Impact of abdominal compression on heart and stomach motion for stereotactic arrhythmia radioablation.

PURPOSE: To evaluate the effectiveness of abdominal compression (AC) as a respiratory motion management method for the heart and stomach during stereotactic arrhythmia radioablation (STAR). METHODS: 4D computed tomography (4DCT) scans of patients imaged with AC or without AC (free-breathing: FB) were obtained from ventricular-tachycardia (VT) (n = 3), lung cancer (n = 18), and liver cancer (n = 18) patients. Patients treated for VT were imaged both FB and with AC. Lung and liver patients were imaged once with FB or with AC, respectively. The heart, left ventricle (LV), LV components (LVCs), and stomach were contoured on each phase of the 4DCTs. Centre of mass (COM) translations in the left/right (LR), ant/post (AP), and sup/inf (SI) directions were measured for each structure. Minimum distances between LVCs and the stomach over the respiratory cycle were also measured on each 4DCT phase. Mann-Whitney U-tests were performed between AC and FB datasets with a significance of α = 0.05. RESULTS: No statistical difference (all p values were >0.05) was found in COM translations between FB and AC patient datasets for all contoured cardiac structures. A reduction in COM translation with AC relative to FB was patient, direction, and structure specific for the three VT patients. A significant decrease in the AP range of motion of the stomach was observed under AC compared to FB. No statistical difference was found between minimum distances to the stomach and LVCs between FB and AC. CONCLUSIONS: AC was not a consistent motion management method for STAR, nor does not uniformly affect the separation distance between LVCs and the stomach. If AC is employed in future STAR protocols, the motion of the target volume and its relative distance to the stomach should be compared on two 4DCTs: one while the patient is FB and one under AC.

A high-throughput alpha particle irradiation system for monitoring DNA damage repair, genome instability and screening in human cell and yeast model systems.

Ionizing radiation (IR) is environmentally prevalent and, depending on dose and linear energy transfer (LET), can elicit serious health effects by damaging DNA. Relative to low LET photon radiation (X-rays, gamma rays), higher LET particle radiation produces more disease causing, complex DNA damage that is substantially more challenging to resolve quickly or accurately. Despite the majority of human lifetime IR exposure involving long-term, repetitive, low doses of high LET alpha particles (e.g. radon gas inhalation), technological limitations to deliver alpha particles in the laboratory conveniently, repeatedly, over a prolonged period, in low doses and in an affordable, high-throughput manner have constrained DNA damage and repair research on this topic. To resolve this, we developed an inexpensive, high capacity, 96-well plate-compatible alpha particle irradiator capable of delivering adjustable, low mGy/s particle radiation doses in multiple model systems and on the benchtop of a standard laboratory. The system enables monitoring alpha particle effects on DNA damage repair and signalling, genome stability pathways, oxidative stress, cell cycle phase distribution, cell viability and clonogenic survival using numerous microscopy-based and physical techniques. Most importantly, this method is foundational for high-throughput genetic screening and small molecule testing in mammalian and yeast cells.

Structure guided deformable image registration for treatment planning CT and post stereotactic body radiation therapy (SBRT) Primovist® (Gd-EOB-DTPA) enhanced MRI.

