The dosimetric error due to uncorrected tumor rotation during real-time adaptive prostate stereotactic body radiation therapy.

BACKGROUND: During prostate stereotactic body radiation therapy (SBRT), prostate tumor translational motion may deteriorate the planned dose distribution. Most of the major advances in motion management to date have focused on correcting this one aspect of the tumor motion, translation. However, large prostate rotation up to 30° has been measured. As the technological innovation evolves toward delivering increasingly precise radiotherapy, it is important to quantify the clinical benefit of translational and rotational motion correction over translational motion correction alone. PURPOSE: The purpose of this work was to quantify the dosimetric impact of intrafractional dynamic rotation of the prostate measured with a six degrees-of-freedom tumor motion monitoring technology. METHODS: The delivered dose was reconstructed including (a) translational and rotational motion and (b) only translational motion of the tumor for 32 prostate cancer patients recruited on a 5-fraction prostate SBRT clinical trial. Patients on the trial received 7.25 Gy in a treatment fraction. A 5 mm clinical target volume (CTV) to planning target volume (PTV) margin was applied in all directions except the posterior direction where a 3 mm expansion was used. Prostate intrafractional translational motion was managed using a gating strategy, and any translation above the gating threshold was corrected by applying an equivalent couch shift. The residual translational motion is denoted as T r e s $T_{res}$ . Prostate intrafractional rotational motion R u n c o r r $R_{uncorr}$ was recorded but not corrected. The dose differences from the planned dose due to T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ , ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and due to T r e s $T_{res}$ alone, ΔD( T r e s $T_{res}$ ), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, R u n c o r r $R_{uncorr}$ was then quantified: Δ D R e s i d u a l $\Delta D_{Residual}$ = ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) - ΔD( T res ${T}_{\textit{res}}$ ). RESULTS: Fractional data analysis shows that the dose differences from the plan (both ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ΔD( T r e s $T_{res}$ )) for CTV D98 was less than 5% in all treatment fractions. ΔD( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) was larger than 5% in one fraction for PTV D95, in one fraction for bladder V6Gy, and in five fractions for rectum V6Gy. Uncorrected rotation, R u n c o r r $R_{uncorr}$ induced residual dose error, Δ D R e s i d u a l $\Delta D_{Residual}$ , resulted in less dose to CTV and PTV in 43% and 59% treatment fractions, respectively, and more dose to bladder and rectum in 51% and 53% treatment fractions, respectively. The cumulative dose over five fractions, ∑D( T r e s $T_{res}$ + R u n c o r r $R_{uncorr}$ ) and ∑D( T r e s $T_{res}$ ), was always within 5% of the planned dose for all four structures for every patient. CONCLUSIONS: The dosimetric impact of tumor rotation on a large prostate cancer patient cohort was quantified in this study. These results suggest that the standard 3-5 mm CTV-PTV margin was sufficient to account for the intrafraction prostate rotation observed for this cohort of patients, provided an appropriate gating threshold was applied to correct for translational motion. Residual dose errors due to uncorrected prostate rotation were small in magnitude, which may be corrected using different treatment adaptation strategies to further improve the dosimetric accuracy.

Optimising multi-target multileaf collimator tracking using real-time dose for locally advanced prostate cancer patients.

Objective. The accuracy of radiotherapy for patients with locally advanced cancer is compromised by independent motion of multiple targets. To date, MLC tracking approaches have used 2D geometric optimisation where the MLC aperture shape is simply translated to correspond to the target's motion, which results in sub-optimal delivered dose. To address this limitation, a dose-optimised multi-target MLC tracking method was developed and evaluated through simulated locally advanced prostate cancer treatments.Approach. A dose-optimised multi-target tracking algorithm that adapts the MLC aperture to minimise 3D dosimetric error was developed for moving prostate and static lymph node targets. A fast dose calculation algorithm accumulated the planned dose to the prostate and lymph node volumes during treatment in real time, and the MLC apertures were recalculated to minimise the difference between the delivered and planned dose with the included motion. Dose-optimised tracking was evaluated by simulating five locally advanced prostate plans and three prostate motion traces with a relative interfraction displacement. The same simulations were performed using geometric-optimised tracking and no tracking. The dose-optimised, geometric-optimised, and no tracking results were compared with the planned doses using a 2%/2 mmγcriterion.Main results. The mean dosimetric error was lowest for dose-optimised MLC tracking, withγ-failure rates of 12% ± 8.5% for the prostate and 2.2% ± 3.2% for the nodes. Theγ-failure rates for geometric-optimised MLC tracking were 23% ± 12% for the prostate and 3.6% ± 2.5% for the nodes. When no tracking was used, theγ-failure rates were 37% ± 28% for the prostate and 24% ± 3.2% for the nodes.Significance. This study developed a dose-optimised multi-target MLC tracking method that minimises the difference between the planned and delivered doses in the presence of intrafraction motion. When applied to locally advanced prostate cancer, dose-optimised tracking showed smaller errors than geometric-optimised tracking and no tracking for both the prostate and nodes.

