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PURPOSE: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. METHODS AND MATERIALS: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45–75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy. RESULTS: Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45–66 Gy) delivered in 30 fractions (range, 15–33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%–12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. CONCLUSIONS: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.

Objective: Current ventilation and perfusion dose–response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose–responses among lung cancer patients treated with radiotherapy. Methods: 20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0–60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans. Results: 25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20–30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes. Conclusion: Our data showed that ventilation dose–response can differ from perfusion dose–response for 20–30% of patients. Therefore, when performing thoracic dose–response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes. Advances in knowledge: The significance of this study can be highlighted by the differences between the intrapatient dose–response assessments of this analysis compared to existing population-based dose–response analyses. Elucidating intrapatient ventilation and perfusion dose–response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.

Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy.Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEVFifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEVThe current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation- coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.Methods and materialsThis study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.ResultsNinety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of

Stereotactic body radiation therapy (SBRT) has emerged as an effective, noninvasive treatment option for primary liver cancer and metastatic disease occurring in the liver. Although SBRT can be highly effective for establishing local control in hepatic malignancies, a tradeoff exists between tumor control and normal tissue complications. The objective of the present study was to review the normal tissue dose-volume effects for SBRT-induced liver and gastrointestinal toxicities and derive normal tissue complication probability models.

Purpose To identify causes of error, and present the concept of an automated technique that improves efficiency and helps to reduce transcription and manual data entry errors in the treatment planning of total body irradiation (TBI). Methods Analysis of incidents submitted to incident learning system (ILS) was performed to identify potential avenues for improvement by implementation of automation of the manual treatment planning process for total body irradiation (TBI). Following this analysis, it became obvious that while the individual components of the TBI treatment planning process were well implemented, the manual ‘bridging’ of the components (transcribing data, manual data entry etc.) were leading to high potential for error. A C#‐based plug‐in treatment planning script was developed to remove the manual parts of the treatment planning workflow that were contributing to increased risk. Results Here we present an example of the implementation of “Glue” programming, combining treatment planning C# scripts with existing spreadsheet calculation worksheets. Prior to the implementation of automation, 35 incident reports related to the TBI treatment process were submitted to the ILS over a 6‐year period, with an average of 1.4 ± 1.7 reports submitted per quarter. While no incidents reached patients, reports ranged from minor documentation issues to potential for mistreatment if not caught before delivery. Since the implementation of automated treatment planning and documentation, treatment planning time per patient, including documentation, has been reduced; from an average of 45 min pre‐automation to

Purpose Studies have noted a link between radiation dose to the heart and overall survival (OS) for patients with lung cancer treated with chemoradiation. The purpose of this study was to characterize pre- to posttreatment cardiac metabolic changes using fluorodeoxyglucose/positron emission tomography (FDG-PET) images and to evaluate whether changes in cardiac metabolism predict for OS. Methods and Materials Thirty-nine patients enrolled in a functional avoidance prospective study who had undergone pre- and postchemoradiation FDG-PET imaging were evaluated. For each patient, the pretreatment and posttreatment PET/CTs were rigidly registered to the planning CT, dose, and structure set. PET-based metabolic dose-response was assessed by comparing pretreatment to posttreatment mean standardized uptake values (SUVmean) in the heart as a function of dose-bin. OS analysis was performed by comparing SUVmean changes for patients who were alive or had died at last follow-up and by using a multivariate model to assess whether pre- to posttreatment SUVmean changes were a predictor of OS. Results The dose-response curve revealed increasing changes in SUV as a function of cardiac dose with an average SUVmean increase of 1.7% per 10 Gy. Patients were followed for a median of 437 days (range, 201-1131 days). SUVmean change was significantly predictive of OS on multivariate analysis with a hazard ratio of 0.541 (95% confidence intervals, 0.312-0.937). Patients alive at follow-up had an average increase of 17.2% in cardiac SUVmean while patients that died had an average decrease in SUVmean decrease of 13.5% (P = .048). Conclusions Our data demonstrated that posttreatment SUV changes in the heart were significant indicators of dose-response and predictors of OS. The present work is hypothesis generating and must be validated in an independent cohort. If validated, our data show the potential for cardiac metabolic changes to be an early predictor for clinical outcomes.

Three-dimensional in-vivo dose verification is one of the standing challenges in radiation therapy. X-ray-induced acoustic tomography has recently been proposed as an imaging method for use in in-vivo dosimetry. The aim of this study was to investigate the accuracy of reconstructing three-dimensional (3D) absolute dose using x-ray-induced acoustic tomography. We performed this investigation using two different tomographic dose reconstruction techniques.Two examples of 3D dose reconstruction techniques for x-ray acoustic imaging are investigated. Dose distributions are calculated for varying field sizes using a clinical treatment planning system. The induced acoustic pressure waves which are generated by the increase in temperature due to the absorption of pulsed MV x-rays are simulated using an advanced numerical modeling package for acoustic wave propagation in the time domain. Two imaging techniques, back projection and iterative time reversal, are used to reconstruct the 3D dose distribution in a water phantom with open fields. Image analysis is performed and reconstructed depth dose curves from x-ray acoustic imaging are compared to the depth dose curves calculated from the treatment planning system. Calculated field sizes from the reconstructed dose profiles by back projection and time reversal are compared to the planned field size to determine their accuracy. The iterative time reversal imaging technique is also used to reconstruct dose in an example clinical dose distribution. Image analysis of this clinical test case is performed using the gamma passing rate. In addition, gamma passing rates are used to validate the stopping criteria in the iterative time reversal method.Water phantom simulations showed that back projection does not adequately reconstruct the shape and intensity of the depth dose. When compared to the depth of maximum dose calculated by a treatment planning system, the maximum dose depth by back projection is shifted deeper by 55 and 75 mm for 4 × 4 cm and 10 × 10 cm field sizes, respectively. The reconstructed depth dose by iterative time reversal accurately agrees with the planned depth dose for a 4 × 4 cm field size and is shifted deeper by 12 mm for the 10 × 10 cm field size. When reconstructing field sizes, the back projection method leads to 18% and 35% larger sizes for the 4 × 4 cm and 10 × 10 cm fields, respectively, whereas the iterative time reversal method reconstructs both field sizes with 2% error. For the clinical dose distribution, we were able to reconstruct the dose delivered by a 1 degree sub-arc with a good accuracy. The reconstructed and planned doses were compared using gamma analysis, with 96% gamma passing rate at 3%/2 mm.Our results show that the 3D x-ray acoustic reconstructed dose by iterative time reversal is considerably more accurate than the dose reconstructed by back projection. Iterative time reversal imaging has a potential for use in 3D absolute dosimetry.