The purpose of this study was to assess the performance of structure-guided deformable image registration (SG-DIR) relative to rigid registration and DIR using TG-132 recommendations. This assessment was performed for image registration of treatment planning computed tomography (CT) and magnetic resonance imaging (MRI) scans with Primovist® contrast agent acquired post stereotactic body radiation therapy (SBRT). SBRT treatment planning CT scans and posttreatment Primovist® MRI scans were obtained for 14 patients. The liver was delineated on both sets of images and matching anatomical landmarks were chosen by a radiation oncologist. Rigid registration, DIR, and two types of SG-DIR (using liver contours only; and using liver structures along with anatomical landmarks) were performed for each set of scans. TG-132 recommended metrics were estimated which included Dice Similarity Coefficient (DSC), Mean Distance to Agreement (MDA), Target Registration Error (TRE), and Jacobian determinant. Statistical analysis was performed using Wilcoxon Signed Rank test. The median (range) DSC for rigid registration was 0.88 (0.77-0.89), 0.89 (0.81-0.93) for DIR, and 0.90 (0.86-0.94) for both types of SG-DIR tested in this study. The median MDA was 4.8 mm (3.7-6.8 mm) for rigid registration, 3.4 mm (2.4-8.7 mm) for DIR, 3.2 mm (2.0-5.2 mm) for SG-DIR where liver structures were used to guide the registration, and 2.8 mm (2.1-4.2 mm) for the SG-DIR where liver structures and anatomical landmarks were used to guide the registration. The median TRE for rigid registration was 7.2 mm (0.5-23 mm), 6.8 mm (0.7-30.7 mm) for DIR, 6.1 mm (1.1-20.5 mm) for the SG-DIR guided by only the liver structures, and 4.1 mm (0.8-19.7 mm) for SG-DIR guided by liver contours and anatomical landmarks. The SG-DIR shows higher liver conformality as per TG-132 metrics and lowest TRE compared to rigid registration and DIR in Velocity AI software for the purpose of registering treatment planning CT and post-SBRT MRI for the liver region. It was found that TRE decreases when liver contours and corresponding anatomical landmarks guide SG-DIR.

Development and clinical implementation of eclipse scripting-based automated patient-specific collision avoidance software.

PURPOSE: Increased use of Linac-based stereotactic radiosurgery (SRS), which requires highly noncoplanar gantry trajectories, necessitates the development of efficient and accurate methods of collision detection during the treatment planning process. This work outlines the development and clinical implementation of a patient-specific computed tomography (CT) contour-based solution that utilizes Eclipse Scripting to ensure maximum integration with clinical workflow. METHODS: The collision detection application uses triangle mesh structures of the gantry and couch, in addition to the body contour of the patient taken during CT simulation, to virtually simulate patient treatments. Collision detection is performed using Binary Tree Hierarchy detection methods. Algorithm accuracy was first validated for simple cuboidal geometry using a calibration phantom and then extended to an anthropomorphic phantom simulation by comparing the measured minimum distance between structures to the predicted minimum distance for all allowable orientations. The collision space was tested at couch angles every 15° from 90 to 270 with the gantry incremented by 5° through the maximum trajectory. Receiver operating characteristic curve analysis was used to assess algorithm sensitivity and accuracy for predicting collision events. Following extensive validation, the application was implemented clinically for all SRS patients. RESULTS: The application was able to predict minimum distances between structures to within 3 cm. A safety margin of 1.5 cm was sufficient to achieve 100% sensitivity for all test cases. Accuracy obtained was 94.2% with the 5 cm clinical safety margin with 100% true positive collision detection. A total of 88 noncoplanar SRS patients have been currently tested using the application with one collision detected and no undetected collisions occurring. The average time for collision testing per patient was 2 min 58 s. CONCLUSIONS: A collision detection application utilizing patient CT contours was developed and successfully clinically implemented. This application allows collisions to be detected early during the planning process, avoiding patient delays and unnecessary resource utilization if detected during delivery.

Stereotactic Optimized Automated Radiotherapy (SOAR): a novel automated planning solution for multi-metastatic SRS compared to HyperArc™.