Comprehensive nodal breast VMAT: solving the low-dose wash dilemma using an iterative knowledge-based radiotherapy planning solution.

INTRODUCTION: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash. METHODS: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. RESULTS: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. CONCLUSIONS: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk.

First experimental evaluation of multi-target multileaf collimator tracking during volumetric modulated arc therapy for locally advanced prostate cancer.

PURPOSE: Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. METHODS: Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. RESULTS: The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. CONCLUSION: This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking.

Radiotherapy dose calculations in high-Z materials: comprehensive comparison between experiment, Monte Carlo, and conventional planning algorithms.

Purpose. To compare the accuracies of the AAA and AcurosXB dose calculation algorithms and to predict the change in the down-stream and lateral dose deposition of high energy photons in the presence of material with densities higher that commonly found in the body.Method. Metal rods of titanium (d = 4.5 g cm-3), stainless steel (d = 8 g cm-3) and tungsten (d = 19.25 g cm-3) were positioned in a phantom. Film was position behind and laterally to the rods to measure the dose distribution for a 6 MV, 18 MV and 10 FFF photon beams. A DOSXYZnrc Monte Carlo simulation of the experimental setup was performed. The AAA and AcurosXB dose calculation algorithms were used to predict the dose distributions. The dose from film and DOSXYZnrc were compared with the dose predicted by AAA and AcurosXB.Results. AAA overestimated the dose behind the rods by 15%-25% and underestimated the dose laterally to the rods by 5%-15% depending on the range of materials and energies investigated. AcurosXB overestimated the dose behind the rods by 1%-18% and underestimated the dose laterally to the rods by up to 5% depending on the range of material and energies investigated.Conclusion. AAA cannot deliver clinically acceptable dose calculation results at a distance less than 10 mm from metals, for a single field treatment. Acuros XB is able to handle metals of low atomic numbers (Z ≤ 26), but not tungsten (Z = 74). This can be due to the restriction of the CT-density table in EclipseTMTPS, which has an upper HU limit of 10501.

Adapting to the motion of multiple independent targets using multileaf collimator tracking for locally advanced prostate cancer: Proof of principle simulation study.

PURPOSE: For patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer. METHODS: A multi-target MLC tracking algorithm was developed that consisted of three steps: (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods: single-target tracking and no tracking. Treatment simulations of six locally advanced prostate cancer patients with three prostate motion traces were performed for all three motion adaptation methods. The geometric error for each motion adaptation method was calculated using the area of overexposure and underexposure of each field. The dosimetric error was estimated by calculating the dose delivered to the prostate, lymph nodes, bladder, rectum, and small bowel using a motion-encoded dose reconstruction method. RESULTS: Multi-target MLC tracking showed an average improvement in geometric error of 84% compared to single-target tracking, and 83% compared to no tracking. Multi-target tracking maintained dose coverage to the prostate clinical target volume (CTV) D98% and planning target volume (PTV) D95% to within 4.8% and 3.9% of the planned values, compared to 1.4% and 0.7% with single-target tracking, and 20.4% and 31.8% with no tracking. With multi-target tracking, the node CTV D95%, PTV D90%, and gross tumor volume (GTV) D95% were within 0.3%, 0.6%, and 0.3% of the planned values, compared to 9.1%, 11.2%, and 21.1% for single-target tracking, and 0.8%, 2.0%, and 3.2% with no tracking. The small bowel V57% was maintained within 0.2% to the plan using multi-target tracking, compared to 8% and 3.5% for single-target tracking and no tracking, respectively. Meanwhile, the bladder and rectum V50% increased by up to 13.6% and 5.2%, respectively, using multi-target tracking, compared to 2.7% and 1.9% for single-target tracking, and 11.2% and 11.5% for no tracking. CONCLUSIONS: A multi-target tracking algorithm was developed and tracked the prostate and lymph nodes independently during simulated treatments. As the algorithm optimizes for target coverage, tracking both targets simultaneously may increase the dose delivered to the organs at risk.