Objective. The concept of using kilovoltage (kV) and megavoltage (MV) beams concurrently has potential applications in cone beam computed tomography (CBCT) guided radiation therapy, such as single breath hold scans, metal artifact reduction, and simultaneous imaging during MV treatment delivery. However, MV cross-scatter generated during MV beam delivery degrades CBCT image quality. To address this, a 2D antiscatter grid and a cross-scatter correction method were investigated in the context of high dose MV treatment delivery. Approach. A 3D printed, tungsten 2D antiscatter grid prototype was utilized in kV CBCT scans to reduce MV cross-scatter fluence during concurrent MV beam delivery. Remaining cross-scatter in projections was corrected by using the 2D grid itself as a cross-scatter intensity sampling device, referred to as grid-based scatter sampling (GSS). To test this approach, kV CBCT acquisitions were performed while delivering 6 and 10 MV beams, mimicking high dose rate treatment delivery scenarios. kV and MV beam deliveries were not synchronized to eliminate MV beam delivery interruption. MV cross-scatter suppression performance of the proposed approach was evaluated in projections and CBCT images of phantoms. Main results. 2D grid reduced the intensity of MV cross-scatter in kV projections by a factor of 3 on the average, when compared to conventional antiscatter grid. Remaining cross scatter as measured by the GSS method was within 7% of measured reference intensity values, and subsequently corrected. CBCT image quality was improved substantially during concurrent kV–MV beam delivery. Median Hounsfield Unit (HU) inaccuracy was up to 182 HU without our methods, and it was reduced to a median 6.5 HU with our 2D grid and scatter correction approach. Our methods provided a factor of 2–6 improvement in contrast-to-noise ratio. Significance. This investigation demonstrates the utility of 2D antiscatter grids and grid-based scatter sampling in suppressing MV cross-scatter. Our approach successfully minimized the effects of MV cross-scatter in concurrent kV CBCT imaging and high dose MV treatment delivery scenarios. Hence, robust MV cross-scatter suppression is potentially feasible without MV beam delivery interruption or compromising kV image acquisition rate.

Purpose The pulse line ion accelerator (PLIA) is a low-cost accelerator concept originally designed to accelerate heavy ions. Our group has been investigating the use of PLIA to accelerate light ions and believe a multi-stage PLIA could be useful for short half-life PET isotope production. The goal of this work was to develop a single prototype fast PLIA structure and demonstrate electromagnetic wave propagation using a high-voltage pulser. Materials and methods A 1.6 m fast PLIA structure (wave speed > 107 m/s) was constructed along with a high-voltage, sinusoidal pulse generator. The latter uses capacitive voltage doubling and spark gap switching. A step-up transformer couples voltage from the pulser to the PLIA coil. Voltage measurements on the coil were made in air using a high-voltage resistive probe, while capacitive probes placed along the length of the PLIA were used to measure wave propagation with the PLIA structure filled with transformer oil. Results Voltage measurements acquired on the primary and secondary coils of the transformer coupler in air demonstrated a peak-to-peak voltage step-up of 4.2 relative to the pulser DC charging voltage. The maximum voltage time-rate-of-change on the PLIA coil was 0.76 × 1013 V/s. Capacitive probe measurements indicated voltage oscillations on the PLIA coil with half-period equal to 43 ± 0.9 ns and wave speed (with oil) of 1.2 × 107 m/s. Average and peak accelerating gradients were conservatively estimated to be 0.44 and 0.60 MV/m, respectively, with a charging voltage of 55 kV. Wave propagation was demonstrated at these gradients without flashover at a vacuum pressure of 9 × 10-6 Torr. Submerging the pulser in oil would allow for charging voltages up to 150 kV and produce accelerating gradients >1.2 MV/m. Conclusions Use of a multi-stage, fast PLIA for light ion acceleration could provide a low-cost complement to cyclotrons for the production of short half-life isotopes used for PET imaging, including carbon-11, nitrogen-13, oxygen-15, and fluorine-18.

Tumor motion plays a key role in the safe delivery of Stereotactic Body Radiotherapy (SBRT) for pancreatic cancer. The purpose of this study was to use tumor motion data measured in patients to establish limits on motion magnitude for safe delivery of pancreatic SBRT. Using 91 sets of pancreatic tumor motion data measured in patients, we calculated motion-convolved dose for 25 pancreatic cancer patients, and established the maximum amount of motion allowable while satisfying error thresholds on key dose metrics. In our patient cohort, the mean [min-max] allowable motion for 33/40/50 Gy to the PTV was 11.9 [6.3-22.4], 10.4 [5.2-19.1] and 9.0 [4.2-16.0] mm, respectively. Maximum allowable motion decreased as dose was escalated, and was smaller in patients with larger tumors. The effects of motion on pancreatic SBRT are highly variable between patients and there is potential to allow more motion in certain patients, even in dose-escalated scenarios. In our dataset, a conservative limit of 6.3 mm would ensure safe treatment of all patients treated to 33 Gy in 5 fractions., 9 pages, 5 figures, supplement included. Submitted to Practical Radiation Oncology

