Preclinical Ultra-High Dose Rate (FLASH) Proton Radiation Therapy System for Small Animal Studies.

Purpose: Animal studies with ultrahigh dose-rate radiation therapy (FLASH, >40 Gy/s) preferentially spare normal tissues without sacrificing antitumor efficacy compared with conventional dose-rate radiation therapy (CONV). At the University of Washington, we developed a cyclotron-generated preclinical scattered proton beam with FLASH dose rates. We present the technical details of our FLASH radiation system and preliminary biologic results from whole pelvis radiation. Methods and Materials: A Scanditronix MC50 compact cyclotron beamline has been modified to produce a 48.7 MeV proton beam at dose rates between 0.1 and 150 Gy/s. The system produces a 6 cm diameter scattered proton beam (flat to ± 3%) at the target location. Female C57BL/6 mice 5 to 6 weeks old were used for all experiments. To study normal tissue effects in the distal colon, mice were irradiated using the entrance region of the proton beam to the whole pelvis, 18.5 Gy at different dose rates: control, CONV (0.6-1 Gy/s) and FLASH (50-80 Gy/s). Survival was monitored daily and EdU (5-ethynyl-2´-deoxyuridine) staining was performed at 24- and 96-hours postradiation. Cleaved caspase-3 staining was performed 24-hours postradiation. To study tumor control, allograft B16F10 tumors were implanted in the right flank and received 18 Gy CONV or FLASH proton radiation. Tumor growth and survival were monitored. Results: After 18.5 Gy whole pelvis radiation, survival was 100% in the control group, 0% in the CONV group, and 44% in the FLASH group (P < .01). EdU staining showed cell proliferation was significantly higher in the FLASH versus CONV group at both 24-hours and 96-hours postradiation in the distal colon, although both radiation groups showed decreased proliferation compared with controls (P < .05). Lower cleaved caspase-3 staining was seen in the FLASH versus conventional group postradiation (P < .05). Comparable flank tumor control was observed in the CONV and FLASH groups. Conclusions: We present our preclinical FLASH proton radiation system and biologic results showing improved survival after whole pelvis radiation, with equivalent tumor control.

Simulation-guided development of an optical calorimeter for high dose rate dosimetry.

Optical Calorimetry (OC) is based on interferometry and provides a direct measurement of spatially resolved absorbed dose to water by measuring refractive index changes induced by radiation. The purpose of this work was to optimize and characterize in software an OC system tailored for ultra-high dose rate applications and to build and test a prototype in a clinical environment. A radiation dosimeter using the principles of OC was designed in optical modelling software. Traditional image quality instruments, fencepost and contrast phantoms, were utilized both in software and experimentally in a lab environment to investigate noise reduction techniques and to test the spatial and dose resolution of the system. Absolute dose uncertainty was assessed by measurements in a clinical 6 MV Flattening Filter Free (FFF) photon beam with dose rates in the range 0.2-6 Gy/s achieved via changing the distance from the source. Design improvements included: equalizing the pathlengths of the interferometer, isolating the system from external vibrations and controlling the system's internal temperature as well as application of mathematical noise reduction techniques. Simulations showed that these improvements should increase the spatial resolution from 22 to 35 lp/mm and achieve a minimum detectable dose of 0.2 Gy, which was confirmed experimentally. In the FFF beam, the absolute dose uncertainty was dose rate dependent and decreased from 2.5 ± 0.8 to 2.5 ± 0.2 Gy for dose rates of 0.2 and 6 Gy/s, respectively. A radiation dosimeter utilizing the principles of OC was developed and constructed. Optical modelling software and image quality phantoms allowed for iterative testing and refinement. The refined OC system proved capable of measuring absorbed dose to water in a linac generated photon beam. Reduced uncertainty at higher dose rates indicates the potential for OC as a dosimetry system for high dose rate techniques such as microbeam and ultra-high dose-rate radiotherapy.

Framework for Radiation Oncology Department-wide Evaluation and Implementation of Commercial Artificial Intelligence Autocontouring.

