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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose 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. Methods Arc-based SBRT treatment plans for 43 pancreatic cancer patients were planned, delivering 30-33 Gy in five fractions. Treatments were overseen by one of two physicians with individual treatment approaches, with variations in prescribed dose, target volume delineation, and primary organs at risk. 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). Patient datasets were randomly allocated, with two-thirds used for training, and one-third used for validation. Differences between TPS and ANN- DM dose distributions were used to evaluate model performance. ANN- DM design, including neural network structure and parameter choices, was evaluated to optimize dose model performance. Results Remarkable improvements in ANN- DM accuracy (i.e., from > 30% to < 5% mean absolute dose error, relative to the prescribed dose) were achieved by training separate dose models for the treatment style of each physician. Increased neural network complexity (i.e., more layers, more neurons per layer) did not improve dose model accuracy. 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 (in cm3) demonstrated good model performance above 25 Gy, but much larger errors were seen at lower doses. Conclusions 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. [ABSTRACT FROM AUTHOR]

Background: Quantitative accuracy is critical for expanding the role of cone beam CT (CBCT) imaging from target localization to quantitative treatment monitoring and plan adaptations in radiation therapy. Despite advances in CBCT image quality improvement methods, quantitative accuracy gap between CBCT and multi‐detector CT (MDCT) remains. Purpose: In this work, a physics‐driven approach was investigated that combined robust scatter rejection, raw data correction and iterative image reconstruction to further improve CBCT image quality and quantitative accuracy, referred to as quantitative CBCT (qCBCT). Methods: QCBCT approach includes tungsten 2D antiscatter grid hardware, residual scatter correction with grid‐based scatter sampling, image lag, and beam hardening correction for offset detector geometry linac‐mounted CBCT. Images were reconstructed with iterative image reconstruction to reduce image noise. qCBCT was evaluated using a variety of phantoms to investigate the effect of object size and its composition on image quality, and image quality was benchmarked against clinical CBCT and gold standard MDCT images used for treatment planning. Results: QCBCT provided statistically significant improvement in CT number accuracy and reduced image artifacts when compared to clinical CBCT images. When compared to gold standard MDCT, mean HU errors in qCBCT and clinical CBCT were 17 ± 9 and 38 ± 29 HU, respectively. Magnitude of phantom size dependent HU variations were comparable between MDCT and qCBCT images. With iterative reconstruction, contrast‐to‐noise ratio improved by 25% when compared to clinical CBCT protocols. Conclusions: Combination of novel scatter suppression techniques and other data correction methods in qCBCT provided CT number accuracy comparable to gold standard MDCT used for treatment planning. This approach may potentially improve CBCT's promise in fulfilling the tasks that demand high quantitative accuracy, such as online dose calculations and treatment response assessment, in image guided radiation therapy. [ABSTRACT FROM AUTHOR]

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. These markers can also provide a wealth of information regarding tumor motion, yet determining their accurate position in thousands of images is often prohibitive. This work introduces a novel, automated method for identifying fiducial markers in planar x-ray imaging. Methods In brief, the method was performed as follows. First, using processed CBCT projection images, an automated routine of reconstruction, forward-projection, tracking, and stabilization generated static templates of the marker cluster at arbitrary viewing angles. Breathing data were then incorporated into the same routine, resulting in dynamic templates dependent on both viewing angle and breathing motion. Finally, marker clusters were tracked using normalized cross correlations between templates (either static or dynamic) and CBCT projection images. To quantify the accuracy of the technique, a phantom study was performed and markers were manually tracked by two users to compare the automated technique against human measurements. Then, 75 pretreatment 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 (e.g., extraneous metallic objects, field-of-view limitations, and marker migration). Results In phantom and patient studies, for both static and dynamic templates, 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 μm, 53 μm, and 93 μm, respectively. Human precision was worse in comparison; median interobserver differences for single markers and for the averaged coordinates of four markers were 183 μm and 120 μm, respectively. In patient scans, the method was robust against a number of confounding factors. Automated tracking was performed accurately despite the presence of radio-opaque, nonmarker objects (e.g., metallic stents, surgical clips) in five patients. This success was attributed to the distinct appearance of clusters as a whole compared to individual markers. Dynamic templates produced higher cross-correlation scores than static templates in patients whose fiducial marker clusters exhibited considerable deformation or rotation during the breathing cycle. For other patients, no significant difference was seen between dynamic and static templates. 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 intrafractional images could potentially allow for more robust real-time target tracking in radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were created for the prechemotherapy and postchemotherapy scans so as to deliver 60Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1cc (7.3 to 351.6cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT. [Copyright &y& Elsevier]