Purpose Two-dimensional antiscatter grids (2DASG) for cone beam computed tomography (CBCT) is a new area of research to reduce scatter intensity, and consequently improve CBCT image quality. One of the challenges in implementation of 2DASGs is their septa shadows that are impinged on the projections. If these artifacts are not corrected, they may lead to ring artifacts in CBCT images. In this work, we present a novel method to suppress ring artifacts in FPD-based CBCT images. Methods Briefly, our method first detects the locations of 2DASG's septa shadows in projections and then, reduces projection pixel values in septa shadows iteratively until a residual-based convergence criterion is met. To suppress the 2DASG's septa shadows, we developed a total variation minimization (TVM) formulation, referred to as adaptive-diffusive total variation minimization (adTVM), where the diffusivity regularization parameter was adaptively adjusted during each iteration based on the magnitude of the local pixel gradients. To test our method, we have acquired CBCT scans of phantoms using three 2DASG prototypes with different grid geometries. Projections were acquired with a linac mounted CBCT system, operated in offset detector geometry. These projections were then corrected in the following steps: first, projections were corrected using a gantry angle-specific gain correction map; next, projections were corrected by applying our adTVM method. CBCT images were reconstructed using FDK filtered backprojection algorithm. To evaluate adTVM's performance, pixel value statistics and contrast-to-noise ratio (CNR) were compared in CBCT images corrected with and without our adTVM method. Results Without our adTVM method, all three 2DASG prototypes introduced ring artifacts with varying intensities in CBCT images. With our method, significant reduction in ring artifacts was observed in all test cases. Standard deviation of CT numbers was reduced by 7-74% in uniform density phantom CBCT images, CNR was increased by 8-67%, and CT number accuracy of contrast objects embedded in the phantom was preserved. Conclusion We propose a new method to suppress ring artifacts caused by the 2DASG's septa shadows in CBCT images. Our initial investigations indicated that adTVM method could substantially reduce such ring artifacts while preserving CT number accuracy and maintaining good spatial resolution. Therefore, our method may potentially play an important role in enabling the implementation of 2DASGs in flat panel detector based CBCT systems.

Independent verification of the dose per monitor unit (MU) to deliver the prescribed dose to a patient has been a mainstay of radiation oncology quality assurance. We discuss the role of secondary dose/MU calculation programs as part of a comprehensive Quality Assurance (QA) program. This report provides guidelines on calculation-based dose/MU verification for intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) provided by various modalities. We provide a review of various algorithms for "independent/second check" of monitor unit calculations for IMRT/VMAT. The report makes recommendations on the clinical implementation of secondary dose/MU calculation programs; on commissioning and acceptance of various commercially available secondary dose/MU calculation programs; on benchmark QA and periodic quality assurance; and on clinically reasonable action levels for agreement of secondary dose/MU calculation programs.

PURPOSE We have been investigating two-dimensional (2D) antiscatter grids (2D ASGs) to reduce scatter fluence and improve image quality in cone beam computed tomography (CBCT). In this work, two different aspects of 2D ASGs, their scatter rejection and correction capability, were investigated in CBCT experiments. To correct residual scatter transmitted through the 2D ASG, it was used as a scatter measurement device with a novel method: grid-based scatter sampling. METHODS Three focused 2D ASG prototypes with grid ratios of 8, 12, and 16 were developed for linac-mounted offset detector CBCT geometry. In the first phase, 2D ASGs were used as a scatter rejection device, and the effect of grid ratio on CT number accuracy and contrast-to-noise ratio (CNR) evaluated in CBCT images. In the second phase, a grid-based scatter sampling method which exploits the signal modulation characteristics of the 2D ASG's septal shadows to measure and correct residual scatter transmitted through the grid was implemented. To evaluate CT number accuracy, the percent change in CT numbers was measured by changing the phantom from head to pelvis size and configuration. RESULTS When 2D ASG was used as a scatter rejection device, CT number accuracy increased and the CT number variation due to change in phantom dimensions was reduced from 23% to 2-6%. A grid ratio of 16 yielded the lowest CT number variation. All three 2D ASGs yielded improvement in CNR, up to a factor of two in pelvis-sized phantoms. When 2D ASG prototypes were used for both scatter rejection and correction, CT number variations were reduced further, to 1.3-2.6%. In comparisons with a clinical CBCT system and a high-performance radiographic ASG, 2D ASG provided higher CT number accuracy under the same imaging conditions. CONCLUSIONS When 2D ASG is used solely as a scatter rejection device, substantial improvement in CT number accuracy can be achieved by increasing the grid ratio. Two-dimensional ASGs also provided significant CNR improvement even at lower grid ratios. Two-dimensional ASGs used in conjunction with the grid-based scatter sampling method provided further improvement in CT number accuracy, irrespective of the grid ratio, while preserving 2D ASGs' capacity to improve CNR. The combined effect of scatter rejection and residual scatter correction by 2D ASG may accelerate implementation of new techniques in CBCT that require high quantitative accuracy, such as radiotherapy dose calculation and dual energy CBCT.

Purpose Real-time visualization of target motion using fiducial markers during radiation therapy treatment will allow for more accurate dose delivery. The purpose of this study was to optimize techniques for online fiducial marker tracking by detecting the scattered treatment beam through coded aperture imaging (CAI). Coded aperture imaging is a novel imaging technique that can allow target tracking in real time during treatment, and do so without adding any additional radiation dose, by making use of the scattered treatment beam radiation. Methods Radiotherapy beams of various energies, incident on phantoms containing gold fiducial markers were modeled using MCNP6.2 Monte Carlo transport code. Orthogonal scatter radiographs were collected through a CAI geometry. After decoding the simulated radiograph data, the centroid location and FWHM/SNR of the fiducial signals were analyzed. The effects of properties related to the CA (rank, pattern, and physical dimensions), detector (dimensions and pixel count), position (CA and phantom), and the incident beam (spectrum and direction) were investigated. These variables were evaluated by quantifying the positional accuracy, resolution, and SNR of the fiducials' signal. The effects of phantom scatter and decoding artifacts were reduced via Fourier filtering to avoid treatment interruption and physical interaction with the coded mask. Results The method was able to accurately localize the markers to within 1 pixel of a simulated radiograph. A 10 × 10 × 2 cm tungsten mask was chosen to attenuate >99 % of incident scatter through opaque elements, while minimizing collimation artifacts which arise from vignetting of the coded radiograph. Clear separation of centroids from fiducial signals with 2.5 mm separation was maintained, and initial optimization of parameters has produced an aperture which decodes the location of multiple fiducial markers inside a human phantom properly with a high SNR in the final radiograph image. Conclusion Current results show a proof of concept for a novel real-time imaging method. Coded aperture imaging is a promising technique for extracting the fiducial scatter signal from a broader Compton-scatter background. These results can be used to further optimize the CAI parameter space and guide fabrication and testing of a clinical device.