Objective.Automated Stereotactic Radiosurgery (SRS) planning solutions improve clinical efficiency and reduce treatment plan variability. Available commercial solutions employ a template-based strategy that may not be optimal for all SRS patients. This study compares a novel beam angle optimized Volumetric Modulated Arc Therapy (VMAT) planning solution for multi-metastatic SRS to the commercial solution HyperArc.Approach.Stereotactic Optimized Automated Radiotherapy (SOAR) performs automated plan creation by combining collision prediction, beam angle optimization, and dose optimization to produce individualized high-quality SRS plans using Eclipse Scripting. In this retrospective study 50 patients were planned using SOAR and HyperArc. Assessed dose metrics included the Conformity Index (CI), Gradient Index (GI), and doses to organs-at-risk. Complexity metrics evaluated the modulation, gantry speed, and dose rate complexity. Plan dosimetric quality, and complexity were compared using double-sided Wilcoxon signed rank tests (α= 0.05) adjusted for multiple comparisons.Main Results.The median target CI was 0.82 with SOAR and 0.79 with HyperArc (p < .001). Median GI was 1.85 for SOAR and 1.68 for HyperArc (p < .001). The median V12Gy normal brain volume for SOAR and HyperArc were 7.76 cm3and 7.47 cm3respectively. Median doses to the eyes, lens, optic nerves, and optic chiasm were statistically significant favoring SOAR. The SOAR algorithm scored lower for all complexity metrics assessed.Significance.In-house developed automated planning solutions are a viable alternative to commercial solutions. SOAR designs high-quality patient-specific SRS plans with a greater degree of versatility than template-based methods.

Can machine learning models improve early detection of brain metastases using diffusion weighted imaging-based radiomics?

Background: Metastatic complications are a major cause of cancer-related morbidity, with up to 40% of cancer patients experiencing at least one brain metastasis. Earlier detection may significantly improve patient outcomes and overall survival. We investigated machine learning (ML) models for early detection of brain metastases based on diffusion weighted imaging (DWI) radiomics. Methods: Longitudinal diffusion imaging from 116 patients previously treated with stereotactic radiosurgery (SRS) for brain metastases were retrospectively analyzed. Clinical contours from 600 metastases were extracted from radiosurgery planning computed tomography, and rigidly registered to corresponding contrast enhanced-T1 and apparent diffusion coefficient (ADC) maps. Contralateral contours located in healthy brain tissue were used as control. The dataset consisted of (I) radiomic features using ADC maps, (II) radiomic feature change calculated using timepoints before the metastasis manifested on contrast enhanced-T1, (III) primary cancer, and (IV) anatomical location. The dataset was divided into training and internal validation sets using an 80/20 split with stratification. Four classification algorithms [Linear Support Vector Machine (SVM), Random Forest (RF), AdaBoost, and XGBoost] underwent supervised classification training, with contours labeled either 'control' or 'metastasis'. Hyperparameters were optimized towards balanced accuracy. Various model metrics (receiver operating characteristic curve area scores, accuracy, recall, and precision) were calculated to gauge performance. Results: The radiomic and clinical data set, feature engineering, and ML models developed were able to identify metastases with an accuracy of up to 87.7% on the training set, and 85.8% on an unseen test set. XGBoost and RF showed superior accuracy (XGBoost: 0.877±0.021 and 0.833±0.47, RF: 0.823±0.024 and 0.858±0.045) for training and validation sets, respectively. XGBoost and RF also showed strong area under the receiver operating characteristic curve (AUC) performance on the validation set (0.910±0.037 and 0.922±0.034, respectively). AdaBoost performed slightly lower in all metrics. SVM model generalized poorly with the internal validation set. Important features involved changes in radiomics months before manifesting on contrast enhanced-T1. Conclusions: The proposed models using diffusion-based radiomics showed encouraging results in differentiating healthy brain tissue from metastases using clinical imaging data. These findings suggest that longitudinal diffusion imaging and ML may help improve patient care through earlier diagnosis and increased patient monitoring/follow-up. Future work aims to improve model classification metrics, robustness, user-interface, and clinical applicability.

Fast stereotactic radiosurgery planning using patient-specific beam angle optimization and automation.