Toward real-time verification for MLC tracking treatments using time-resolved EPID imaging.

PURPOSE: In multileaf collimator (MLC) tracking, the MLC positions from the original treatment plan are continuously modified to account for intrafraction tumor motion. As the treatment is adapted in real time, there is additional risk of delivery errors which cannot be detected using traditional pretreatment dose verification. The purpose of this work is to develop a system for real-time geometric verification of MLC tracking treatments using an electronic portal imaging device (EPID). METHODS: MLC tracking was utilized during volumetric modulated arc therapy (VMAT). During these deliveries, treatment beam images were taken at 9.57 frames per second using an EPID and frame grabber computer. MLC positions were extracted from each image frame and used to assess delivery accuracy using three geometric measures: the location, size, and shape of the radiation field. The EPID-measured field location was compared to the tumor motion measured by implanted electromagnetic markers. The size and shape of the beam were compared to the size and shape from the original treatment plan, respectively. This technique was validated by simulating errors in phantom test deliveries and by comparison between EPID measurements and treatment log files. The method was applied offline to images acquired during the LIGHT Stereotactic Ablative Body Radiotherapy (SABR) clinical trial, where MLC tracking was performed for 17 lung cancer patients. The EPID-based verification results were subsequently compared to post-treatment dose reconstruction. RESULTS: Simulated field location errors were detected during phantom validation tests with an uncertainty of 0.28 mm (parallel to MLC motion) and 0.38 mm (perpendicular), expressed as a root-mean-square error (RMSError ). For simulated field size errors, the RMSError was 0.47 cm2 and field shape changes were detected for random errors with standard deviation ≥ 2.5 mm. For clinical lung SABR deliveries, field location errors of 1.6 mm (parallel MLC motion) and 4.9 mm (perpendicular) were measured (expressed as a full-width-half-maximum). The mean and standard deviation of the errors in field size and shape were 0.0 ± 0.3 cm2 and 0.3 ± 0.1 (expressed as a translation-invariant normalized RMS). No correlation was observed between geometric errors during each treatment fraction and dosimetric errors in the reconstructed dose to the target volume for this cohort of patients. CONCLUSION: A system for real-time delivery verification has been developed for MLC tracking using time-resolved EPID imaging. The technique has been tested offline in phantom-based deliveries and clinical patient deliveries and was used to independently verify the geometric accuracy of the MLC during MLC tracking radiotherapy.

AAPM Task Group 264: The safe clinical implementation of MLC tracking in radiotherapy.

The era of real-time radiotherapy is upon us. Robotic and gimbaled linac tracking are clinically established technologies with the clinical realization of couch tracking in development. Multileaf collimators (MLCs) are a standard equipment for most cancer radiotherapy systems, and therefore MLC tracking is a potentially widely available technology. MLC tracking has been the subject of theoretical and experimental research for decades and was first implemented for patient treatments in 2013. The AAPM Task Group 264 Safe Clinical Implementation of MLC Tracking in Radiotherapy Report was charged to proactively provide the broader radiation oncology community with (a) clinical implementation guidelines including hardware, software, and clinical indications for use, (b) commissioning and quality assurance recommendations based on early user experience, as well as guidelines on Failure Mode and Effects Analysis, and (c) a discussion of potential future developments. The deliverables from this report include: an explanation of MLC tracking and its historical development; terms and definitions relevant to MLC tracking; the clinical benefit of, clinical experience with and clinical implementation guidelines for MLC tracking; quality assurance guidelines, including example quality assurance worksheets; a clinical decision pathway, future outlook and overall recommendations.