Purpose Positron emission tomography (PET) imaging remains limited due to the cost associated with on-site production of short half-life, positron-emitting isotopes. In this work, we examine the use of a pulse line ion accelerator (PLIA) to accelerate protons for single-dose PET isotope production. Methods Time-domain electromagnetic field and particle-in-cell (PIC) simulations were performed for a 1.5-m PLIA structure modeled in CST Microwave Studio and Particle Studio software. Scaled measurements from a kV ramp-pulse generator were incorporated into the simulations to accelerate a 1 A, 50 ns proton beam injected with initial kinetic energy of 100 keV. A uniform, 3 T, solenoidal magnetic field was used to provide external beam focusing. Electromagnetic fields and particle phase space were recorded with ns resolution for subsequent analysis. Results Applying a scaled 100 kV, 20 ns ramped voltage pulse to the PLIA input resulted in a travelling electric field wave inside the structure with accelerating gradient of 2.4 MV/m. The observed wave speed was 1.2 × 107 m/s and is in good agreement with theoretical predictions. Phase space monitors showed both acceleration and bunching of the proton beam, with a maximum kinetic energy of 2.5 MeV, observed at the exit of the single PLIA stage. Evaluation of beam position monitors at different locations in the accelerator showed bunch compression and minimal beam divergence, illustrating that the 3 T field is adequate to contain the beam over the length of the PLIA structure. Conclusion Simulations performed in this work demonstrate the feasibility of using a PLIA structure to accelerate protons with MV/m level gradients. Combining several PLIA stages in series could allow for a low-cost accelerator suitable for dose-on-demand PET isotope production.

PURPOSE Scattered radiation remains to be a major cause of image quality degradation in Flat Panel Detector (FPD)-based Cone-beam computed tomography (CBCT). We have been investigating a novel two-dimensional antiscatter grid (2D-ASG) concept to reduce scatter intensity, and hence improve CBCT image quality. We present the first CBCT imaging experiments performed with the 2D-ASG prototype, and demonstrate its efficacy in improving CBCT image quality. METHODS A 2D-ASG prototype with septa focused to x-ray source was additively manufactured from tungsten and mounted on a Varian TrueBeam CBCT system. CBCT projections of phantoms were acquired with an offset detector geometry using TrueBeam's "developer" mode. To minimize the effect of gantry flex, projections were gain corrected on angle-specific bases. CBCT images were reconstructed using a filtered backprojection algorithm and image quality improvement was quantified by measuring contrast-to-noise ratio (CNR) and CT number accuracy in images acquired with no antiscatter grid (NO-ASG), conventional one dimensional antiscatter grid (1D-ASG), and the 2D-ASG prototype. RESULTS A significant improvement in contrast resolution was achieved using our 2D-ASG prototype compared to results of 1D-ASG and NO-ASG acquisitions. Compared to NO-ASG and 1D-ASG experiments, the CNR of material inserts improved by as much as 86% and 54% respectively. Using 2D-ASG, CT number underestimation in water equivalent material section of the phantom was reduced by up to 325 HU when compared to NO-ASG and up to 179 HU when compared to 1D-ASG. CONCLUSION We successfully performed the first CBCT imaging experiments with a 2D-ASG prototype. 2D-ASG provided significantly higher CT number accuracy, higher CNR, and diminished scatter-induced image artifacts in qualitative evaluations. We strongly believe that utilization of a 2D-ASG may potentially lead to better soft tissue visualization in CBCT and may enable novel clinical applications that require high CT number accuracy.

Purpose/Objective(s) Ventilation-perfusion dose-response studies have focused on using functional imaging to characterize a dose-response and to assess whether the dose-response can predict subsequent pulmonary toxicity. Current dose-response studies typically focus on a single modality (ventilation or perfusion) and perform assessments on a population-based basis. There is no work evaluating whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. The purpose of this study was to use single photon emission computed tomography (SPECT)-CT ventilation-perfusion imaging to quantitatively and clinically evaluate whether lung cancer patients treated with radiotherapy have differences between their ventilation and perfusion dose-responses. Materials/Methods Twenty patients with biopsy proven lung cancer enrolled on a prospective functional avoidance protocol underwent SPECT-CT perfusion-ventilation scans pre- and 3-month post-radiotherapy. The SPECT-CT, planning CT, and dose distribution were rigidly registered. We calculated the relative changes in pre- to post-treatment ventilation-perfusion in lung regions receiving ≥ 20 Gy (referred to as ΔPV20 for perfusion and ΔVV20 for ventilation). Differences between perfusion-based ΔPV20 and ventilation-based ΔVV20 were assessed and referred to as ΔfV20. A radiologist read each pre- and post-treatment ventilation-perfusion scans using a semi-quantitative scale that assigned a score ranging from 1 to 8 that reflected functional defect and heterogeneity in each lung. The difference between radiologist scores for the pre- and post-treatment scans was calculated for both ventilation and perfusion. Differences between ventilation-based and perfusion-based radiologist scores were assessed. Results Twenty-five percent of patients had a difference of ΔfV20 > 35% between ventilation-perfusion pre- to post-treatment changes (ΔVV20 and ΔPV20) and 20% of patients had opposite directions for ventilation-perfusion pre- to post-treatment changes. Radiologist assessment resulted in 20% of patients having different ventilation-perfusion semi-quantitative change scores for ipsilateral lungs. Conclusion The current work employed quantitative metrics and clinical assessments to evaluate whether ventilation dose-response differs from perfusion dose-response for individual lung cancer patients. Our data showed that ventilation dose-response can differ from perfusion dose-response for 20% to 30% of patients. Our study demonstrates that when evaluating functional dose-response for lung cancer patients, it is insufficient to look at ventilation or perfusion alone for a subset of patients; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.