BACKGROUND AND PURPOSE: Linac-based stereotactic radiosurgery (SRS) planning for multi-metastatic cases is a complex and intensive process. A manual planning strategy starts with a template-based set of beam angles and applies modifications though a trial and error process. Beam angle optimization uses patient specific geometric heuristics to determine beam angles that provide optimal target coverage and avoid treating through Organs-at-Risk (OARs). This study expands on a collision prediction application developed using an application programming interface, integrating beam angle optimization and collision prediction into a Stereotactic Optimized Automated Radiotherapy (SOAR) planning algorithm. MATERIALS AND METHODS: Twenty-five patient plans, previously treated with SRS for multi-metastatic intracranial tumors, were selected for a retrospective plan study comparing the manual planning strategy to SOAR. The SOAR algorithm was used to select isocenters, table, collimator, and gantry angles, and target groupings for the optimized plans. Dose-volume metrics for relevant OARs and PTVs were compared using double-sided Wilcoxon signed rank tests (α = 0.05). A subset of five patients were included in an efficiency study comparing manual planning times to SOAR automated times. RESULTS: OAR dose metrics compared between planning strategies showed no statistical difference for the dataset of twenty-five plans. Differences in maximum PTV dose and the conformity index were improved for SOAR planning and statistically significant. The median SOAR planning time was 9.8 min compared to 55 min for the manual planning strategy. CONCLUSIONS: SOAR planning was comparable in plan quality to a manual planning strategy with the possibility for greatly improving planning efficiency through automation.

Auto-delineation framework for the focal liver reaction observed in post Stereotactic Body Radiation Therapy (SBRT) Primovist MRI scans.

Development of a novel auto-delineation methodology for observed hypointensity from focal liver reaction in hepatobiliary-specific contrast (Primovist) enhanced MRI acquired post Stereotactic Body Radiation Therapy (SBRT). Additionally, the methodology for the quantification of the threshold dose associated with the observed focal liver reaction was also established. An auto-delineation algorithm was created based on the correlation between intensity and radiation dose information. The error associated with the auto-delineation was quantified using virtual FLRs, as well as clinical patient scans. Patients underwent liver SBRT with a total dose prescription of 50 Gy in 5 fractions. An inherent correlation was established between the contrast-to-noise ratio (CNR) on MRI scans and expected performance of the algorithm using centre-of-mass (COM). Threshold dose associated with focal liver reaction was quantified for all ten patients and verified with associated most conformal isodose line. Based on the CNR vs COM error relationship, the expected median (range) auto-delineation COM error for ten patients was 0.5 (0 to 3.2) mm. The median threshold dose for ten clinical cases was 21.3 Gy based on the auto-delineation framework. This threshold dose was compared to the most conformal isodose line with the hypointensity; there was no significant difference observed (p = 0.6). We developed a framework for post-SBRT Primovist observed focal liver reaction localization. Furthermore, this study established an automated approach for the determination of the threshold dose associated with the hypointense region.

High replication stress and limited Rad51-mediated DNA repair capacity, but not oxidative stress, underlie oligodendrocyte precursor cell radiosensitivity.

Cranial irradiation is part of the standard of care for treating pediatric brain tumors. However, ionizing radiation can trigger serious long-term neurologic sequelae, including oligodendrocyte and brain white matter loss enabling neurocognitive decline in children surviving brain cancer. Oxidative stress-mediated oligodendrocyte precursor cell (OPC) radiosensitivity has been proposed as a possible explanation for this. Here, however, we demonstrate that antioxidants fail to improve OPC viability after irradiation, despite suppressing oxidative stress, suggesting an alternative etiology for OPC radiosensitivity. Using systematic approaches, we find that OPCs have higher irradiation-induced and endogenous γH2AX foci compared to neural stem cells, neurons, astrocytes and mature oligodendrocytes, and these correlate with replication-associated DNA double strand breakage. Furthermore, OPCs are reliant upon ATR kinase and Mre11 nuclease-dependent processes for viability, are more sensitive to drugs increasing replication fork collapse, and display synthetic lethality with PARP inhibitors after irradiation. This suggests an insufficiency for homology-mediated DNA repair in OPCs-a model that is supported by evidence of normal RPA but reduced RAD51 filament formation at resected lesions in irradiated OPCs. We therefore propose a DNA repair-centric mechanism of OPC radiosensitivity, involving chronically-elevated replication stress combined with 'bottlenecks' in RAD51-dependent DNA repair that together reduce radiation resilience.

Position-probability-sampled Monte Carlo calculation of VMAT, 3DCRT, step-shoot IMRT, and helical tomotherapy dose distributions using BEAMnrc/DOSXYZnrc.