Is multileaf collimator tracking or gating a better intrafraction motion adaptation strategy? An analysis of the TROG 15.01 stereotactic prostate ablative radiotherapy with KIM (SPARK) trial.

PURPOSE: Stereotactic Ablative Radiotherapy (SABR) has recently emerged as a favourable treatment option for prostate cancer patients. With higher doses delivered over fewer fractions, motion adaptation is a requirement for accurate delivery of SABR. This study compared the efficacy of multileaf collimator (MLC) tracking vs. gating as a real-time motion adaptation strategy for prostate SABR patients enrolled in a clinical trial. METHODS: Forty-four prostate cancer patients treated over five fractions in the TROG 15.01 SPARK trial were analysed in this study. Forty-nine fractions were treated using MLC tracking and 166 fractions were treated using beam gating and couch shifts. A time-resolved motion-encoded dose reconstruction method was used to evaluate the dose delivered using each motion adaptation strategy and compared to an estimation of what would have been delivered with no motion adaptation strategy implemented. RESULTS: MLC tracking and gating both delivered doses closer to the plan compared to when no motion adaptation strategy was used. Differences between MLC tracking and gating were small with differences in the mean discrepancy from the plan of -0.3% (CTV D98%), 1.4% (CTV D2%), 0.4% (PTV D95%), 0.2% (rectum V30Gy) and 0.0% (bladder V30Gy). On average, 0.5 couch shifts were required per gated fractions with a mean interruption duration of 1.8 ± 2.6 min per fraction treated using gating. CONCLUSION: Both MLC tracking and gating were effective strategies at improving the accuracy of the dose delivered to the target and organs at risk. While dosimetric performance was comparable, gating resulted in interruptions to treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT02397317.

Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part I: Intra-fraction breathing motion management.

PURPOSE: The POP-ART RT study aims to determine to what extent and how intra-fractional real-time respiratory motion management (RRMM) and plan adaptation for inter-fractional anatomical changes (ART), are used in clinical practice and to understand barriers to implementation. Here we report on part I: RRMM. MATERIAL AND METHODS: A questionnaire was distributed worldwide to assess current clinical practice, wishes for expansion or new implementation and barriers to implementation. RRMM was defined as inspiration/expiration gating in free-breathing or breath-hold, or tracking where the target and the beam are continuously realigned. RESULTS: The questionnaire was completed by 200 centres from 41 countries. RRMM was used by 68% of respondents ('users') for a median (range) of 2 (1-6) tumour sites. Eighty-one percent of users applied inspiration breath-hold in at least one tumour site (breast: 96%). External marker was used to guide RRMM by 61% of users. KV/MV imaging was frequently used for liver and pancreas (with fiducials) and for lung (with or without fiducials). Tracking was mainly performed on robotic linacs with hybrid internal-external monitoring. For breast and lung, approximately 75% of respondents used or wished to implement RRMM, which was lower for liver (44%) and pancreas (27%). Seventy-one percent of respondents wished to implement RRMM for a new tumour site. Main barriers were human/financial resources and capacity on the machine. CONCLUSION: Sixty-eight percent of respondents used RRMM and 71% wished to implement RRMM for a new tumour site. The main barriers to implementation were human/financial resources and capacity on treatment machines.

Water equivalence of a solid phantom material for radiation dosimetry applications.

Radiological water equivalence of solid phantoms used for radiotherapy is often desired, but is non-trivial to achieve across the range of therapeutic energies. This study evaluated the water equivalence of a new solid phantom material in beam qualities relevant to radiotherapy applications. In-phantom measured depth distributions were compared to that in water to assess the relative attenuation and scatter characteristics of the material. The phantom material was found to be dosimetrically equivalent to water within (1.0 ± 1.0)% for megavoltage photon beam qualities, (1.5 ± 1.3)% for megavoltage electron beam qualities, (1.5 ± 1.5)% for medium-energy kilovoltage X-rays and (3.0 ± 1.5)% for low-energy kilovoltage X-rays.