Stereotactic body radiation therapy (SBRT) for pancreatic cancer requires a skillful approach to deliver ablative doses to the tumor while limiting dose to the highly sensitive duodenum, stomach, and small bowel. Here, we develop knowledge-based artificial neural network dose models (ANN-DMs) to predict dose distributions that would be approved by experienced physicians. Using dose distributions calculated by a commercial treatment planning system (TPS), physician-approved treatment plans were used to train ANN-DMs that could predict physician-approved dose distributions based on a set of geometric parameters (vary from voxel to voxel) and plan parameters (constant across all voxels for a given patient). Differences between TPS and ANN-DM dose distributions were used to evaluate model performance. ANN-DM design, including neural network structure and parameter choices, were evaluated to optimize dose model performance. Mean dose errors were less than 5% at all distances from the PTV, and mean absolute dose errors were on the order of 5%, but no more than 10%. Dose-volume histogram errors demonstrated good model performance above 25 Gy, but much larger errors were seen at lower doses. ANN-DM dose distributions showed excellent overall agreement with TPS dose distributions, and accuracy was substantially improved when each physician's treatment approach was taken into account by training their own dedicated models. In this manner, one could feasibly train ANN-DMs that could predict the dose distribution desired by a given physician for a given treatment site., 11 pages, 6 figures

Aim High fraction of scattered radiation in cone-beam CT (CBCT) imaging degrades CT number accuracy and visualization of low contrast objects. To suppress scatter in CBCT projections, we developed a focused, two-dimensional antiscatter grid (2DASG) prototype. In this work, we report on the primary and scatter transmission characteristics of the 2DASG prototype aimed for linac mounted, offset detector geometry CBCT systems in radiation therapy, and compared its performance to a conventional one-dimensional ASG (1DASG). Methods The 2DASG is an array through-holes separated by 0.1 mm septa that was fabricated from tungsten using additive manufacturing techniques. Through-holes’ focusing geometry was designed for offset detector CBCT in Varian TrueBeam system. Two types of ASGs were evaluated: a) a conventional 1DASG with a grid ratio of 10, b) the 2DASG prototype with a grid ratio of 8.2. To assess the scatter suppression performance of both ASGs, Scatter-to-primary ratio (SPR) and scatter transmission fraction (Ts) were measured using the beam stop method. Scatter and primary intensities were modulated by varying the phantom thickness between 10 and 40 cm. Additionally, the effect of air gap and bow tie (BT) filter on SPR and Ts were evaluated. Average primary transmission fraction (TP) and pixel specific primary transmission were also measured for both ASGs. To assess the effect of transmission characteristics on projection image signal-to-noise ratio (SNR) improvement factor was calculated. Improvement in contrast to noise ratio (CNR) was demonstrated using a low contrast object. Results In comparison to 1DASG, 2DASG reduced SPRs by a factor of 3 to 6 across the range of phantom setups investigated. Ts values for 1D and 2DASGs were in the range of 21 to 29%, and 5 to 14%, respectively. 2DASG continued to provide lower SPR and Ts at increased air gap and with BT filter. Tp of 1D and 2DASGs were 70.6% and 84.7%, respectively. Due to the septal shadow of the 2DASG, its pixel specific primary transmission values varied between 32.5% and 99.1%. With respect to 1DASG, 2DASG provided up to factor of 1.7 more improvement in SNR across the SPR range investigated. Moreover, 2DASG provided improved visualization of low contrast objects with respect to 1DASG and NOASG setups. Conclusions When compared to a conventional 1DASG, 2DASG prototype provided noticeably lower SPR and Ts values, indicating its superior scatter suppression performance. 2DASG also provided 19% higher average primary transmission that was attributed to the absence of interseptal spacers and optimized grid geometry. Our results indicate that the combined effect of lower scatter and higher primary transmission provided by 2DASG may potentially translate into more accurate CT numbers and improved contrast resolution in CBCT images. This article is protected by copyright. All rights reserved.

Purpose: Implanted fiducial markers are often used in radiotherapy to facilitate accurate visualization and localization of tumors. Typically, such markers are used to aid daily patient positioning and to verify the target's position during treatment. This work introduces a novel, automated method for identifying fiducial markers in planar x-ray imaging. Methods: In brief, the method consists of automated filtration and reconstruction steps that generate 3D templates of marker positions. The normalized cross-correlation was the used to identify fiducial markers in projection images. To quantify the accuracy of the technique, a phantom study was performed. 75 pre-treatment CBCT scans of 15 pancreatic cancer patients were analyzed to test the automated technique under real life conditions, including several challenging scenarios for tracking fiducial markers. Results: In phantom and patient studies, the method automatically tracked visible marker clusters in 100% of projection images. For scans in which a phantom exhibited 0D, 1D, and 3D motion, the automated technique showed median errors of 39 $\mu$m, 53 $\mu$m, and 93 $\mu$m, respectively. Human precision was worse in comparison. Automated tracking was performed accurately despite the presence of other metallic objects. Additionally, transient differences in the cross-correlation score identified instances where markers disappeared from view. Conclusions: A novel, automated method for producing dynamic templates of fiducial marker clusters has been developed. Production of these templates automatically provides measurements of tumor motion that occurred during the CBCT scan that was used to produce them. Additionally, using these templates with intra-fractional images could potentially allow for more robust real-time target tracking in radiotherapy., Comment: 12 pages, 7 figures

Purpose Automatic detection and identification of setup devices, using a deep convolutional neural network (CNN) for real time multi-class object detection, has the potential to reduce errors in the treatment delivery process by avoiding documentation errors. Methods A database of the setup device photos from the most recent 1200 patients treated at our institution was downloaded from the record and verify system (R&V) along with the corresponding set-up notes. Images were manually labelled with bounding boxes of each device. A real time object detection CNN using the 'you only look once' (YOLOv2) architecture was trained using transfer learning of a pre-trained CNN (ResNet50). The CNN was trained to detect and identify 11 of the most common treatment accessories used at our institution. Results Using transfer learning of a CNN for multi-class object detection, we are able to automatically detect and identify set-up devices in photographs with an accuracy of 96%. Conclusions Automation in radiation oncology has the potential to reduce risk. Automatic detection of setup devices is possible using a CNN and transfer learning. This work shows both the value of incident learning systems (ILS) in practice knowledge dissemination, and shows how automation of clinical processes and less reliance on manual documentation has the potential for risk reduction in radiation oncology treatments.

The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18F-fluorodeoxyglucose ([ 18F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [ 18F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [ 18F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [ 18F]FDG-PET for RT.