PURPOSE: Artificial intelligence (AI)-based autocontouring in radiation oncology has potential benefits such as standardization and time savings. However, commercial AI solutions require careful evaluation before clinical integration. We developed a multidimensional evaluation method to test pretrained AI-based automated contouring solutions across a network of clinics. METHODS AND MATERIALS: Curated data included 121 patient planning computed tomography (CT) scans with a total of 859 clinically approved contours used for treatment from 4 clinics. Regions of interest (ROIs) were generated with 3 commercial AI-based automated contouring software solutions (AI1, AI2, AI3) spanning the following disease sites: brain, head and neck (H&N), thorax, abdomen, and pelvis. Quantitative agreement between AI-generated and clinical contours was measured by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Qualitative assessment was performed by multiple experts scoring blinded AI-contours using a Likert scale. Workflow and usability surveying was also conducted. RESULTS: AI1, AI2, and AI3 contours had high quantitative agreement in 27.8%, 32.8%, and 34.1% of cases (DSC >0.9), performing well in pelvis (median DSC = 0.86/0.88/0.91) and thorax (median DSC = 0.91/0.89/0.91). All 3 solutions had low quantitative agreement in 7.4%, 8.8%, and 6.1% of cases (DSC <0.5), performing worse in brain (median DSC = 0.65/0.78/0.75) and H&N (median DSC = 0.76/0.80/0.81). Qualitatively, AI1 and AI2 contours were acceptable (rated 1-2) with at most minor edits in 70.7% and 74.6% of ROIs (2906 ratings), higher for abdomen (AI1: 79.2%) and thorax (AI2: 90.2%), and lower for H&N (29.0/35.6%). An end-user survey showed strong user preference for full automation and mixed preferences for accuracy versus total number of structures generated. CONCLUSIONS: Our evaluation method provided a comprehensive analysis of both quantitative and qualitative measures of commercially available pretrained AI autocontouring algorithms. The evaluation framework served as a roadmap for clinical integration that aligned with user workflow preference.

Automated planning stage tracking and analysis through an integrated whiteboard system.

PURPOSE: One of the common challenges in delivering complex healthcare procedures such as radiation oncology is the organization and sharing of information in ways that facilitate workflow and prevent treatment delays. Within the major vendors of Oncology Information Systems (OIS) is a lack of tools and displays to assist in task timing and workflow processes. To address this issue, we developed an electronic whiteboard integrated with a local OIS to track, record, and evaluate time frames associated with clinical radiation oncology treatment planning processes. METHODS: We developed software using an R environment hosted on a local web-server at Seattle Cancer Care Alliance (SCCA) in 2017. The planning process was divided into stages, and time-stamped moves between planning stages were recorded automatically via Mosaiq (Elekta, Sweden) Quality Check Lists (QCLs). Whiteboard logs were merged with Mosaiq-extracted diagnostic factors and evaluated for significance. Interventional changes to task time expectations were evaluated for 6 months in 2021 and compared with 6 month periods in 2018 and 2019. RESULTS: Whiteboard/Mosaiq data from the SCCA show that treatment intent, number of prescriptions, and nodal involvement were main factors influencing overall time to plan completion. Contouring and Planning times were improved by 2.6 days (p<10-14) and 2.5 days (p<10-11), respectively. Overall time to plan completion was reduced by 33% (5.1 days; p<10-11). CONCLUSIONS: This report establishes the utility of real-time task tracking tools in a radiotherapy planning process. The whiteboard results provide data-driven evidence to add justification for practice change implementations.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy.

Purpose: We conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and Materials: Patients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. Results: The trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. Conclusions: TraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

A system for equitable workload distribution in clinical medical physics.

BACKGROUND: Clinical medical physics duties include routine tasks, special procedures, and development projects. It can be challenging to distribute the effort equitably across all team members, especially in large clinics or systems where physicists cover multiple sites. The purpose of this work is to study an equitable workload distribution system in radiotherapy physics that addresses the complex and dynamic nature of effort assignment. METHODS: We formed a working group that defined all relevant clinical tasks and estimated the total time spent per task. Estimates used data from the oncology information system, a survey of physicists, and group consensus. We introduced a quantitative workload unit, "equivalent workday" (eWD), as a common unit for effort. The sum of all eWD values adjusted for each physicist's clinical full-time equivalent yields a "normalized total effort" (nTE) metric for each physicist, that is, the fraction of the total effort assigned to that physicist. We implemented this system in clinical operation. During a trial period of 9 months, we made adjustments to include tasks previously unaccounted for and refined the system. The workload distribution of eight physicists over 12 months was compared before and after implementation of the nTE system. RESULTS: Prior to implementation, differences in workload of up to 50% existed between individual physicists (nTE range of 10.0%-15.0%). During the trial period, additional categories were added to account for leave and clinical projects that had previously been assigned informally. In the 1-year period after implementation, the individual workload differences were within 5% (nTE range of 12.3%-12.8%). CONCLUSION: We developed a system to equitably distribute workload and demonstrated improvements in the equity of workload. A quantitative approach to workload distribution improves both transparency and accountability. While the system was motivated by the complexities within an academic medical center, it may be generally applicable for other clinics.