The accuracy and precision of the KIM motion monitoring system used in the multi-institutional TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with KIM (SPARK) trial.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) allows for real-time image guidance for tracking tumor motion in six-degrees-of-freedom (6DoF) on a standard linear accelerator. This study assessed the geometric accuracy and precision of KIM used to guide patient treatments in the TROG 15.01 multi-institutional Stereotactic Prostate Ablative Radiotherapy with KIM trial and investigated factors affecting accuracy and precision. METHODS: Fractions from 44 patients with prostate cancer treated using KIM-guided SBRT were analyzed across four institutions, on two different linear accelerator models and two different beam models (6 MV and 10 MV FFF). The geometric accuracy and precision of KIM was assessed from over 33 000 images (translation) and over 9000 images (rotation) by comparing the real-time measured motion to retrospective kV/MV triangulation. Factors potentially affecting accuracy, including contrast-to-noise ratio (CNR) of kV images and incorrect marker segmentation, were also investigated. RESULTS: The geometric accuracy and precision did not depend on treatment institution, beam model or motion magnitude, but was correlated with gantry angle. The centroid geometric accuracy and precision of the KIM system for SABR prostate treatments was 0.0 ± 0.5, 0.0 ± 0.4 and 0.1 ± 0.3 mm for translation, and -0.1 ± 0.6°, -0.1 ± 1.4° and -0.1 ± 1.0° for rotation in the AP, LR and SI directions respectively. Centroid geometric error exceeded 2 mm for 0.05% of this dataset. No significant relationship was found between large geometric error and CNR or marker segmentation correlation. CONCLUSIONS: This study demonstrated the ability of KIM to locate the prostate with accuracy below other uncertainties in radiotherapy treatments, and the feasibility for KIM to be implemented across multiple institutions.

See, Think, and Act: Real-Time Adaptive Radiotherapy.

The world is embracing the information age, with real-time data at hand to assist with many decisions. Similarly, in cancer radiotherapy we are inexorably moving toward using information in a smarter and faster fashion, to usher in the age of real-time adaptive radiotherapy. The three critical steps of real-time adaptive radiotherapy, aligned with driverless vehicle technology are a continuous see, think, and act loop. See: use imaging systems to probe the patient anatomy or physiology as it evolves with time. Think: use current and prior information to optimize the treatment using the available adaptive degrees of freedom. Act: deliver the real-time adapted treatment. This paper expands upon these three critical steps for real-time adaptive radiotherapy, provides a historical context, reviews the clinical rationale, and gives a future outlook for real-time adaptive radiotherapy.

A deep learning framework for automatic detection of arbitrarily shaped fiducial markers in intrafraction fluoroscopic images.

PURPOSE: Real-time image-guided adaptive radiation therapy (IGART) requires accurate marker segmentation to resolve three-dimensional (3D) motion based on two-dimensional (2D) fluoroscopic images. Most common marker segmentation methods require prior knowledge of marker properties to construct a template. If marker properties are not known, an additional learning period is required to build the template which exposes the patient to an additional imaging dose. This work investigates a deep learning-based fiducial marker classifier for use in real-time IGART that requires no prior patient-specific data or additional learning periods. The proposed tracking system uses convolutional neural network (CNN) models to segment cylindrical and arbitrarily shaped fiducial markers. METHODS: The tracking system uses a tracking window approach to perform sliding window classification of each implanted marker. Three cylindrical marker training datasets were generated from phantom kilovoltage (kV) and patient intrafraction images with increasing levels of megavoltage (MV) scatter. The cylindrical shaped marker CNNs were validated on unseen kV fluoroscopic images from 12 fractions of 10 prostate cancer patients with implanted gold fiducials. For the training and validation of the arbitrarily shaped marker CNNs, cone beam computed tomography (CBCT) projection images from ten fractions of seven lung cancer patients with implanted coiled markers were used. The arbitrarily shaped marker CNNs were trained using three patients and the other four unseen patients were used for validation. The effects of full training using a compact CNN (four layers with learnable weights) and transfer learning using a pretrained CNN (AlexNet, eight layers with learnable weights) were analyzed. Each CNN was evaluated using a Precision-Recall curve (PRC), the area under the PRC plot (AUC), and by the calculation of sensitivity and specificity. The tracking system was assessed using the validation data and the accuracy was quantified by calculating the mean error, root-mean-square error (RMSE) and the 1st and 99th percentiles of the error. RESULTS: The fully trained CNN on the dataset with moderate noise levels had a sensitivity of 99.00% and specificity of 98.92%. Transfer learning of AlexNet resulted in a sensitivity and specificity of 99.42% and 98.13%, respectively, for the same datasets. For the arbitrarily shaped marker CNNs, the sensitivity was 98.58% and specificity was 98.97% for the fully trained CNN. The transfer learning CNN had a sensitivity and specificity of 98.49% and 99.56%, respectively. The CNNs were successfully incorporated into a multiple object tracking system for both cylindrical and arbitrarily shaped markers. The cylindrical shaped marker tracking had a mean RMSE of 1.6 ± 0.2 pixels and 1.3 ± 0.4 pixels in the x- and y-directions, respectively. The arbitrarily shaped marker tracking had a mean RMSE of 3.0 ± 0.5 pixels and 2.2 ± 0.4 pixels in the x- and y-directions, respectively. CONCLUSION: With deep learning CNNs, high classification performances on unseen patient images were achieved for both cylindrical and arbitrarily shaped markers. Furthermore, the application of CNN models to intrafraction monitoring was demonstrated using a simple tracking system. The results demonstrate that CNN models can be used to track markers without prior knowledge of the marker properties or an additional learning period.

