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At least 1,657 records · Page 92
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planning target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

Current understanding of interactions between nanoparticles and the immune system

The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Fitness Landscape-Guided Engineering of Locally Supercharged Virus-like Particles with Enhanced Cell Uptake Properties

Protein-based nanoparticles are useful models for the study of self-assembly and attractive candidates for drug delivery. Virus-like particles (VLPs) are especially promising platforms for expanding the repertoire of therapeutics that can be delivered effectively as they can deliver many copies of a molecule per particle for each delivery event. However, their use is often limited due to poor uptake of VLPs into mammalian cells. In this study, we use the fitness landscape of the bacteriophage MS2 VLP as a guide to engineer capsid variants with positively charged surface residues to enhance their uptake into mammalian cells. By combining mutations with positive fitness scores that were likely to produce assembled capsids, we identified two key double mutants with internalization efficiencies as much as 67-fold higher than that of wtMS2. Internalization of these variants with positively charged surface residues depends on interactions with cell surface sulfated proteoglycans, and yet, they are biophysically similar to wtMS2 with low cytotoxicity and an overall negative charge. Additionally, the best-performing engineered MS2 capsids can deliver a potent anticancer small-molecule therapeutic with efficacy levels similar to antibody-drug conjugates. Through this work, we were able to establish fitness landscape-based engineering as a successful method for designing VLPs with improved cell penetration. These findings suggest that VLPs with positive surface charge could be useful in improving the delivery of small-molecule- and nucleic acid-based therapeutics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Nicotinamide-Loaded Peptoid Nanotubes for Energy Regeneration in Acute Brain Injury

Acute brain injuries such as perinatal asphyxia, stroke, and traumatic brain injury result in ischemia, oxidative stress, excitotoxicity, and inflammation, leading to a depletion of ATP. Nicotinamide adenine dinucleotide (NAD+) is crucial for ATP regeneration and DNA repair during postinjury recovery. However, the therapeutic benefits of NAD+ and its precursors, such as nicotinamide (NAM), are limited by challenges in achieving effective cell-specific intracellular delivery. In this study, we use a nanopeptoid delivery strategy to replenish the cellular redox state and increase energy production in the acutely injured brain. By self-assembling peptoids into tubular structures, we created biocompatible NAM-conjugated peptoid nanotubes (NAM-PNTs) that vary in tubular length. NAM-PNTs demonstrated significant therapeutic benefits by enhancing cell viability and replenishing intracellular ATP levels within 24 h of treatment in oxygen–glucose-deprived (OGD) BV-2 cells. In organotypic brain slices, NAM-PNT treatment promoted glial proliferation, reduced proinflammatory cytokines, and increased anti-inflammatory cytokines after OGD, an ex vivo model of hypoxia-ischemia. The effect of NAM-PNTs is associated with their uptake into microglia via fluid-phase phagocytosis and caveolae-mediated endocytosis. A single systemic dose of NAM-PNTs localized in microglia in the injured hemisphere and reduced brain tissue loss and improved neuropathology after hypoxia-ischemia in term-equivalent rats. These findings highlight the therapeutic potential of NAM-PNTs for cell-specific targeted delivery and energy restoration in the acutely injured neonatal brain. In the neonatal brain injury field, this work demonstrates the development of an innovative nanoparticle platform from first-principles design and synthesis to in vitro screening and then demonstration of efficacy in vivo .

ATP↗
DOE OSTI2024

Engineering self-deliverable ribonucleoproteins for genome editing in the brain

The delivery of CRISPR ribonucleoproteins (RNPs) for genome editing in vitro and in vivo has important advantages over other delivery methods, including reduced off-target and immunogenic effects. However, effective delivery of RNPs remains challenging in certain cell types due to low efficiency and cell toxicity. To address these issues, we engineer self-deliverable RNPs that can promote efficient cellular uptake and carry out robust genome editing without the need for helper materials or biomolecules. Screening of cell-penetrating peptides (CPPs) fused to CRISPR-Cas9 protein identifies potent constructs capable of efficient genome editing of neural progenitor cells. Further engineering of these fusion proteins establishes a C-terminal Cas9 fusion with three copies of A22p, a peptide derived from human semaphorin-3a, that exhibits substantially improved editing efficacy compared to other constructs. We find that self-deliverable Cas9 RNPs generate robust genome edits in clinically relevant genes when injected directly into the mouse striatum. Overall, self-deliverable Cas9 proteins provide a facile and effective platform for genome editing in vitro and in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabled sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.