The role of surface-guided radiation therapy for improving patient safety.

Emerging data indicates SGRT could improve safety and quality by preventing errors in its capacity as an independent system in the treatment room. The aim of this work is to investigate the utility of SGRT in the context of safety and quality. Three incident learning systems (ILS) were reviewed to categorize and quantify errors that could have been prevented with SGRT: SAFRON (International Atomic Energy Agency), UW-ILS (University of Washington) and AvIC (Skåne University Hospital). A total of 849/9737 events occurred during the pre-treatment review/verification and treatment stages. Of these, 179 (21%) events were predicted to have been preventable with SGRT. The most common preventable events were wrong isocentre (43%) and incorrect accessories (34%), which appeared at comparable rates among SAFRON and UW-ILS. The proportion of events due to wrong accessories was much smaller in the AvIC ILS, which may be attributable to the mandatory use of SGRT in Sweden. Several case scenarios are presented to demonstrate that SGRT operates as a valuable complement to other quality-improvement tools routinely used in radiotherapy. Cases are noted in which SGRT itself caused incidents. These were mostly related to workflow issues and were of low severity. Severity data indicated that events with the potential to be mitigated by SGRT were of higher severity for all categories except wrong accessories. Improved vendor integration of SGRT systems within the overall workflow could further enhance its clinical utility. SGRT is a valuable tool with the potential to increase patient safety and treatment quality in radiotherapy.

The dosimetric benefit of in-advance respiratory training for deep inspiration breath holding is realized during daily treatment in left breast radiotherapy: A comparative retrospective study of serial surface motion tracking.

INTRODUCTION: A novel approach of in-advance preparatory respiratory training and practice for deep inspiration breath holding (DIBH) has been shown to further reduce cardiac dose in breast cancer radiotherapy patients, enabled by deeper (extended) DIBH. Here we investigated the consistency and stability of such training-induced extended DIBH after training completion and throughout the daily radiotherapy course. METHODS: Daily chestwall motion from real-time surface tracking transponder data was analysed in 67 left breast radiotherapy patients treated in DIBH. Twenty-seven received preparatory DIBH training/practice (prep Trn) 1-2 weeks prior to CT simulation, resulting in an extended DIBH (ext DIBH) and reduced cardiac dose at simulation. Forty had only conventional immediate pre-procedure DIBH instruction without prep Trn and without extended DIBH (non-Trn group). Day-to-day variability in chestwall excursion pattern during radiotherapy was compared among the groups. RESULTS: The average of daily maximum chestwall excursions was overall similar, 2.5 ± 0.6 mm for prep Trn/ext DIBH vs. 2.9 ± 0.8 mm for non-Trn patients (P = 0.24). Chestwall excursions beyond the 3-mm tolerance threshold were less common in the prep Trn/ext DIBH group (18.8% vs. 37.5% of all fractions within the respective groups, P = 0.038). Among patients with cardiopulmonary disease those with prep Trn/ext DIBH had fewer chestwall excursions beyond 3 mm (9.4% vs. 46.7%, P = 0.023) and smaller average maximum excursions than non-Trn patients (2.4 ± 0.3 vs. 3.0 ± 0.6 mm, P = 0.047, respectively). CONCLUSION: Similar stability of daily DIBH among patients with and without preparatory training/practice suggests that the training-induced extended DIBH and cardiac dose reductions were effectively sustained throughout the radiotherapy course. Training further reduced beyond-tolerance chestwall excursions, particularly in patients with cardiopulmonary disease.

Clinical paradigms and challenges in surface guided radiation therapy: Where do we go from here?

Surface guided radiotherapy (SGRT) is becoming a routine tool for patient positioning for specific clinical sites in many clinics. However, it has not yet gained its full potential in terms of widespread adoption. This vision paper first examines some of the difficulties in transitioning to SGRT before exploring the current and future role of SGRT alongside and in concert with other imaging techniques. Finally, future horizons and innovative ideas that may shape and impact the direction of SGRT going forward are reviewed.