Purpose This study aimed to identify the current state of residency training in physics plan reviews. Methods and Materials A voluntary, anonymous survey was sent to all program directors of accredited therapeutic medical physics residency programs in North America. Survey questions were developed to determine whether and how residents are trained in physics plan reviews. Survey questions were developed using expert validation and cognitive pretesting. Results Using a prospectively approved study (COMIRB 18-1073), responses were collected from 70 program directors, representing a 70% response rate. All respondents (100%) designated patient safety to be the purpose of physics plan reviews. Of the respondents, 94% indicated that physicists should first receive training in physics plan reviews while in a residency program. The vast majority of respondents (99%) provide training to residents in physics plan reviews. Although 57 programs (81% of respondents) have residents perform physics plan reviews as part of clinical practice (with varying levels of independence), 13 programs (19% of respondents) do not. The majority of respondents use the following training methods: observe staff physicists (96%), perform supervised reviews on actual patients for training or clinical practice (93%), use a checklist (80%), and read reference materials (62%). Although simulation plans with embedded errors would be implemented by 71% of respondents, they are currently used in only 19% of programs. Conclusions The present study is the first to characterize chart-check teaching practices in medical physics residency programs. The vast majority of programs currently train residents in physics plan reviews. The most common teaching methods are observing and performing physics plan reviews, but there is variability in the level of resident involvement in clinical practice for physics plan reviews. There is room for the field to consider advancing current training methods, which is especially important given the critical roles that physics plan reviews have with regard to patient safety.

PURPOSE: Internal organ motion reduces the accuracy and efficacy of radiation therapy. However, there is a lack of tools to objectively (based on a medical or scientific task) assess the dosimetric consequences of motion, especially on an individual basis. We propose to use therapy operating characteristic (TOC) analysis to quantify the effects of motion on treatment efficacy for individual patients. We demonstrate the application of this tool with pancreatic stereotactic body radiation therapy (SBRT) clinical data and explore the origin of motion sensitivity. METHODS: The technique is described as follows. (1) Use tumor-motion data measured from patients to calculate the motion-convolved dose of the gross tumor volume (GTV) and the organs at risk (OARs). (2) Calculate tumor control probability (TCP) and normal tissue complication probability (NTCP) from the motion-convolved dose volume histograms. (3) Construct TOC curves from TCP and NTCP models. (4) Calculate the area under the TOC curve (AUTOC) and use it as a figure of merit for treatment efficacy. We used tumor motion data measured from patients to calculate the relation between AUTOC and motion magnitude for 25 pancreatic SBRT treatment plans. Furthermore, to explore the driving factor of motion sensitivity of a given plan, we compared the dose distribution of motion-sensitive plans and motion-robust plans and studied the dependence of motion sensitivity to motion directions. RESULTS: Our technique is able to recognize treatment plans that are sensitive to motion. Under the presence of motion, the treatment efficacy of some plans changes from providing high tumor control and low risks of complications to providing no tumor control and high risks of side effects. Several treatment plans experience falloffs in AUTOC at a smaller magnitude of motion than other plans. In our dataset, a potential indicator of a motion-sensitive treatment plan is that the duodenum is in close proximity to the tumor in the SI direction. CONCLUSIONS: The TOC framework can serve as a tool to quantify the effects of internal organ motion in radiation therapy. With pancreatic SBRT clinical data, we applied this tool to study the change in treatment efficacy induced by motion for individual treatment plans. This framework could potentially be used clinically to understand the effects of motion in an individual patient and to design a patient-specific motion management plan. This framework could also be used in research to evaluate different components of the treatment process, such as motion-management techniques, treatment-planning algorithms, treatment margins, etc.

The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is

Managing radiotherapy patients with implanted cardiac devices (implantable cardiac pacemakers and implantable cardioverter-defibrillators) has been a great practical and procedural challenge in radiation oncology practice. Since the publication of the AAPM TG-34 in 1994, large bodies of literature and case reports have been published about different kinds of radiation effects on modern technology implantable cardiac devices and patient management before, during, and after radiotherapy. This task group report provides the framework that analyzes the potential failure modes of these devices and lays out the methodology for patient management in a comprehensive and concise way, in every step of the entire radiotherapy process.

Purpose Numerous dose and fractionation schedules have been used to treat medically inoperable stage I non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy. We evaluated published experiences with SBRT to determine local control (LC) rates as a function of SBRT dose. Methods and Materials One hundred sixty published articles reporting LC rates after SBRT for stage I NSCLC were identified. Quality of the series was assessed by evaluating the number of patients in the study, homogeneity of the dose regimen, length of follow-up time, and reporting of LC. Clinical data including 1, 2, 3, and 5-year tumor control probabilities for stages T1, T2, and combined T1 and T2 as a function of the biological effective dose were fitted to the linear quadratic, universal survival curve, and regrowth models. Results Forty-six studies met inclusion criteria. As measured by the goodness of fit χ2/ndf, with ndf as the number of degrees of freedom, none of the models were ideal fits for the data. Of the 3 models, the regrowth model provides the best fit to the clinical data. For the regrowth model, the fitting yielded an α-to-β ratio of approximately 25 Gy for T1 tumors, 19 Gy for T2 tumors, and 21 Gy for T1 and T2 combined. To achieve the maximal LC rate, the predicted physical dose schemes when prescribed at the periphery of the planning target volume are 43 ± 1 Gy in 3 fractions, 47 ± 1 Gy in 4 fractions, and 50 ± 1 Gy in 5 fractions for combined T1 and T2 tumors. Conclusions Early-stage NSCLC is radioresponsive when treated with SBRT or stereotactic ablative radiation therapy. A steep dose-response relationship exists with high rates of durable LC when physical doses of 43-50 Gy are delivered in 3 to 5 fractions.