The online image-guided localization data from 696 ultrasound (US), 598 mega-voltage cone-beam computed tomography (MV-CBCT), and 393 seed markers (SMs) couch alignments for patients undergoing intensity modulation radiotherapy of the prostate were analyzed. Daily US, MV-CBCT and SM images were acquired for 19, 17 and 12 patients, respectively, after each patient was immobilized in a vacuum cradle and setup to skin markers as the center of mass. The couch shifts applied in the lateral (left-right/LR), vertical (anterior-posterior/AP), and longitudinal (superior-inferior/SI) directions, along with the magnitude of the three-dimensional (3D) shift vector, were analyzed and compared for all three methods. The percentage of shifts larger than 5 mm in all directions was also compared. Clinical target volume-planning target volume (CTV-to-PTV) expansion margins were estimated based on the localization data with US, CB, and SM image guidance. Results show the US data have greater variability. Systematic and random shifts were -1.2±6.8 mm (LR), -2.8±5.1 mm (SI) and -1.0±5.9 mm (AP) for US, 1.0±3.9 mm (LR), -1.3±2.5 mm (SI) and -0.3±3.9 mm (AP) for CB, and -1.0±3.4 mm (LR), 0.0±3.4 mm (SI) and 0.5±4.1 mm (AP) for SM. The mean 3D shift distance was larger using US (8.8±6.2 mm) compared to CB and SM (5.3±3.4 mm and 5.2±3.7 mm, respectively). The percentage of US shifts larger than 5 mm were 34%, 31%, and 38% in the LR, SI, and AP directions, respectively, compared to 18%, 6%, and 16% for CB and 14%, 10%, and 20% for SM. MV-CBCT and SM localization data suggest a different distribution of prostate center-of-mass shifts with smaller variability, compared to US. The online MV-CBCT and SM image-guidance data show that for treatments that do not include daily prostate localization, one can use a CTV-to-PTV margin that is 4 mm smaller than the one suggested by US data, hence allowing more rectum and bladder sparing and potentially improving the therapeutic ratio. [ABSTRACT FROM AUTHOR]

The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200° gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6±1.0 Gy for the bladder and comparable for the rectum (-0.3±1.4 Gy). In addition, an average mean dose increase of 1.9±0.8 Gy in the femoral heads and 1.7±0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3±1.5% and 2.4±2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required. [ABSTRACT FROM AUTHOR]

The improvement in conformal radiotherapy techniques with steep dose gradients has allowed for the delivery of higher doses to a tumor volume while maintaining the sparing of surrounding normal tissue. In this situation, verification of patient setup and evaluation of internal organ motion just prior to radiation delivery is a crucial step. To this end, several volumetric image-guided techniques have been developed for patient localization, such as the Siemens MVision mega-voltage cone beam CT (MV-CBCT) system. In this work, the commissioning and clinical implementation of the MVision system is presented. The geometry and gain calibration procedures for the system are described, and guidelines for quality assurance procedures are provided. Different MV-CBCT clinical protocols, ranging from daily to weekly image-guidance, which includes image acquisition, reconstruction, registration with planning CT, and treatment couch offsets corrections, were commissioned. The image quality characteristics of the MVision system were measured and assessed qualitatively and quantitatively, including the image noise and uniformity, low-contrast resolution, and spatial resolution. Furthermore, the image reconstruction and registration software was evaluated. Data show that a 2 cm large object with 1% electron density contrast can be detected with the MVision system with 10 cGy at isocenter and that the registration software is accurate within 2 mm in the anterior-posterior, left-right, and superior-inferior directions. [ABSTRACT FROM AUTHOR]