36 MATERIALS SCIENCE↗
DOE OSTI2023

A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography

Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip' for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip , 21 , 4831–4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70 Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

SU-E-T-144: Effective Analysis of VMAT QA Generated Trajectory Log Files for Medical Accelerator Predictive Maintenance

Purpose: To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files. Methods: Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry and each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy. Results: All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC. Conclusion: SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2015

SU-E-T-564: Multi-Helix Rotating Shield Brachytherapy for Cervical Cancer

Purpose: To present a novel and practical brachytherapy technique, called multi-helix rotating shield brachytherapy (H-RSBT), for the precise positioning of a partial shield in a curved applicator. H-RSBT enables RSBT delivery using only translational motion of the radiation source/shield combination. H-RSBT overcomes the challenges associated with previously proposed RSBT approaches based on a serial (S-RSBT) step-and-shoot delivery technique, which required independent translational and rotational motion. Methods: A Fletcher-type applicator, compatible with the combination of a Xoft Axxent™ electronic brachytherapy source and a 0.5 mm thick tungsten shield, is proposed. The wall of the applicator contains six evenly-spaced helical keyways that rigidly define the emission direction of the shield as a function of depth. The shield contains three protruding keys and is attached to the source such that it rotates freely. S-RSBT and H-RSBT treatment plans with 180° and 45° azimuthal emission angles were generated for five cervical cancer patients representative of a wide range of high-risk clinical target volume (HR-CTV) shapes and applicator positions. The number of beamlets used in the treatment planning process was nearly constant for S-RSBT and H-RSBT by using dwell positions separated by 5 and 1.7 mm, respectively, and emission directions separated by 22.5° and 60°, respectively. For all the treatment plans the EQD2 of the HR-CTV was escalated until the EQD{sub 2cc} tolerance of either the bladder, rectum, or sigmoid colon was reached. Results: Treatment times for H-RSBT tended to be shorter than for S-RSBT, with changes of −38.47% to 1.12% with an average of −8.34%. The HR-CTV D{sub 90} changed by −8.81% to 2.08% with an average of −2.46%. Conclusion: H-RSBT is a mechanically feasible technique in the curved applicators needed for cervical cancer brachytherapy. S-RSBT and H-RSBT dose distributions were clinically equivalent for all patients considered, with the H-RSBT deliveries tending to be faster. Ryan Flynn has ownership interest in pxAlpha, LLC, which is a startup company developing a rotating shield brachytherapy system.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Technical Note: Validation and implementation of a wireless transponder tracking system for gated stereotactic ablative radiotherapy of the liver

Purpose: Tracking soft-tissue targets has recently been cleared as a new application of Calypso, an electromagnetic wireless transponder tracking system, allowing for gated treatment of the liver based on the motion of the target volume itself. The purpose of this study is to describe the details of validating the Calypso system for wireless transponder tracking of the liver and to present the clinical workflow for using it to deliver gated stereotactic ablative radiotherapy (SABR). Methods: A commercial 3D diode array motion system was used to evaluate the dynamic tracking accuracy of Calypso when tracking continuous large amplitude motion. It was then used to perform end-to-end tests to evaluate the dosimetric accuracy of gated beam delivery for liver SABR. In addition, gating limits were investigated to determine how large the gating window can be while still maintaining dosimetric accuracy. The gating latency of the Calypso system was also measured using a customized motion phantom. Results: The average absolute difference between the measured and expected positional offset was 0.3 mm. The 2%/2 mm gamma pass rates for the gated treatment delivery were greater than 97%. When increasing the gating limits beyond the known extent of planned motion, the gamma pass rates decreased as expected. The 2%/2 mm gamma pass rate for a 1, 2, and 3 mm increase in gating limits was measured to be 97.8%, 82.9%, and 61.4%, respectively. The average gating latency was measured to be 63.8 ms for beam-hold and 195.8 ms for beam-on. Four liver patients with 17 total fractions have been successfully treated at our institution. Conclusions: Wireless transponder tracking was validated as a dosimetrically accurate way to provide gated SABR of the liver. The dynamic tracking accuracy of the Calypso system met manufacturer’s specification, even for continuous large amplitude motion that can be encountered when tracking liver tumors close to the diaphragm. The measured beam-hold gating latency was appropriate for targets that will traverse the gating limit each respiratory cycle causing the beam to be interrupted constantly throughout treatment delivery.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-149: Development of the Monte Carlo Simulation Platform Using Geant4 for Designing Heavy Ion Therapy Beam Nozzle