Purpose Motion often hinders the safe delivery of ablative doses of radiation in the treatment of pancreatic tumors. Real-time tumor-tracking methods are an emerging technique to increase the accuracy of delivery. In this study, we report on a large, retrospective cohort of pancreatic patients treated with real-time, fiducial-based, kV-image guidance of stereotactic body radiation therapy (SBRT). The purpose of our study was to determine the impact of real-time tracking on treatment accuracy, tumor dose, and clinical workflow. Methods and Materials Real-time tracking data from 68 patients treated with pancreatic SBRT were analyzed. The kV images orthogonal to the treatment beam were acquired in real time during treatment to visualize the location of implanted fiducial markers. Positional corrections were made if the fiducial markers were observed >3 mm from the expected reference position. We recorded the frequency and nature of treatment interventions resulting from real-time tracking and derived a neural network–based dosimetric model to calculate the impact of these in-treatment interventions on target dose. Results Treatment pauses that required patient realignment because of real-time tumor tracking occurred during 32% of all fractions. The median magnitude of realignment shifts was 5.2 mm (range, 2.1-18.9 mm). Forty-five percent of shifts resulted in dosimetric differences to the tumor; of these, the median point dose difference was 23% ± 22% of prescription dose (maximum, 94%). The number of pauses per fraction was significantly higher in patients treated with respiratory gating (vs abdominal compression) and in patients with greater treatment time. Conclusion Fiducial-based, real-time target tracking is clinically feasible for pancreatic SBRT treatment. Our data indicate that real-time tumor tracking leads to patient realignment in 32% of cases and results in significant benefits to target coverage. The increased accuracy of real-time target tracking may potentially enable safe dose escalation in pancreatic SBRT.

PURPOSE: Patients with esophageal cancer treated with chemoradiation and surgery can develop pulmonary complications. Four-dimensional computed tomography–ventilation (4DCT-ventilation) is a developing imaging modality that uses 4DCT data to calculate lung ventilation. 4DCT-ventilation has been studied in the lung-cancer population but has yet to be extended to patients with esophageal cancer. The purpose of this study was to characterize 4DCT-ventilation–based spatial lung function for patients with esophageal cancer. METHODS AND MATERIALS: Thirty-five patients with esophageal cancer who underwent 4DCT scans participated in the study. A 4DCT-ventilation map was calculated using the patient’s 4DCT imaging and a density change–based algorithm. To assess each patient’s ventilation profile, radiologist interpretations and quantitative metrics were used. A radiologist interpreted the 4DCT-ventilation images for lobar-based defects and gravity-dependent atelectasis. The 4DCT-ventilation maps were reduced to single metrics intended to reflect the degree of ventilation heterogeneity. The quantitative metrics included the coefficient of variation and metrics based on the ventilation in each lung and each lung third (superior-inferior ventilation [Vent-SI] and anteroposterior ventilation). The functional profile of patients with esophageal cancer was characterized and compared (using the Mann-Whitney test) for cohorts based on thoracic comorbidities and radiologist-identified defects. RESULTS: Radiologist observations revealed that 26% of patients with esophageal cancer had lobar-based defects and 46% had gravity-dependent atelectasis. The baseline values were 0.52 ± 0.20 (mean ± SD), 11.2 ± 12.5, and 72.5 ± 14.6 for the coefficient of variation, the ventilation ratio of right to left lung, and Vent-SI metrics, respectively. The Vent-SI values were significantly different between patients with and without thoracic comorbidities (P = .05), and the anteroposterior ventilation metric was able to delineate patients with and without gravity-dependent atelectasis (P < .01). CONCLUSIONS: Our data demonstrate that approximately 30% of patients with esophageal cancer have significant ventilation heterogeneities. The current work uses radiologist observations and quantitative metrics to characterize 4DCT ventilation–based lung function for patients with esophageal cancer and presents data that can be used for future applications of 4DCT-ventilation to reduce thoracic toxicity for patients with esophageal cancer. © 2018 Elsevier Inc. All rights reserved.

Purpose Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Methods The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. Results Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. Conclusion Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions.

Purpose A form of lung functional imaging has been developed that uses 4DCT data to calculate ventilation (4DCT‐ventilation). Because 4DCTs are acquired as standard‐of‐care to manage breathing motion during radiotherapy, 4DCT‐ventilation provides functional information at no extra dosimetric or monetary cost. 4DCT‐ventilation has yet to be described in children. 4DCT‐ventilation can be used as a tool to help assess post‐treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT‐ventilation‐based lung function changes for pediatric patients receiving radiotherapy to the lungs. Methods The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density‐change‐based algorithm were used to compute pre and post‐treatment 4DCT‐ventilation images. The post‐treatment 4DCT‐ventilation images were compared to the pretreatment 4DCT‐ventilation images for a global lung response and for an intrapatient dose–response (providing an assessment for dose‐dependent regional dose–response). Results For three of the four patients, a global ventilation decline of 7–37% was observed, while one patient did not demonstrate a global functional decline. Dose–response analysis did not reveal an intrapatient dose–response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT‐ventilation decline as a function of increasing lung doses up to 50 Gy. Conclusions Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT‐ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging‐based early changes can be predicted for long‐term clinical toxicity.

PURPOSE: To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. METHODS AND MATERIALS: We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (100 Gy(10)). Comparisons were made using logerank testing. RESULTS: Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, logerank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy(10) (3-year local control 93%) than for those treated with BEDs of 100 Gy(10) (3-year local control 65%, P < .001). CONCLUSIONS: Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a doseeresponse relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy(10) are utilized.

PURPOSE: Functional imaging has been proposed that uses 4DCT images to calculate 4DCT-based lung ventilation (4DCT-ventilation). We have started a 2-institution, phase 2 prospective trial evaluating the feasibility, safety, and preliminary efficacy of 4DCT-ventilation functional avoidance. The trial hypothesis is that the rate of grade ≥2 radiation pneumonitis could be reduced to 12% with functional avoidance, compared with a 25% rate of pneumonitis with a historical control. The trial employed a Simon 2-stage design with a planned futility analysis after 17 evaluable patients. The purpose of this work is to present the trial design and implementation, dosimetric data, and clinical results for the planned futility analysis. METHODS AND MATERIALS: Eligible patients were patients with lung cancer who were prescribed doses of 45 to 75 Gy. For each patient, the 4DCT data were used to generate a 4DCT-ventilation image using the Hounsfield unit technique along with a compressible flow-based image registration algorithm. Two intensity modulated radiation therapy treatment plans were generated: (1) a standard lung plan and (2) a functional avoidance treatment plan that aimed to reduce dose to functional lung while meeting target and normal tissue constraints. Patients were treated with the functional avoidance plan and evaluated for thoracic toxicity (presented as rate and 95% confidence intervals [CI]) with a 1-year follow-up. RESULTS: The V20 to functional lung was 21.6% ± 9.5% (mean ± standard deviation) with functional avoidance, representing a decrease of 3.2% (P < .01) relative to standard, nonfunctional treatment plans. The rates of grade ≥2 and grade ≥3 radiation pneumonitis were 17.6% (95% CI, 3.8%−43.4%) and 5.9% (95% CI, 0.1%−28.7%), respectively. CONCLUSIONS: Dosimetrically, functional avoidance achieved reduction in doses to functional lung while meeting target and organ at risk constraints. On the basis of Simon’s 2-stage design and the 17.6% grade ≥2 pneumonitis rate, the trial met its futility criteria and has continued accrual.