In modern conformal radiotherapy (CRT), we attempt to increase its therapeutic ratio, thus improving the survival chances and/or quality of life for patients. It is common to acknowledge that poor local tumor control or increased normal tissue complications may arise from inaccurate targeting of the tumor, failure to conform the high-dose distribution to the target volume, and inaccurately delivered radiation doses. A further cause for concern is the influence that errors or inaccuracies in the dose calculation may have on the management of radiation therapy. Such errors arise from inherent limitations in the calculation algorithm used, which are more significant in some anatomical sites than others. Furthermore, an estimate of the therapeutic ratio is given by the ratio of tumor control probability (TCP) and normal tissue complication probability (NTCP). The effectiveness of these predictive indicators also depends on the accuracy of the calculated dose distributions in the target and surrounding normal structures. In this work, we compared CRT dose distributions of plans for the treatment of prostate, head-and-neck, and lung tumors using the measurement-based Clarkson and model-based Superposition dose calculation algorithms. Dose-volume histograms (DVHs) for the planning target volume (PTV) and sensitive structures, as well as NTCP and TCP, were compared. Dose distributions, observed in the lung and head-and-neck plans, vary significantly with respect to dose conformity as a function of algorithm used. Differences in the calculated maximum dose of up to 14% were observed in the PTV and sensitive structures for the lung and head-and-neck Clarkson-based plans, respectively, compared to the Superposition-based plans. Furthermore, a difference in the biological outcomes of up to 14% in the NTCP and 4% in the TCP was noticed. The CRT plans show the importance of accurate modeling of the effect of tissue inhomogeneities on dose distributions in the target and critical structures for lung and head-and-neck treatments. [Copyright &y& Elsevier]

A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P >.053). The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance. [ABSTRACT FROM AUTHOR]

Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure. [ABSTRACT FROM AUTHOR]

Background: Online dose calculations before the delivery of radiation treatments have applications in dose delivery verification, online adaptation of treatment plans, and simulation‐free treatment planning. While dose calculations by directly utilizing CBCT images are desired, dosimetric accuracy can be compromised due to relatively lower HU accuracy in CBCT images. Purpose: In this work, we propose a novel CBCT imaging pipeline to enhance the accuracy of CBCT‐based dose calculations in the pelvis region. Our approach aims to improve the HU accuracy in CBCT images, thereby improving the overall accuracy of CBCT‐based dose calculations prior to radiation treatment delivery. Methods: An in‐house developed quantitative CBCT pipeline was implemented to address the CBCT raw data contamination problem. The pipeline combines algorithmic data correction strategies and 2D antiscatter grid‐based scatter rejection to achieve high CT number accuracy. To evaluate the effect of the quantitative CBCT pipeline on CBCT‐based dose calculations, phantoms mimicking pelvis anatomy were scanned using a linac‐mounted CBCT system, and a gold standard multidetector CT used for treatment planning (pCT). A total of 20 intensity‐modulated treatment plans were generated for five targets, using 6 and 10 MV flattening filter‐free beams, and utilizing small and large pelvis phantom images. For each treatment plan, four different dose calculations were performed using pCT images and three CBCT imaging configurations: quantitative CBCT, clinical CBCT protocol, and a high‐performance 1D antiscatter grid (1D ASG). Subsequently, dosimetric accuracy was evaluated for both targets and organs at risk as a function of patient size, target location, beam energy, and CBCT imaging configuration. Results: When compared to the gold‐standard pCT, dosimetric errors in quantitative CBCT‐based dose calculations were not significant across all phantom sizes, beam energies, and treatment sites. The largest error observed was 0.6% among all dose volume histogram metrics and evaluated dose calculations. In contrast, dosimetric errors reached up to 7% and 97% in clinical CBCT and high‐performance ASG CBCT‐based treatment plans, respectively. The largest dosimetric errors were observed in bony targets in the large phantom treated with 6 MV beams. The trends of dosimetric errors in organs at risk were similar to those observed in the targets. Conclusions: The proposed quantitative CBCT pipeline has the potential to provide comparable dose calculation accuracy to the gold‐standard planning CT in photon radiation therapy for the abdomen and pelvis. These robust dose calculations could eliminate the need for density overrides in CBCT images and enable direct utilization of CBCT images for dose delivery monitoring or online treatment plan adaptations before the delivery of radiation treatments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To suppress scatter in cone beam computed tomography (CBCT), two-dimensional antiscatter grids (2D grid) have been recently proposed. In this work, we developed several grid prototypes with higher grid ratios and smaller grid pitches than previous designs, and quantified their primary and scatter transmission properties in the context of CBCT for radiation therapy. Three focused 2D grid prototypes were developed with grid ratios at 12 and 16, and grid pitches at 2 and 3 mm. Their scatter transmission properties were measured between 80–140 kVp, and benchmarked against a high performance radiographic grid (1D grid) using a Varian TrueBeam CBCT system. The effect of source–grid misalignment on the primary transmission and the improvement in contrast-to-noise ratio (CNR) were also evaluated. Changing the grid pitch from two to three mm increased the average primary transmission from 84% to 89%. Maximum scatter-to-primary ratio (SPR) with grid ratio of 12 was 0.3, and increasing the grid ratio to 16 reduced SPR by 30%. A 10 mm misalignment in 2D grid position led to a 6%–8% reduction in average primary transmission, and reduction was more pronounced for the higher grid ratio. 2D grids provided up to factor of seven lower SPR and 21% better primary transmission than the 1D grid, and their scatter transmission exhibited lower energy dependence. While 2D grids provided up to factor of 2.3 higher CNR improvement, a significant variation in CNR improvement was not observed among different grid pitch and ratios. In summary, grid ratio of 16 and grid pitch of 2 mm can keep SPRs below 0.2 even in high scatter conditions, while keeping primary transmission fractions above 80%, key benefits of the investigated 2D grids in improving image quality of CBCT. However, such grids require precise alignment in source-grid geometry during CBCT acquisitions. This study also implies that 2D grids can provide substantially better scatter suppression and primary transmission than high-performance 1D grids currently available. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose Recent studies suggest that 4DCT is unable to accurately measure respiratory-induced pancreatic tumor motion. In this work, we assessed the daily motion of pancreatic tumors treated with SBRT, and developed adaptive strategies to predict and account for this motion. Materials and methods The daily motion trajectory of pancreatic tumors during CBCT acquisition was calculated using a model which reconstructs the instantaneous 3D position in each 2D CBCT projection image. We developed a metric (termed “Spectral Coherence,” SC) based on the Fourier frequency spectrum of motion in the SI direction, and analyzed the ability of SC to predict motion-based errors and classify patients according to motion characteristics. Results The amplitude of daily motion exceeded the predictions of pre-treatment 4DCT imaging by an average of 3.0 mm, 2.3 mm, and 3.5 mm in the AP/LR/SI directions. SC was correlated with daily motion differences and tumor dose coverage. In a simulated adaptive protocol, target margins were adjusted based on SC, resulting in significant increases in mean target D95, D99, and minimum dose. Conclusion Our Fourier-based approach differentiates between consistent and inconsistent motion characteristics of respiration and correlates with daily motion deviations from pre-treatment 4DCT. The feasibility of an SC-based adaptive protocol was demonstrated, and this patient-specific respiratory information was used to improve target dosimetry by expanding coverage in inconsistent breathers while shrinking treatment volumes in consistent breathers. [ABSTRACT FROM AUTHOR]