Purpose: The significant issue of particle therapy such as proton and carbon ion was a accurate dose delivery from beam line to patient. For designing the complex delivery system, Monte Carlo simulation can be used for the simulation of various physical interaction in scatters and filters. In this report, we present the development of Monte Carlo simulation platform to help design the prototype of particle therapy nozzle and performed the Monte Carlo simulation using Geant4. Also we show the prototype design of particle therapy beam nozzle for Korea Heavy Ion Medical Accelerator (KHIMA) project in Korea Institute of Radiological and Medical Science(KIRAMS) at Republic of Korea. Methods: We developed a simulation platform for particle therapy beam nozzle using Geant4. In this platform, the prototype nozzle design of Scanning system for carbon was simply designed. For comparison with theoretic beam optics, the beam profile on lateral distribution at isocenter is compared with Mont Carlo simulation result. From the result of this analysis, we can expected the beam spot property of KHIMA system and implement the spot size optimization for our spot scanning system. Results: For characteristics study of scanning system, various combination of the spot size from accerlator with ridge filter and beam monitor was tested as simple design for KHIMA dose delivery system. Conclusion: In this report, we presented the part of simulation platform and the characteristics study. This study is now on-going in order to develop the simulation platform including the beam nozzle and the dose verification tool with treatment planning system. This will be presented as soon as it is become available.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-168: Development and Implementation of An Anthropomorphic Head & Neck Phantom for the Assessment of Proton Therapy Treatment Procedures

Purpose: To design a Head and Neck (H&N) anthropomorphic QA phantom that the Imaging and Radiation Oncology Core Houston (IROC-H) can use to verify the quality of intensity modulated proton therapy (IMPT) H&N treatments for institutions participating in NCI clinical trials. Methods: The phantom was created to serve as a remote auditing tool for IROC-H to evaluate an institution’s IMPT planning and delivery abilities. The design was based on the composition, size, and geometry of a generalized oropharyngeal tumor and contains critical structures (parotids and spinal cord). Radiochromic film in the axial and sagittal planes and thermoluminescent dosimeters (TLD)-100 capsules were embedded in the phantom and used to perform the dose delivery evaluation. A CT simulation was used to create a passive scatter and a spot scanning treatment plan with typical clinical constraints for H&N cancer. The IMPT plan was approved by a radiation oncologist and the phantom was irradiated multiple times. The measured dose distribution using a 7%/4mm gamma analysis (85% of pixels passing) and point doses were compared with the treatment planning system calculations. Results: The designed phantom could not achieve the target dose prescription and organ at risk dose constraints with the passive scatter treatment plan. The target prescription dose could be met but not the parotid dose constraint. The average TLD point dose ratio in the target was 0.975, well within the 5% acceptance criterion. The dose distribution analysis using various acceptance criteria, 5%/4mm, 5%/3mm, 7%/4mm and 7%/5mm, had average pixel passing rates of 85.9%, 81.8%, 89.6% and 91.6%, and respectively. Conclusion: An anthropomorphic IMPT H&N phantom was designed that can assess the dose delivery of proton sites wishing to participate in clinical trials using a 5% TLD dose and 7%/4mm gamma analysis acceptance criteria.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-227: A Comprehensive Patient Specific, Structure Specific, Pre-Treatment 3D QA Protocol for IMRT, SBRT and VMAT - Clinical Experience

Purpose: To present a 3D QA method and clinical results for 550 patients. Methods: Five hundred and fifty patient treatment deliveries (400 IMRT, 75 SBRT and 75 VMAT) from various treatment sites, planned on Raystation treatment planning system (TPS), were measured on three beam-matched Elekta linear accelerators using IBA’s COMPASS system. The difference between TPS computed and delivered dose was evaluated in 3D by applying three statistical parameters to each structure of interest: absolute average dose difference (AADD, 6% allowed difference), absolute dose difference greater than 6% (ADD6, 4% structure volume allowed to fail) and 3D gamma test (3%/3mm DTA, 4% structure volume allowed to fail). If the allowed value was not met for a given structure, manual review was performed. The review consisted of overlaying dose difference or gamma results with the patient CT, scrolling through the slices. For QA to pass, areas of high dose difference or gamma must be small and not on consecutive slices. For AADD to manually pass QA, the average dose difference in cGy must be less than 50cGy. The QA protocol also includes DVH analysis based on QUANTEC and TG-101 recommended dose constraints. Results: Figures 1–3 show the results for the three parameters per treatment modality. Manual review was performed on 67 deliveries (27 IMRT, 22 SBRT and 18 VMAT), for which all passed QA. Results show that statistical parameter AADD may be overly sensitive for structures receiving low dose, especially for the SBRT deliveries (Fig.1). The TPS computed and measured DVH values were in excellent agreement and with minimum difference. Conclusion: Applying DVH analysis and different statistical parameters to any structure of interest, as part of the 3D QA protocol, provides a comprehensive treatment plan evaluation. Author G. Gueorguiev discloses receiving travel and research funding from IBA for unrelated to this project work. Author B. Crawford discloses receiving travel funding from IBA for unrelated to this project work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-266: Dynalogs Based Evaluation of Different Dose Rate IMRT Using DVH and Gamma Index