PURPOSE: The commercial release of volumetric modulated arc therapy techniques using a conventional linear accelerator and the growing number of helical tomotherapy users have triggered renewed interest in dose verification methods, and also in tools for exploring the impact of machine tolerance and patient motion on dose distributions without the need to approximate time-varying parameters such as gantry position, MLC leaf motion, or patient motion. To this end we have developed a Monte Carlo-based calculation method capable of simulating a wide variety of treatment techniques without the need to resort to discretization approximations. METHODS: The ability to perform complete position-probability-sampled Monte Carlo dose calculations was implemented in the BEAMnrc/DOSXZYnrc user codes of EGSnrc. The method includes full accelerator head simulations of our tomotherapy and Elekta linacs, and a realistic representation of continous motion via the sampling of a time variable. The functionality of this algorithm was tested via comparisons with both measurements and treatment planning dose distributions for four types of treatment techniques: 3D conformal, step-shoot intensity modulated radiation therapy, helical tomotherapy, and volumetric modulated are therapy. RESULTS: For static fields, the absolute dose agreement between the EGSnrc Monte Carlo calculations and measurements is within 2%/1 mm. Absolute dose agreement between Monte Carlo calculations and treatment planning system for the four different treatment techniques is within 3%/3 mm. Discrepancies with the tomotherapy TPS on the order of 10%/5 mm were observed for the extreme example of a small target located 15 cm off-axis and planned with a low modulation factor. The increase in simulation time associated with using position-probability sampling, as opposed to the discretization approach, was less than 2% in most cases. CONCLUSIONS: A single Monte Carlo simulation method can be used to calculate patient dose distribution for various types of treatment techniques delivered with either tomotherapy or a conventional linac. The method simplifies the simulation process, improves dose calculation accuracy, and involves an acceptably small change in computation time.

Investigating diffusion patterns of brain metastases pre- and post-stereotactic radiosurgery: a feasibility study.

Purpose.Metastatic complications are responsible for 90% of cancer-associated mortality. Magnetic resonance imaging (MRI) can be used to observe the brain's microstructure and potentially correlate changes with metastasis occurrence. Diffusion weighted imaging (DWI) is an MRI technique that utilizes the kinetics of water molecules within the body. The aim of this study is to use DWI to characterize diffusion changes within brain metastases in cancer patients pre- and post-stereotactic radiosurgery (SRS).Methods.We retrospectively analyzed 113 metastases from 13 patients who underwent SRS for brain metastasis recurrence. Longitudinal apparent diffusion coefficient (ADC) maps were registered to Gd-T1 images and CT, and clinical metastasis ROIs from all SRS treatments were retrospectively transferred onto these ADC maps for analysis. Metastases were characterized based on pre-SRS diffusion pattern, primary cancer site, and post-SRS outcome. ADC values were calculated pre- and post-SRS.Results.ADC values were significantly elevated (980.2 × 10-6mm2s-1and 1040.3 × 10-6mm2s-1pre- and post-SRS, respectively) when compared to healthy brain tissue (826.8 × 10-6mm2s-1) for all metastases. Three identified pre-SRS patterns were significantly different before SRS and within 6 months post-SRS. No significant differences were observed between different primaries pre-SRS. Post-SRS, Lung metastases ADC decreased by 86.2 × 10-6mm2s-1, breast metastases increased by 116.7 × 10-6mm2s-1, and genitourinary metastases showed no significant ADC change. SRS outcomes showed ADC variability pre-treatment but no significant differences pre- and post-SRS, except at 6-9 months post-SRS where progressing metastases were elevated when compared to other response groups.Conclusion. This study provided a unique opportunity to characterize diffusion changes in brain metastases before their manifestation on standard Gd-T1 images and post-SRS. Identified patterns may improve early detection of brain metastases as well as predict their response to treatment.

Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias.