Purpose A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Methods and Materials Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change–based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. Results Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. Conclusions Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.

Purpose: Cone-beam CT (CBCT) projection images provide anatomical data in real-time over several respiratory cycles, forming a comprehensive picture of tumor movement. We developed and validated a method which uses these projections to determine the trajectory of and dose to highly mobile tumors during each fraction of treatment. Methods: CBCT images of a respiration phantom were acquired, the trajectory of which mimicked a lung tumor with high amplitude (up to 2.5 cm) and hysteresis. A template-matching algorithm was used to identify the location of a steel BB in each CBCT projection, and a Gaussian probability density function for the absolute BB position was calculated which best fit the observed trajectory of the BB in the imager geometry. Two modifications of the trajectory reconstruction were investigated: first, using respiratory phase information to refine the trajectory estimation (Phase), and second, using the Monte Carlo (MC) method to sample the estimated Gaussian tumor position distribution. Results: With all methods, the mean position of the BB was determined with accuracy better than 0.1 mm, and trajectory errors averaged 3.8$\pm$1.1% of the marker amplitude. Dosimetric calculations using Phase methods were more accurate, with mean absolute error less than 0.5%, and with error less than 1% in the highest-noise trajectory. MC-based trajectories prevent the over-estimation of dose, but when viewed in an absolute sense, add a small amount of dosimetric error (

Background and purpose There are two significant challenges when implementing functional-guided radiotherapy using 4DCT-ventilation imaging: (1) lack of knowledge of realistic patient specific dosimetric goals for functional lung and (2) ensuring consistent plan quality across multiple planners. Knowledge-based planning (KBP) is positioned to address both concerns. Material and methods A KBP model was created from 30 previously planned functional-guided lung patients. Standard organs at risk (OAR) in lung radiotherapy and a ventilation contour delineating areas of high ventilation were included. Model validation compared dose-metrics to standard OARs and functional dose-metrics from 20 independent cases that were planned with and without KBP. Results A significant improvement was observed for KBP optimized plans in V20Gy and mean dose to functional lung (p = 0.005 and 0.001, respectively), V20Gy and mean dose to total lung minus GTV (p = 0.002 and 0.01, respectively), and mean doses to esophagus (p = 0.005). Conclusion The current work developed a KBP model for functional-guided radiotherapy. Modest, but statistically significant, improvements were observed in functional lung and total lung doses.

Background With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. Aims This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. Materials & methods We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. Results We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Discussion Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Conclusion Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA.The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented.Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined.Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions.

Purpose: To study the imageeffects of the time‐wise dynamic aspect of intravenous contrast agents to enable contrast‐enhanced cone‐beam CT (CE‐ CBCT) localization of liver lesions for stereotactic body radiation therapy(SBRT).Methods: A model was developed to study dynamic IV contrast agents using static phantoms and to derive optimum parameters for CE‐ CBCTimaging. Ten samples containing iodine at 0–5 mg/mL were prepared in cylindrical tubes, corresponding roughly to 0–100 HU as measured by 120 kV helical CTimaging. Each sample was imaged separately in a tissue‐ equivalent phantom, yielding ten datasets (roughly 650 projections each) corresponding to these static CBCTimages. To reconstructimages of dynamic contrast concentrations, the CBCT 2D projections were re‐ assembled to match the expected amount of contrast at different points in time. This model was applied to published hepatic contrast enhancement curves, and optimum imaging and contrast injection parameters were derived. Results: A signal‐to‐noise ratio (SNR) decrease of 25%–75% in dynamic CE‐CBCT images from ideal CT of samples with a 20–100 HU difference from water was observed in the un‐optimized scans. This demonstrates the difficulty of CE‐CBCT, and was noticed even in geometries that minimize or eliminate x‐ray scatter, detector glare, and motion. Using our model, we found parameters for iodine injection, CBCT scanning, and injection/scanning timing which optimize contrast enhancement, and a 100% SNR increase with respect to the un‐optimized scans was achieved. Conclusions: The effect of IV contrast is severely degraded in CBCT, and optimization of image and timing parameters is crucial for improved CE‐CBCT imaging for target localization. CBCT has very low temporal resolution, and the pharmacokinetics of IV contrast must be carefully considered in order to apply this technique to localize liver lesions for SBRT. This model will be used to establish the feasibility of CE‐ CBCT for routine localization of liver lesions.

Purpose: Plan report documentation contains numerous details about the treatment plan, but critical information for patient safety is often presented without special emphasis. This can make it difficult to detect errors from treatment planning and data transfer during the initial chart review. The objective of this work is to improve safety measures in radiation therapy practice by customizing the treatment plan report to emphasize safety‐critical information. Methods: Commands within the template file from a commercial planning system (Eclipse, Varian Medical Systems) that automatically generates the treatment plan report were reviewed and modified. Safety‐critical plan parameters were identified from published risks known to be inherent in the treatment planning process. Risks having medium to high potential impact on patient safety included incorrect patient identifiers, erroneous use of the treatment prescription, and incorrect transfer of beam parameters or consideration of accessories. Specific examples of critical information in the treatment plan report that can be overlooked during a chart review included prescribed dose per fraction and number of fractions, wedge and open field monitor units, presence of beam accessories, and table shifts for patient setup. Results: Critical information was streamlined and concentrated. Patient and plan identification, dose prescription details, and patient positioning couch shift instructions were placed on the first page. Plan information to verify the correct data transfer to the record and verify system was re‐organized in an easy to review tabular format and placed in the second page of the customized printout. Placeholders were introduced to indicate both the presence and absence of beam modifiers. Font sizes and spacing were adjusted for clarity, and departmental standards and terminology were introduced to streamline data communication among staff members. Conclusions: Plan reporting documentation has been customized to concentrate and emphasize safety‐critical information, which should allow for a more efficient, robust chart review process.