Purpose: Cone-beam CT (CBCT) projection images provide anatomical data in real-time over several respiratory cycles, forming a comprehensive picture of tumor movement. The authors 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. The accuracies of the proposed methods were evaluated by comparing the known and calculated BB trajectories in phantom-simulated clinical scenarios using abdominal tumor volumes. Results: With all methods, the mean position of the BB was determined with accuracy better than 0.1 mm, and root-mean-square trajectory errors averaged 3.8% ± 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 overestimation of dose, but when viewed in an absolute sense, add a small amount of dosimetric error (<0.1%). Conclusions: Marker trajectory and target dose-of-the-day were accurately calculated using CBCT projections. This technique provides a method to evaluate highly mobile tumors using ordinary CBCT data, and could facilitate better strategies to mitigate or compensate for motion during stereotactic body radiotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast. Methods and materials: Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkin''s disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkin''s disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400cGy at 340cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5–60.3%) of the prescribed dose. Results: With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard. Conclusions: Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients. [Copyright &y& Elsevier]

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 (QA). We discuss the role of secondary dose/MU calculation programs as part of a comprehensive 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 QA; and on clinically reasonable action levels for agreement of secondary dose/MU calculation programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Gy10 vs >100 Gy10). Comparisons were made using log-rank 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, log-rank 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 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (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 dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic 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 Materials: This 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.Results: Ninety-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 <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8 Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20 Gy (V20) <10% to 15%.Conclusions: To allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Automatic detection and identification of setup devices, using a deep convolutional neural network (CNN) for real‐time multiclass 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 (R&V) system along with the corresponding setup notes. Images were manually labeled 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 pretrained 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 multiclass object detection, we are able to automatically detect and identify setup 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. (a) 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). (b) Calculate tumor control probability (TCP) and normal tissue complication probability (NTCP) from the motion‐convolved dose–volume histograms. (c) Construct TOC curves from TCP and NTCP models. (d) 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 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, and treatment margins. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