Reducing Cardiac Radiation Dose From Breast Cancer Radiation Therapy With Breath Hold Training and Cognitive Behavioral Therapy.

The delivery of radiation therapy shares many of the challenges encountered in imaging procedures. As in imaging, such as MRI, organ motion must be reduced to a minimum, often for lengthy time periods, to effectively target the tumor during imaging-guided therapy while reducing radiation dose to nearby normal tissues. For patients, radiation therapy is frequently a stress- and anxiety-provoking medical procedure, evoking fear from negative perceptions about irradiation, confinement from immobilization devices, claustrophobia, unease with equipment, physical discomfort, and overall cancer fear. Such stress can be a profound challenge for cancer patients' emotional coping and tolerance to treatment, and particularly interferes with advanced radiation therapy procedures where active, complex and repetitive high-level cooperation is often required from the patient.In breast cancer, the most common cancer in women worldwide, radiation therapy is an indispensable component of treatment to improve tumor control and outcome in both breast-conserving therapy for early-stage disease and in advanced-stage patients. High technological complexity and high patient cooperation is required to mitigate the known cardiac toxicity and mortality from breast cancer radiation by reducing the unintended radiation dose to the heart from left breast or left chest wall irradiation. To address this, radiation treatment in daily deep inspiration breath hold (DIBH), to create greater distance between the treatment target and the heart, is increasingly practiced. While holding the promise to decrease cardiac toxicity, DIBH procedures often augment patients' baseline stress and anxiety reaction toward radiation treatment. Patients are often overwhelmed by the physical and mental demands of daily DIBH, including the nonintuitive timed and sustained coordination of abdominal thoracic muscles for prolonged breath holding.While technologies, such as DIBH, have advanced to millimeter-precision in treatment delivery and motion tracking, the "human factor" of patients' ability to cooperate and perform has been addressed much less. Both are needed to optimally deliver advanced radiation therapy with minimized normal tissue effects, while alleviating physical and cognitive distress during this challenging phase of breast cancer therapy.This article discusses physical training and psychotherapeutic integrative health approaches, applied to radiation oncology, to leverage and augment the gains enabled by advanced technology-based high-precision radiation treatment in breast cancer. Such combinations of advanced technologies with training and cognitive integrative health interventions hold the promise to provide simple feasible and low-cost means to improve patient experience, emotional outcomes and quality of life, while optimizing patient performance for advanced imaging-guided treatment procedures - paving the way to improve cardiac outcomes in breast cancer survivors.

Volume effects in the TCP for hypoxic and oxygenated tumors.

PURPOSE: Clinical studies in radiation therapy with conventional fractionation show a reduction in the tumor control probability (TCP) with an increase in the total and hypoxic tumor volumes. The main objective of this article is to derive an analytical relationship between the TCP and the hypoxic and total tumor volumes. This relationship is applied to clinical data on the TCP reduction with increasing total tumor volume and, also, dose escalation to target tumor hypoxia. METHODS: The TCP equation derived from the Poisson probability distribution predicts that both (a) an increase in the number of tumor clonogens and (b) an increase in the average cell surviving fraction are the factors contributing to the loss of local control. Using asymptotic mathematical properties of the TCP formula and the linear quadratic (LQ) cell survival model with two levels of hypoxic and oxygenated cells, we separated the TCP dependence on the total and hypoxic tumor volumes. The predicted trends in the local control as a function of total and hypoxic tumor volumes were evaluated in radiotherapy model problems with conventional dose fractionation for head and neck and non-small cell lung cancers. Tumor-specific parameters in the LQ model and the density of clonogens in the TCP model were taken from published data on predictive assays and the plating efficiency measurements, respectively. RESULTS: Our simulations show that, at the dose levels used in conventional radiation therapy for head and neck and non-small cell lung cancers, the TCP dependence on the total tumor volume is negligible for completely oxygenated tumors. However, the presented results demonstrate that tumor hypoxia introduces a significant volume effect into estimates of the TCP. The extent of tumor hypoxia is a plausible mechanism to explain the TCP reduction with increasing total tumor volume observed in clinical studies. To achieve the same level of tumor control in a hypoxic tumor region relative to well oxygenated tumor regions, the delivered dose should, in principle, be escalated by a factor equal to the oxygen enhancement ratio (OER). The theoretically required hypoxia-targeted dose escalation could be as large as 100% because it has been estimated that hypoxic tumor regions may have an OER = 2 for conventional fractionation. However, our results indicate that clinically acceptable values of the TCP would require much lower hypoxia-targeted dose escalation (<50%) when the effects of total and hypoxic tumor volumes are taken into account. CONCLUSIONS: The reported studies and models suggest that the effect of total tumor volume on the TCP is negligible for oxygenated head and neck and non-small cell lung tumors treated with conventional fractionation. According to our simulations, the volume effects in the TCP observed in clinical studies are defined primarily by the hypoxic volume. This information can be useful for the analysis of treatment outcomes and the dose escalation to target tumor hypoxia.