A six-degree-of-freedom robotic motion system for quality assurance of real-time image-guided radiotherapy.

In this study we develop and characterise a six degree-of-freedom (6 DoF) robotic motion system for quality assurance of real-time image-guided radiotherapy techniques. The system consists of a commercially available robotic arm, an acrylic phantom with embedded Calypso markers, a custom base plate to mount the robot to the treatment couch, and control software implementing the appropriate sequence of transformations to reproduce measured tumour motion traces. The robotic motion system was evaluated in terms of the set-up and motion trace repeatability, static localization accuracy and dynamic localization accuracy. Four prostate, two liver and three lung motion traces, representing a range of tumor motion trajectories recorded in real patient treatments, were executed using the robotic motion system and compared with motion measurements from the clinical Calypso motion tracking system. System set-up and motion trace repeatability was better than 0.5 deg and 0.3 mm for rotation and translation, respectively. The static localization accuracy of the robotic motion system in the LR, SI and AP directions was 0.09 mm, 0.08 mm and 0.02 mm for translations, respectively, and 0.2°, 0.06° and 0.06° for rotations, respectively. The dynamic localization accuracy of the robotic motion system was <0.2 mm and <0.6° for translations and rotations, respectively. Thus, we have demonstrated the ability to accurately mimic rigid-body tumor motion using a robotically controlled phantom to provide precise geometric QA for advanced radiotherapy delivery approaches.

The VAMPIRE challenge: A multi-institutional validation study of CT ventilation imaging.

PURPOSE: CT ventilation imaging (CTVI) is being used to achieve functional avoidance lung cancer radiation therapy in three clinical trials (NCT02528942, NCT02308709, NCT02843568). To address the need for common CTVI validation tools, we have built the Ventilation And Medical Pulmonary Image Registration Evaluation (VAMPIRE) Dataset, and present the results of the first VAMPIRE Challenge to compare relative ventilation distributions between different CTVI algorithms and other established ventilation imaging modalities. METHODS: The VAMPIRE Dataset includes 50 pairs of 4DCT scans and corresponding clinical or experimental ventilation scans, referred to as reference ventilation images (RefVIs). The dataset includes 25 humans imaged with Galligas 4DPET/CT, 21 humans imaged with DTPA-SPECT, and 4 sheep imaged with Xenon-CT. For the VAMPIRE Challenge, 16 subjects were allocated to a training group (with RefVI provided) and 34 subjects were allocated to a validation group (with RefVI blinded). Seven research groups downloaded the Challenge dataset and uploaded CTVIs based on deformable image registration (DIR) between the 4DCT inhale/exhale phases. Participants used DIR methods broadly classified into B-splines, Free-form, Diffeomorphisms, or Biomechanical modeling, with CT ventilation metrics based on the DIR evaluation of volume change, Hounsfield Unit change, or various hybrid approaches. All CTVIs were evaluated against the corresponding RefVI using the voxel-wise Spearman coefficient rS , and Dice similarity coefficients evaluated for low function lung ( DSClow ) and high function lung ( DSChigh ). RESULTS: A total of 37 unique combinations of DIR method and CT ventilation metric were either submitted by participants directly or derived from participant-submitted DIR motion fields using the in-house software, VESPIR. The rS and DSC results reveal a high degree of inter-algorithm and intersubject variability among the validation subjects, with algorithm rankings changing by up to ten positions depending on the choice of evaluation metric. The algorithm with the highest overall cross-modality correlations used a biomechanical model-based DIR with a hybrid ventilation metric, achieving a median (range) of 0.49 (0.27-0.73) for rS , 0.52 (0.36-0.67) for DSClow , and 0.45 (0.28-0.62) for DSChigh . All other algorithms exhibited at least one negative rS value, and/or one DSC value less than 0.5. CONCLUSIONS: The VAMPIRE Challenge results demonstrate that the cross-modality correlation between CTVIs and the RefVIs varies not only with the choice of CTVI algorithm but also with the choice of RefVI modality, imaging subject, and the evaluation metric used to compare relative ventilation distributions. This variability may arise from the fact that each of the different CTVI algorithms and RefVI modalities provides a distinct physiologic measurement. Ultimately this variability, coupled with the lack of a "gold standard," highlights the ongoing importance of further validation studies before CTVI can be widely translated from academic centers to the clinic. It is hoped that the information gleaned from the VAMPIRE Challenge can help inform future validation efforts.