Cardiac tachyarrhythmias are a major cause of morbidity and mortality. Treatments for these tachyarrhythmias include antiarrhythmic drugs, catheter ablation, surgical ablation, cardiac implantable electronic devices, and cardiac transplantation. Each of these treatment approaches is effective in some patients but there is considerable room for improvement, particularly with respect to the most common of the tachydysrhythmias, atrial fibrillation, and the most dangerous of the tachydysrhythmias, ventricular tachycardia (VT) or ventricular fibrillation. Noninvasive stereotactic ablative radiation therapy is emerging as an effective treatment for refractory tachyarrhythmias. Animal models have shown successful ablation of arrhythmogenic myocardial substrates with minimal short-term complications. Studies of stereotactic radioablation involving patients with refractory VT have shown a reduction in VT recurrence and promising early safety data. In this review, we provide the background for the application of stereotactic arrhythmia radioablation therapy along with promising results from early applications of the technology.

Les tachyarythmies cardiaques sont une cause importante de morbidité et de mortalité. Les traitements employés comprennent des antiarythmiques, l'ablation par cathéter, l'ablation par chirurgie, l'implantation de dispositifs cardiaques électroniques et la transplantation cardiaque. Toutes ces démarches thérapeutiques sont efficaces dans certains cas, mais les traitements peuvent encore être largement améliorés, en particulier en ce qui concerne la fibrillation auriculaire, qui est la tachyarythmie la plus fréquente, et la tachycardie ventriculaire (TV, aussi appelée fibrillation ventriculaire), qui est la tachyarythmie la plus dangereuse. La radiochirurgie stéréotaxique non invasive se démarque de plus en plus comme traitement efficace des tachyarythmies réfractaires. Des substrats myocardiques arythmogènes ont pu être réséqués avec succès sur des modèles animaux, l'intervention n'ayant entraîné que des complications minimales de courte durée. Dans le cadre d'études menées auprès de patients présentant une TV réfractaire, la radiochirurgie stéréotaxique a permis de réduire le risque de récurrence de la TV, et les premières données sur l'innocuité du traitement sont encourageantes. Dans notre revue, nous précisons le cadre d'application de la radiochirurgie stéréotaxique visant à réséquer le tissu responsable de l'arythmie, et nous présentons les résultats prometteurs des premières applications de la technologie à cette fin.

Dosimetric and radiobiological impact of abdominal compression on adjacent gastro-intestinal critical structures for patients treated with upper and mid-abdominal stereotactic body radiotherapy.

OBJECTIVES: We evaluated the dosimetric and radiobiological impact of abdominal compression (AC) on nearby gastrointestinal critical structures (GI-CS) and reported toxicities of patients treated with non-hepatic abdominal stereotactic body radiotherapy (SBRT). METHODS: Two sets of CT scans, planning scans with AC and pre-treatment diagnostic scans without AC (non-AC) were compared for patients treated with a prescription dose to planning target volume (PTV) ≥25 Gy/5-fractions at a single institution. Target volumes were delineated on both sets of scans and PTV was expanded isotropically by 2 cm (PTV+2) and 4 cm (PTV+4). All GI-CS were summated to create a composite CS (GI-lumen). Rigid registration of AC and non-AC scans was done using Velocity AI (Varian Medical Systems) to obtain dose distribution information. Lymann-Probit and logit models were used for radiobiological calculations. Toxicity scores were obtained from prospectively collected clinical data. RESULTS: A total of 12 patients were included. Mean PTV volumes were 190.3cc and 196.4cc with AC and non-AC (p=0.95). Significant improvement in V30 of GI-lumen was seen with AC (0.11cc vs. 4.97cc, p=0.04). There were no differences in the normal tissue complication probabilities of the individual GI-CS or the summary indices except a notable trend towards better NTCP for small bowel late effects with AC (0.21% vs. 2.45%; p=0.055). Three patients had acute grade-1 anorexia, one patient had acute grade-2 gastritis. There was no grade ≥3 GI toxicity. At a median follow-up of 2.6 years, total of 8/12 (66.7%) patients developed local recurrence of whom 4 (33.3%) had isolated local recurrence. CONCLUSION: Use of AC did not result in any dosimetric or radiobiological inferiority for GI-CS. The current cohort completed their treatment with minimal toxicity.