Characterizing a deformable registration algorithm for surface-guided breast radiotherapy.

PURPOSE: Surface-guided radiation therapy (SGRT) is a nonionizing imaging approach for patient setup guidance, intra-fraction monitoring, and automated breath-hold gating of radiation treatments. SGRT employs the premise that the external patient surface correlates to the internal anatomy, to infer the treatment isocenter position at time of treatment delivery. Deformations and posture variations are known to impact the correlation between external and internal anatomy. However, the degree, magnitude, and algorithm dependence of this impact are not intuitive and currently no methods exist to assess this relationship. The primary aim of this work was to develop a framework to investigate and understand how a commercial optical surface imaging system (C-RAD, Uppsala, Sweden), which uses a nonrigid registration algorithm, handles rotations and surface deformations. METHODS: A workflow consisting of a female torso phantom and software-introduced transformations to the corresponding digital reference surface was developed. To benchmark and validate the approach, known rigid translations and rotations were first applied. Relevant breast radiotherapy deformations related to breast size, hunching/arching back, distended/deflated abdomen, and an irregular surface to mimic a cover sheet over the lower part of the torso were investigated. The difference between rigid and deformed surfaces was evaluated as a function of isocenter location. RESULTS: For all introduced rigid body transformations, C-RAD computed isocenter shifts were determined within 1 mm and 1˚. Additional translational shifts to correct for rotations as a function of isocenter location were determined with the same accuracy. For yaw setup errors, the difference in shift corrections between a plan with an isocenter placed in the center of the breast (BrstIso) and one located 12 cm superiorly (SCFIso) was 2.3 mm/1˚ in lateral direction. Pitch setup errors resulted in a difference of 2.1 mm/1˚ in vertical direction. For some of the deformation scenarios, much larger differences up to 16 mm and 7˚ in the calculated shifts between BrstIso and SCFIso were observed that could lead to large unintended gaps or overlap between adjacent matched fields if uncorrected. CONCLUSIONS: The methodology developed lends itself well for quality assurance (QA) of SGRT systems. The deformable C-RAD algorithm determined accurate shifts for rigid transformations, and this was independent of isocenter location. For surface deformations, the position of the isocenter had considerable impact on the registration result. It is recommended to avoid off-axis isocenters during treatment planning to optimally utilize the capabilities of the deformable image registration algorithm, especially when multiple isocenters are used with fields that share a field edge.

Predictors of cardiac and lung dose sparing in DIBH for left breast treatment.

This retrospective study of left breast radiation therapy (RT) investigates the correlation between anatomical parameters and dose to heart or/and left lung in deep inspiration breath-hold (DIBH) compared to free-breathing (FB) technique. Anatomical parameters of sixty-seven patients, treated with a step-and-shoot technique to 50 Gy or 50.4 Gy were included. They consisted of the cardiac contact distances in axial (CCDax) and parasagittal (CCDps) planes, and the lateral heart-to-chest distance (HCD). Correlation analysis was performed to identify predictors for heart and lung dose sparing. Paired t-test and linear regression were used for data analysis with significance level of p = 0.05. All dose metrics for heart and lung were significantly reduced with DIBH, however 21% of patients analyzed had less than 1.0 Gy mean heart dose reduction. Both FB-CCDpsdistance and FB-HCD correlated with FB mean heart dose and mean DIBH heart dose reduction. The strongest correlation was observed for the ratio of FB-CCDpsand FB-HCD with heart dose sparing. A FB-CCDps and FB-HCD model was developed to predict DIBH induced mean heart dose reduction, with 1.04 Gy per unit of FB-CCDps/FB-HCD. Variation between predicted and actual mean heart dose reduction ranged from -0.6 Gy to 0.6 Gy. In this study, FB-CCDps and FB-HCD distance served as predictors for heart dose reduction with DIBH equally, with FB-CCDps/FB-HCD as a stronger predictor. These parameters and the prediction model could be further investigated for use as a tool to better select patients who will benefit from DIBH.