• The study aimed to evaluate which clinical, dose, and dose-function factors predict pulmonary function test (PFT) changes for patients with lung cancer treated with 4DCT-ventilation functional avoidance radiotherapy. • Results showed that only dose-function metrics and the presence of COPD were significant in predicting FEV1 decline through univariate analysis. • Multivariate analysis identified a combination of clinical factors and dose-function metrics in predicting FEV1 and FEV1/FVC changes. • The study validated the significance of reducing dose to functional lung to mitigate decline in pulmonary function and provided guidance for future clinical trials. Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Four-dimensional (4D) computed tomography (CT) ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiation therapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP).Methods and Materials: Seventy lung cancer patients who underwent 4D CT imaging and pneumonitis grading were assessed. Pretreatment 4D CT scans of each patient were used to calculate ventilation images. We evaluated 3 types of dose-function metrics that combined the patient's 4D CT ventilation image and treatment planning dose distribution: (1) structure-based approaches; (2) image-based approaches using the dose-function histogram; and (3) nonlinear weighting schemes. Log-likelihood methods were used to generate normal tissue complication probability models predicting grade 3 or higher (ie, grade 3+) pneumonitis for all dose-function schemes. The area under the curve (AUC) was used to assess the predictive power of the models. All techniques were compared with normal tissue complication probability models based on traditional, total lung dose metrics.Results: The most predictive models were structure-based approaches that focused on the volume of functional lung receiving ≥20 Gy (AUC, 0.70). Probabilities of grade 3+ RP of 20% and 10% correspond to V20 (percentage of volume receiving ≥20 Gy) to the functional subvolumes of 26.8% and 9.3%, respectively. Imaging-based analysis with the dose-function histogram and nonlinear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when we evaluated the percentage of functionality receiving ≥20 Gy. All dose-function metrics outperformed the traditional dose metrics (mean lung dose, AUC of 0.55).Conclusions: A full range of dose-function metrics and functional thresholds was examined. The calculated AUC values for the most predictive functional models occupied a narrow range (0.66-0.70), and all showed notable improvements over AUC from traditional lung dose metrics (0.55). Identifying the combinations most predictive of grade 3+ RP provides valuable data to inform the functional-guided radiation therapy process. [ABSTRACT FROM AUTHOR]

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 (2 DASG) prototype. In this work, we report on the primary and scatter transmission characteristics of the 2 DASG prototype aimed for linac mounted, offset detector geometry CBCT systems in radiation therapy, and compared its performance to a conventional one-dimensional ASG (1 DASG). Methods The 2 DASG is an array of 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 1 DASG with a grid ratio of 10, (b) the 2 DASG 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), SNR improvement factor was calculated. Improvement in contrast to noise ratio ( CNR) was demonstrated using a low contrast object. Results In comparison to 1 DASG, 2 DASG reduced SPRs by a factor of 3 to 6 across the range of phantom setups investigated. Ts values for 1D and 2 DASGs were in the range of 21 to 29%, and 5 to 14% respectively. 2 DASG continued to provide lower SPR and Ts at increased air gap and with BT filter. Tp of 1D and 2 DASGs were 70.6% and 84.7% respectively. Due to the septal shadow of the 2 DASG, its pixel specific primary transmission values varied between 32.5% and 99.1%. With respect to 1 DASG, 2 DASG provided up to factor of 1.7 more improvement in SNR across the SPR range investigated. Moreover, 2 DASG provided improved visualization of low contrast objects with respect to 1 DASG and NOASG setups. Conclusions When compared to a conventional 1 DASG, 2 DASG prototype provided noticeably lower SPR and Ts values, indicating its superior scatter suppression performance. 2 DASG 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 2 DASG may potentially translate into more accurate CT numbers and improved contrast resolution in CBCT images. [ABSTRACT FROM AUTHOR]

Background and purpose Ablative radiation therapy can be beneficial for pancreatic cancer, and motion mitigation helps to reduce dose to nearby organs-at-risk. Here, we compared two competing methods of motion mitigation—abdominal compression and respiratory gating. Materials and methods CBCT scans of 19 pancreatic cancer patients receiving stereotactic body radiation therapy were acquired with and without abdominal compression, and 3D target motion was reconstructed from CBCT projection images. Daily target motion without mitigation was compared against motion with compression and with simulated respiratory gating. Gating was free-breathing and based on an external surrogate. Target coverage was also evaluated for each scenario by simulating reduced target margins. Results Without mitigation, average daily target motion in LR/AP/SI directions was 5.3, 7.3, and 13.9 mm, respectively. With abdominal compression, these values were 5.2, 5.3, and 8.5 mm, and with respiratory gating they were 3.2, 3.9, and 5.5 mm, respectively. Reductions with compression were significant in AP/SI directions, while reductions with gating were significant in all directions. Respiratory gating also demonstrated better coverage in the reduced margins scenario. Conclusion Respiratory gating is the most effective strategy for reducing motion in pancreatic SBRT, and may allow for dose escalation through a reduction in target margin. [ABSTRACT FROM AUTHOR]