An augmented correlation framework for the estimation of tumour translational and rotational motion during external beam radiotherapy treatments using intermittent monoscopic x-ray imaging and an external respiratory signal.

Increasing evidence shows that intrafraction tumour motion monitoring must include both six degrees of freedom (6DoF): 3D translations and 3D rotations. Existing real-time algorithms for 6DoF target motion estimation require continuous intrafraction fluoroscopic imaging at high frequency, thereby exposing patients to additional high imaging dose. This paper presents the first method capable of 6DoF motion monitoring using intermittent 2D kV imaging and a continuous external respiratory signal. Our approach is to optimise a state-augmented linear correlation model between an external signal and internal 6DoF motion. In standard treatments, the model can be built using information obtained during pre-treatment cone beam CT (CBCT). Real-time 6DoF tumor motion can then be estimated using just the external signal. Intermittent intrafraction kV images are used to update the model parameters, accounting for changes in correlation and baseline shifts. The method was evaluated in silico using data from 6 lung SABR patients, with the internal tumour motion recorded with electromagnetic beacons and the external signal from a bellows belt. Projection images from CBCT (10 Hz) and intermittent kV images were simulated by projecting the 3D Calypso beacon positions onto an imager. IMRT and VMAT treatments were simulated with increasing imaging update intervals: 0.1 s, 1 s, 3 s, 10 s and 30 s. For all the tested clinical scenarios, translational motion estimates with our method had sub-mm accuracy (mean) and precision (standard deviation) while rotational motion estimates were accurate to <[Formula: see text] and precise to [Formula: see text]. Motion estimation errors increased as the imaging update interval increased. With the largest imaging update interval (30 s), the errors were [Formula: see text] mm, [Formula: see text] mm and [Formula: see text] mm for translation in the left-right, superior-inferior and anterior-posterior directions, respectively, and [Formula: see text], [Formula: see text] and [Formula: see text] for rotation around the aforementioned axes for both VMAT and IMRT treatments. In conclusion, we developed and evaluated a novel method for highly accurate real-time 6DoF motion monitoring on a standard linear accelerator without requiring continuous kV imaging. The proposed method achieved sub-mm and sub-degree accuracy on a lung cancer patient dataset.

Real-time high spatial resolution dose verification in stereotactic motion adaptive arc radiotherapy.