Accuracy and stability of deep inspiration breath hold in gated breast radiotherapy - A comparison of two tracking and guidance systems.

PURPOSE: To characterize reproducibility of patient breath-hold positioning and compare tracking system performance for Deep Inspiration Breath Hold (DIBH) gated left breast radiotherapy. METHODS: 29 consecutive left breast DIBH patients (655 fractions) were treated under the guidance of Calypso surface beacons with audio-feedback and 35 consecutive patients (631 fractions) were treated using C-RAD Catalyst HD surface imaging with audiovisual feedback. The Calypso system tracks a centroid determined by two radio-frequency transponders, with a manually enforced institutional tolerance, while the surface image based CatalystHD system utilizes real-time biometric feedback to track a pre-selected point with an institutional tolerance enforced by the Elekta Response gating interface. DIBH motion data from Calypso was extracted to obtain the displacement of breath hold marker in ant/post direction from a set-zero reference point. Ant/post point displacement data from CatalystHD was interpreted by computing the difference between raw tracking points and the center of individual gating windows. Mean overall errors were compared using Welsh's unequal variance t-test. Wilcoxon rank sum test were used for statistical analysis with P < 0.05 considered significant. RESULTS: Mean overall error for Calypso and CatalystHD were 0.33 ±â€¯1.17 mm and 0.22 ±â€¯0.43 mm, respectively, with t-test comparison P-value < 0.034. Absolute errors for Calypso and CatalystHD were 0.95 ±â€¯0.75 mm and 0.38 ±â€¯0.30 mm, respectively, with Wilcoxon rank sum test P-value <2×10-16. Average standard deviation per fraction was found to be 0.74 ±â€¯0.44 mm for Calypso patients versus 0.54 ±â€¯0.22 mm for CatalystHD. CONCLUSION: Reduced error distribution widths in overall positioning, deviation of position, and per fraction deviation suggest that the use of functionalities available in CatalystHD such as audiovisual biofeedback and patient surface matching improves accuracy and stability during DIBH gated left breast radiotherapy.

Optical-Radiation-Calorimeter Refinement by Virtual-Sensitivity Analysis.

Digital holographic interferometry (DHI) radiation dosimetry has been proposed as an experimental metrology technique for measuring absorbed radiation doses to water with high spatial resolution via noninvasive optical calorimetry. The process involves digitally recording consecutive interference patterns resulting from variations in the refractive index as a function of the radiation-absorbed dose. Experiments conducted on prototype optical systems revealed the approach to be feasible but strongly dependent on environmental-influence quantities and setup configuration. A virtual dosimeter reflecting the prototype was created in a commercial optical modelling package. A number of virtual phantoms were developed to characterize the performance of the dosimeter under ideal conditions and with simulated disruptions in environmental-influence quantities, such as atmospheric and temperature perturbations as well as mechanical vibrations. Investigations into the error response revealed that slow drifts in atmospheric parameters and heat expansion caused the measured dose to vary between measurements, while atmospheric fluctuations and vibration contributed to system noise, significantly lowering the spatial resolution of the detector system. The impact of these effects was found to be largely mitigated with equalisation of the dosimeter's reference and object path lengths, and by miniaturising the detector. Equalising path lengths resulted in a reduction of 97.5% and 96.9% in dosimetric error introduced by heat expansion and atmospheric drift, respectively, while miniaturisation of the dosimeter was found to reduce its sensitivity to vibrations and atmospheric turbulence by up to 41.7% and 54.5%, respectively. This work represents a novel approach to optical-detector refinement in which metrics from medical imaging were adapted into software and applied to a a virtual-detector system. This methodology was found to be well-suited for the optimization of a digital holographic interferometer.

Characterization of a Bayesian network-based radiotherapy plan verification model.