The cost of radiation therapy.

BACKGROUND AND PURPOSE: The rising cost of health care is of universal concern. If the cost effectiveness of conventional and novel radiotherapeutic strategies is to be established we need to have confidence in our estimates of both cost and effectiveness. The purpose of this study is to explore the degree of consistency of recently published cost estimates for radiation therapy. METHODS AND MATERIALS: Eleven publications form the basis of this analysis. From each study we have estimated the cost of a 21 fraction course (when possible) of radiation therapy. The costs have been decomposed into the three inputs: process, clinical infrastructure and supporting infrastructure. We have also investigated the time course of radiation therapy costs over the last two decades. RESULTS: From the latest four studies we conclude that the cost of a 21 fraction course of radiation therapy is 3239 euro+/-566 euro. The percentages of this total spent on process, clinical infrastructure and supporting infrastructure over the last 15 years are 54, 29 and 17, respectively. The real increase in the cost of radiotherapy over the last 15 years is estimated to be approximately 5.5%. CONCLUSION: Cost estimates for radiation therapy appear to be converging. However, we will need far more sophisticated analyses in the future if we are to establish the cost effectiveness of the newer treatment strategies currently under active clinical investigation.

Phantom evaluation of a commercially available three modality image guided radiation therapy system.

The authors describe a detailed evaluation of the capabilities of imaging and image registration systems available with Varian linear accelerators for image guided radiation therapy (IGRT). Specifically, they present modulation transfer function curves for megavoltage planar, kilovoltage (kV) planar, and cone beam computed tomography imaging systems and compare these with conventional computed tomography. While kV planar imaging displayed the highest spatial resolution, all IGRT imaging techniques were assessed as adequate for their intended purpose. They have also characterized the image registration software available for use in conjunction with these imaging systems through a comprehensive phantom study involving translations in three orthogonal directions. All combinations of imaging systems and image registration software were found to be accurate, although the planar kV imaging system with automatic registration was generally superior, with both accuracy and precision of the order of 1 mm, under the conditions tested. Based on their phantom study, the attainable accuracy for rigid body translations using any of the features available with Varian equipment will more likely be limited by the resolution of the couch readouts than by inherent limitations in the imaging systems and image registration software. Overall, the accuracy and precision of currently available IGRT technology exceed published experience with the accuracy and precision of contouring for planning.

Evaluation of linear accelerator performance standards using an outcome oriented approach.

Radiation therapy, along with other branches of medicine, is moving towards a firmer basis in evidence to optimally utilize resources. As new treatment technology and strategies place greater demands on quality assurance resources, the need to objectively evaluate equipment and process performance standards from the perspective of predicted clinical impact becomes more urgent. This study evaluates the appropriateness of recommended quality control tolerance and action levels for linear accelerators based on the calculated dosimetric impact of suboptimal equipment performance. A method is described to quantify the dosimetric changes, as reflected by the changes in the outcome surrogate, equivalent uniform dose (EUD), of machine performance deviations from the optimal, specifically in the range of tolerance and action levels promulgated by the Canadian Association of Provincial Cancer Agencies (CAPCA). Linear accelerator performance deviations were simulated for the treatment of prostate, breast, lung, and brain using 3D conformal techniques, and the impact evaluated in terms of the changes in the EUD of the target volumes and two principal organs at risk (OARs) per site. The eight key performance characteristics examined are: Output constancy, beam flatness, gantry angle, collimator angle, field size indicator, laser alignment (three directions) and, by inference, the optical distance indicator. Currently accepted CAPCA tolerance levels for these eight performance characteristics are shown to maintain average EUD deviations to within 2% for the targets and 2 Gy for the OARs. However, within the 2% or 2 Gy range, the recommended tolerance levels are found to have markedly different effects on the EUDs of the structures of interest.

The Equivalent Uniform Dose as a severity metric for radiation treatment incidents.

In allocating resources within a risk management program, ideally we would like to know both the probabilities and consequences of potential incidents. We simulate, on a treatment planning computer, several commonly reported incidents in radiation treatment and explore their consequences for the EUDs of targets and organs at risk.

