collision free space specific to any patient setup. Differences in physical and simulated collision space is attributed to inaccuracies of the geometrical models used. Future work includes improving the efficiency of the algorithm, enhancing the geometrical models and increasing the dimensions of the search.