PURPOSE: The current process for radiotherapy treatment plan quality assurance relies on human inspection of treatment plans, which is time-consuming, error prone and oft reliant on inconsistently applied professional judgments. A previous proof-of-principle paper describes the use of a Bayesian network (BN) to aid in this process. This work studied how such a BN could be expanded and trained to better represent clinical practice. METHODS: We obtained 51 540 unique radiotherapy cases including diagnostic, prescription, plan/beam, and therapy setup factors from a de-identified Elekta oncology information system from the years 2010-2017 from a single institution. Using a knowledge base derived from clinical experience, factors were coordinated into a 29-node, 40-edge BN representing dependencies among the variables. Conditional probabilities were machine learned using expectation maximization module using all data except a subset of 500 patient cases withheld for testing. Different classes of errors that were obtained from incident learning systems were introduced to the testing set of cases which were withheld from the dataset used for building the BN. Different sizes of datasets were used to train the network. In addition, the BN was trained using data from different length epochs as well as different eras. Its performance under these different conditions was evaluated by means of Areas Under the receiver operating characteristic Curve (AUC). RESULTS: Our performance analysis found AUCs of 0.82, 0.85, 0.89, and 0.88 in networks trained with 2-yr, 3-yr 4-yr and 5-yr windows. With a 4-yr sliding window, we found AUC reduction of 3% per year when moving the window back in time in 1-yr steps. Compared to the 4-yr window moved back by 4 yrs (2010-2013 vs 2014-2017), the largest component of overall reduction in AUC over time was from the loss of detection performance in plan/beam error types. CONCLUSIONS: The expanded BN method demonstrates the ability to detect classes of errors commonly encountered in radiotherapy planning. The results suggest that a 4-yr training dataset optimizes the performance of the network in this institutional dataset, and that yearly updates are sufficient to capture the evolution of clinical practice and maintain fidelity.

Spatially fractionated proton minibeams.

Extraordinary normal tissue response to highly spatially fractionated X-ray beams has been explored for over 25 years. More recently, alternative radiation sources have been developed and utilized with the aim to evoke comparable effects. These include protons, which lend themselves well for this endeavour due to their physical depth dose characteristics as well as corresponding variable biological effectiveness. This paper addresses the motivation for using protons to generate spatially fractionated beams and reviews the technological implementations and experimental results to date. This includes simulation and feasibility studies, collimation and beam characteristics, dosimetry and biological considerations as well as the results of in vivo and in vitro studies. Experimental results are emerging indicating an extraordinary normal tissue sparing effect analogous to what has been observed for synchrotron generated X-ray microbeams. The potential for translational research and feasibility of spatially modulated proton beams in clinical settings is discussed.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Dosimetric comparison of single-beam multi-arc and 2-beam multi-arc VMAT optimization in the Monaco treatment planning system.

The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system "max arcs-per-beam" optimization parameter in pelvic radiotherapy treatments. We selected for this study a total of 17 previously treated patients with a range of pelvic disease sites including prostate (9), bladder (1), uterus (3), rectum (3), and cervix (1). For each patient, 2 plans were generated, one using an arc-per-beam setting of "1" and another with an arc-per-beam setting of "2" using the volumes and constraints established from the initial clinical treatments. All constraints and dose coverage objects were kept the same between plans, and all plans were normalized to 99.7% to ensure 100% of the planning target volume (PTV) received 95% of the prescription dose. Plans were evaluated for PTV conformity, homogeneity, number of monitor units, number of control points, and overall plan acceptability. Treatment delivery time, patient-specific quality assurance procedures, and the impact on clinical workflow were also assessed. We found that for complex-shaped target volumes (small central volumes with extending arms to cover nodal regions), the use of 2 arc-per-beam (2APB) parameter setting achieved significantly lower average dose-volume histogram values for the rectum V20 (p = 0.0012) and bladder V30 (p = 0.0036) while meeting the high dose target constraints. For simple PTV shapes, we found reduced monitor units (13.47%, p = 0.0009) and control points (8.77%, p = 0.0004) using 2APB planning. In addition, we found a beam delivery time reduction of approximately 25%. In summary, the dosimetric benefit, although moderate, was improved over a 1APB setting for complex PTV, and equivalent in other cases. The overall reduced delivery time suggests that the use of mulitple arcs per beam could lead to reduced patient-on-table time, increased clinical throughput, and reduced medical physics quality assurance effort.