PURPOSE: Radiation treatments delivered with real-time multileaf collimator (MLC) tracking currently lack fast pretreatment or real-time quality assurance. The purpose of this study is to test a 2D silicon detector, MagicPlate-512 (MP512), in a complex clinical environment involving real-time reconfiguration of the MLC leaves during target tracking. METHODS: MP512 was placed in the center of a solid water phantom and mounted on a motion platform used to simulate three different patient motions. Electromagnetic target tracking was implemented using the Calypso system (Varian Medical Systems, Palo Alto, CA, USA) and an MLC tracking software. A two-arc VMAT plan was delivered and 2D dose distributions were reconstructed by MP512, EBT3 film, and the Eclipse treatment planning system (TPS). Dose maps were compared using gamma analysis with 2%/2 mm and 3%/3 mm acceptance criteria. Dose profiles were generated in sup-inf and lateral directions to show the agreement of MP512 to EBT3 and to highlight the efficacy of the MLC tracking system in mitigating the effect of the simulated patient motion. RESULTS: Using a 3%/3 mm acceptance criterion for 2D gamma analysis, MP512 to EBT3 film agreement was 99% and MP512 to TPS agreement was 100%. For a 2%/2 mm criterion, the agreement was 95% and 98%, respectively. Full width at half maximum and 80%/20% penumbral width of the MP512 and EBT3 dose profiles agreed within 1 mm and 0.5 mm, respectively. Patient motion increased the measured dose profile penumbral width by nearly 2 mm (with respect to the no-motion case); however, the MLC tracking strategy was able to mitigate 80% of this effect. CONCLUSIONS: MP512 is capable of high spatial resolution 2D dose reconstruction during adaptive MLC tracking, including arc deliveries. It shows potential as an effective tool for 2D small field dosimetry and pretreatment quality assurance for MLC tracking modalities. These results provide confidence that detector-based pretreatment dosimetry is clinically feasible despite fast real-time MLC reconfigurations.

The accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom prostate motion measurements during patient treatments.

BACKGROUND AND PURPOSE: To perform a quantitative analysis of the accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom (6DoF) prostate motion measurements during treatments. MATERIAL AND METHODS: Real-time 6DoF prostate motion was acquired using KIM for 14 prostate cancer patients (377 fractions). KIM outputs the 6DoF prostate motion, combining 3D translation and 3D rotational motion information relative to its planning position. The corresponding groundtruth target motion was obtained post-treatment based on kV/MV triangulation. The accuracy and precision of the 6DoF KIM motion estimates were calculated as the mean and standard deviation differences compared with the ground-truth. RESULTS: The accuracy ±â€¯precision of real-time 6DoF KIM-measured prostate motion were 0.2 ±â€¯1.3° for rotations and 0.1 ±â€¯0.5 mm for translations, respectively. The magnitude of KIM-measured motion was well-correlated with the magnitude of ground-truth motion resulting in Pearson correlation coefficients of  ≥0.88 in all DoF. CONCLUSIONS: The results demonstrate that KIM is capable of providing the real-time 6DoF prostate target motion during patient treatments with an accuracy ±â€¯precision of within 0.2 ±â€¯1.3° and 0.1 ±â€¯0.5 mm for rotation and translation, respectively. As KIM only requires a single X-ray imager, which is available on most modern cancer radiotherapy devices, there is potential for widespread adoption of this technology.

The first clinical implementation of real-time image-guided adaptive radiotherapy using a standard linear accelerator.

PURPOSE: Until now, real-time image guided adaptive radiation therapy (IGART) has been the domain of dedicated cancer radiotherapy systems. The purpose of this study was to clinically implement and investigate real-time IGART using a standard linear accelerator. MATERIALS/METHODS: We developed and implemented two real-time technologies for standard linear accelerators: (1) Kilovoltage Intrafraction Monitoring (KIM) that finds the target and (2) multileaf collimator (MLC) tracking that aligns the radiation beam to the target. Eight prostate SABR patients were treated with this real-time IGART technology. The feasibility, geometric accuracy and the dosimetric fidelity were measured. RESULTS: Thirty-nine out of forty fractions with real-time IGART were successful (95% confidence interval 87-100%). The geometric accuracy of the KIM system was -0.1 ±â€¯0.4, 0.2 ±â€¯0.2 and -0.1 ±â€¯0.6 mm in the LR, SI and AP directions, respectively. The dose reconstruction showed that real-time IGART more closely reproduced the planned dose than that without IGART. For the largest motion fraction, with real-time IGART 100% of the CTV received the prescribed dose; without real-time IGART only 95% of the CTV would have received the prescribed dose. CONCLUSION: The clinical implementation of real-time image-guided adaptive radiotherapy on a standard linear accelerator using KIM and MLC tracking is feasible. This achievement paves the way for real-time IGART to be a mainstream treatment option.