Technical Note: A novel quality assurance test to identify gantry angle inaccuracies in respiratory-gated VMAT treatments.

PURPOSE: During respiratory-gated volumetric-modulated arc therapy (VMAT), the radiation beam is turned off each time the target exits the gating window. At the same time, the gantry slows, stops, and rewinds before the beam is turned back on. A quality assurance (QA) test was developed to detect inaccuracies in the gantry angle position between beam-off and beam-on events during respiratory-gated VMAT. METHODS: Strips of Gafchromic™ EBT3 film were taped to the surface of a Capthan® 504 phantom mounted at isocenter. A homogeneous dose was delivered to the films through a 2 cm × 10 cm slit in the jaws using a respiratory-gated VMAT arc without the multileaf collimator. A periodic breathing cycle was used. Errors in gated delivery ranging from 0.5 to 5° were simulated by delivering nongated arcs with the same field size with over- and underlapping sections of 0.5-5°. The simulated errors were used to define QA levels to analyze the gated delivery. RESULTS: The QA test was capable of detecting errors as small as 0.5°. The test was delivered to three Varian TrueBeam™ linacs, and no gantry angle inaccuracies greater than or equal to 0.5° were detected on any of the films. CONCLUSIONS: A QA test capable of detecting gantry angle inaccuracies at beam-off and subsequent beam-on as small as 0.5° was developed and implemented for Varian TrueBeam™ linacs.

A comparison of techniques for simulating set-up error and uncertainty in head and neck IMRT.

We have compared four computational methods for quantifying the effect of set-up error and uncertainty on delivered doses to targets and organs at risk in the intensity modulated radiation therapy treatment of head and neck cancer. These four methods were direct simulation, simple convolution, plus two modified convolution approaches. Discrepancies of up to 20% in the equivalent uniform dose (EUD) between direct simulation and simple convolution were estimated for the relatively superficial parotid gland at a systematic set-up error of 6 mm standard deviation and a random uncertainty of 2 mm standard deviation. Truncated convolution agreed with direct simulation to within 6% for all situations studied. However, of the four methods, only direct simulation can quantify the range of outcomes (EUD) associated with a finite number of courses and fractions. Our results are particularly relevant to the design of dose escalation studies in head and neck cancer.

Intensity modulated radiation therapy for oropharyngeal cancer: the sensitivity of plan objectives and constraints to set-up uncertainty.

The goal of this study was to assess the impact of set-up uncertainty on compliance with the objectives and constraints of an intensity modulated radiation therapy protocol for early stage cancer of the oropharynx. As the convolution approach to the quantitative study of set-up uncertainties cannot accommodate either surface contours or internal inhomogeneities, both of which are highly relevant to sites in the head and neck, we have employed the more resource intensive direct simulation method. The impact of both systematic (variable from 0 to 6 mm) and random (fixed at 2 mm) set-up uncertainties on compliance with the criteria of the RTOG H-0022 protocol has been examined for eight geometrically complex structures: CTV66 (gross tumour volume and palpable lymph nodes suspicious for metastases), CTV54 (lymph node groups or surgical neck levels at risk of subclinical metastases), glottic larynx, spinal cord, brainstem, mandible and left and right parotids. In a probability-based approach, both dose-volume histograms and equivalent uniform doses were used to describe the dose distributions achieved by plans for two patients, in the presence of set-up uncertainty. The equivalent uniform dose is defined to be that dose which, when delivered uniformly to the organ of interest, will lead to the same response as the non-uniform dose under consideration. For systematic set-up uncertainties greater than 2 mm and 5 mm respectively, coverage of the CTV66 and CTV54 could be significantly compromised. Directional sensitivity was observed in both cases. Most organs at risk (except the glottic larynx which did not comply under static conditions) continued to meet the dose constraints up to 4 mm systematic uncertainty for both plans. The exception was the contra lateral parotid gland, which this protocol is specifically designed to protect. Sensitivity to systematic set-up uncertainty of 2 mm was observed for this organ at risk in both clinical plans.