Purpose: This work investigates the impact of low and high dose rate on IMRT through Dynalogs by evaluating Gamma Index and Dose Volume Histogram. Methods: The Eclipse™ treatment planning software was used to generate plans on prostate and head and neck sites. A range of dose rates 300 MU/min and 600 MU/min were applied to each plan in order to investigate their effect on the beam ON time, efficiency and accuracy. Each plan had distinct monitor units per fraction, delivery time, mean dose rate and leaf speed. The DVH data was used in the assessment of the conformity and plan quality.The treatments were delivered on Varian™ Clinac 2100C accelerator equipped with 120 leaf millennium MLC. Dynalogs of each plan were analyzed by MATLAB™ program. Fluence measurements were performed using the Sun Nuclear™ 2D diode array and results were assessed, based on Gamma analysis of dose fluence maps, beam delivery statistics and Dynalogs data. Results: Minor differences found by adjusted R-squared analysis of DVH’s for all the plans with different dose rates. It has been also found that more and larger fields have greater time reduction at high dose rate and there was a sharp decrease in number of control points observed in dynalog files by switching dose rate from 300 MU/min to 600 MU/min. Gamma Analysis of all plans passes the confidence limit of ≥95% with greater number of passing points in 300 MU/min dose rate plans. Conclusion: The dynalog files are compatible tool for software based IMRT QA. It can work perfectly parallel to measurement based QA setup and stand-by procedure for pre and post delivery of treatment plan.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generated for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and investigate other cross-platform treatment delivery options.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-506: Development and Commissioning of the Effective and Efficient Grid Therapy Using High Dose Rate Flattening Filter Free Beam and Multileaf Collimator

Purpose: Treating bulky tumors with grid therapy (GT) has demonstrated high response rates. Long delivery time (∼15min), with consequent increased risk of intrafraction motion, is a major disadvantage of conventional MLC-based GT (MLC-GT). The goal of this study was to develop and commission a MLC-GT technique with similar dosimetric characteristics, but more efficient delivery. Methods: Grid plan was designed with 10X-FFF (2400MU/min) beam and MLC in a commercial treatment planning system (TPS). Grid size was 1cm by 1cm and grid-to-grid distance was 2cm. Field-in-field technique was used to flatten the dose profile at depth of 10cm. Prescription was 15Gy at 1.5cm depth. Doses were verified at depths of 1.5cm, 5cm and 10cm. Point dose was measured with a plastic scintillator detector (PSD) while the planar dose was measured with calibrated Gafchromic EBT3 films in a 20cm think, 30cmx30cm solid water phantom. The measured doses were compared to the doses calculated in the treatment planning system. Percent depth dose (PDD) within the grid was also measured using EBT3 film. Five clinical cases were planned to compare beam-on time. Results: The valley-to-peak dose ratio at the 3 depths was approximately 10–15%, which is very similar to published result. The average point dose difference between the PSD measurements and TPS calculation is 2.1±0.6%. Film dosimetry revealed good agreement between the delivered and calculated dose. The average gamma passing rates at the 3 depths were 95% (3%, 1mm). The average percent difference between the measured PDD and calculated PDD was 2.1% within the depth of 20cm. The phantom plan delivery time was 3.6 min. Average beam-on time was reduced by 66.1±5.6% for the 5 clinical cases. Conclusion: An effective and efficient GT technique was developed and commissioned for the treatment of bulky tumors using FFF beam combined with MLC and automation. The Department of Radiation Oncology at Henry Ford Health System receives research support from Varian Medical Systems and Philips Health Care.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-632: On the Use of Intensity Modulated Arc Therapy for Thoracic Vertebral Metastases SBRT Treatment