This work is to analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan–Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ 2 ) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. The fits to the clinic data yield consistent results of large α / β ratios of about 20 Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1 Gy physical dose at isocenters per fraction (⩽5 fractions) to achieve the optimal TCP when compared to the T1 tumors. In conclusion, this systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/ β ratios of about 20 Gy. The six models predict that a BED (calculated with α / β of 20) of 90 Gy is sufficient to achieve TCP ⩾ 95%. Among the models considered, the regrowth model leads to a better fit to the clinical data. [ABSTRACT FROM AUTHOR]

Purpose A primary treatment option for lung cancer patients is surgical resection. Patients who have poor lung function prior to surgery are at increased risk of developing serious and life-threatening complications after surgical resection. Surgeons use nuclear medicine ventilation-perfusion ( VQ) scans along with pulmonary function test ( PFT) information to assess a patient's pre-surgical lung function. The nuclear medicine images and pre-surgery PFTs are used to calculate percent predicted postoperative (% PPO) PFT values by estimating the amount of functioning lung tissue that would be lost with surgical resection. Nuclear medicine imaging is currently considered the standard of care when evaluating the amount of ventilation that would be lost due to surgery. A novel lung function imaging modality has been developed in radiation oncology that uses 4-Dimensional computed tomography data to calculate ventilation maps (4 DCT-ventilation). Compared to nuclear medicine, 4 DCT-ventilation is cheaper, does not require a radioactive contrast agent, provides a faster imaging procedure, and has improved spatial resolution. In this work we perform a retrospective study to assess the use of 4 DCT-ventilation as a pre-operative surgical lung function evaluation tool. Specifically, the purpose of our study was to compare % PPO PFT values calculated with 4 DCT-ventilation and % PPO PFT values calculated with nuclear medicine ventilation-perfusion imaging. Methods The study included 16 lung cancer patients that had undergone 4 DCT imaging, nuclear medicine imaging, and had Forced Expiratory Volume in 1 second ( FEV1) acquired as part of a standard PFT. The 4 DCT datasets, spatial registration, and a density-change-based model were used to compute 4 DCT-ventilation maps. Both 4 DCT-ventilation and nuclear medicine images were used to calculate % PPO FEV1. The % PPO FEV1 was calculated by scaling the pre-surgical FEV1 by (1-fraction of total resected ventilation); where the resected ventilation was determined using either the 4 DCT-ventilation or nuclear medicine imaging. Calculations were done assuming both lobectomy and pneumonectomy resections. The % PPO FEV1 values were compared between the 4 DCT-ventilation-based calculations and the nuclear medicine-based calculations using correlation coefficients, average differences, and Receiver Operating Characteristic ( ROC) analysis. Results Overall the 4 DCT-ventilation derived % PPO FEV1 values agreed well with nuclear medicine-derived % PPO FEV1 data with correlations of 0.99 and 0.81 for lobectomy and pneumonectomy, respectively. The average differences between the 4 DCT-ventilation and nuclear medicine-based calculation for % PPO FEV1 were less than 5%. ROC analysis revealed predictive accuracy that ranged from 87.5% to 100% when assessing the ability of 4 DCT-ventilation to predict for nuclear medicine-based % PPO FEV1 values. Conclusions 4 DCT-ventilation is an innovative technology developed in radiation oncology that has great potential to translate to the surgical domain. The high correlation results when comparing 4 DCT-ventilation to the current standard of care provide a strong rationale for a prospective clinical trial assessing 4 DCT-ventilation in the clinical setting. 4 DCT-ventilation can reduce the cost and imaging time for patients while providing improved spatial accuracy and quantitative results for surgeons. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax.Methods and Materials: Published studies on lung toxicity in patients with early-stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT.Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT.Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk. [ABSTRACT FROM AUTHOR]

Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer.Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change-based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung.Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions.Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach. [ABSTRACT FROM AUTHOR]