Purpose: To retrospectively evaluate quality, efficiency and delivery accuracy of intensity modulated arc therapy (IMAT) plans for thoracic-vertebral metastases using stereotactic body radiotherapy (SBRT). Methods: After obtaining approval of RPC-benchmark plan, seven previously treated thoracic-vertebral metastases patients with non-coplanar hybrid arcs(NC-HA)using 1–2 3D-dynamic conformal partial-arcs plus 7–9 IMRT-beams were re-optimized with IMAT using 3 full co-planar arcs. Tumors were located between T2–T7. T1/T2-weighted MRI images were co-registered with planning-CT. PTVs were between 24.3–240.1cc(median=48.1cc). Prescription was 30Gy in 5 fractions with 6-MV beams at Novalis-TX consisting of HD-MLC.Plans were compared for target coverage:conformality index(CI),homogeneity index(HI),PTVD90. Organs-at-risks(OARs)was evaluated for spinal cord(Dmax, D0.35cc, and D1.2cc), esophagus(Dmax and D5cc),heart(Dmax, D15cc)and lung(V5 and V10). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance(QA) plan. Beam-on time was recorded and a gamma index was used to compare agreement between planned and measured doses. Results: SBRT IMAT plans resulted in superior CI(1.02 vs. 1.36, p=0.05) and HI (0.14 vs. 0.27, p=0.01). PTVD90 was improved but statistically insignificant (31.0 vs. 30.4Gy, p=0.38). IMAT resulted in statistically significant improvements in OARs sparing: esophagus max(22.5 vs. 27.0Gy, p=0.03), esophagus 5cc (17.6 vs. 21.5Gy, p=0.02) and heart max(13.1 vs. 15.8Gy, p=0.03). Spinal cord,lung V5 and V10 were lower but statistically insignificant. Average total MU and beam-on time were 2598±354 vs. 3542±495 and 4.7±0.6 min vs. 7.1±1.0min for IMAT vs. NC-HA (without accounting for couch kicks time for NC-HA). IMAT plans demonstrated an accurate dose delivery of 95.5±1.0% for clinical gamma passing-rate of 2%/2mm criteria on MapCHECK, that was comparable to NC-HA plans. Conclusion: IMAT plans provided highly conformal and homogeneous dose distributions to target and reduced OARs doses compared to NC-HA. Total MU was reduced by a factor of 1.4 and subsequently decreased treatment times significantly - potentially minimizing intra-fraction motion error and owing to patient comfort. SBRT using IMAT planning for single fraction thoracic-vertebrae metastases will be investigated.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-634: Feasibility Study of Respiratory Gated RapidArc SBRT Using a 6MV FFF Photon Beam

Purpose: To conduct a feasibility study on retrospective respiratory gating and marker tracking for lung stereotactic body radiotherapy (SBRT) with a gated RapidArc delivery using a 6MV flattened filter free photon mode. Methods: A CIRS dynamic thorax phantom Model 008A with different inserts was used for treatment planning and respiratory gating. 4D CT had a free breathing simulation followed by a respiration gated, ten phased CT using a Philips Brilliance CT with a Varian RPM respiratory gating system. The internal target volume was created from the ten phase gated CT images, followed by exporting to a Varian Eclipse TPS v11 for treatment planning on the free breath images. Both MIP and AIP were also generated for comparison of planning and target motion tracking. The planned dose was delivered with a 6MV FFF photon beam from a Varian TrueBeam accelerator. Gated target motion was also verified by tracking the implanted makers during delivery using continuous kV imaging in addition to CBCT, kV and MV localization and verification. Results: Gating was studied in three situations of lower, normal, and faster breathing at a respiratory cycle of 5, 15 and 25 breaths per minute, respectively. 4D treatment planning was performed at a normal breathing of 15 breaths per minute. The gated patterns obtained using the TrueBeam IR camera were compared with the planned ones while gating operation was added prior to delivery . Gating was realized only when the measured respiratory patterns matched to the planned ones. The gated target motion was verified within the tolerance by kV and MV imaging. Either free breathing CT or averaged CT images were studied to be good for image guidance to align the target. Conclusion: Gated RapidArc SBRT delivered with a 6MV FFF photon beam is realized using a dynamic lung phantom.

60 APPLIED LIFE SCIENCES↗