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We present the commissioning and quality assurance of our clinical protocol for respiratory gating in pencil beam scanning proton therapy for cancer patients with moving targets. In a novel approach, optical tracking has been integrated in the therapy workflow and used to monitor respiratory motion from multiple surrogates, applied on the patients' chest. The gating system was tested under a variety of experimental conditions, specific to proton therapy, to evaluate reaction time and reproducibility of dose delivery control. The system proved to be precise in the application of beam gating and allowed the mitigation of dose distortions even for large (1.4cm) motion amplitudes, provided that adequate treatment windows were selected. The total delivered dose was not affected by the use of gating, with measured integral error within 0.15cGy. Analysing high-resolution images of proton transmission, we observed negligible discrepancies in the geometric location of the dose as a function of the treatment window, with gamma pass rate greater than 95% (2%/2mm) compared to stationary conditions. Similarly, pass rate for the latter metric at the 3%/3mm level was observed above 97% for clinical treatment fields, limiting residual movement to 3mm at end-exhale. These results were confirmed in realistic clinical conditions using an anthropomorphic breathing phantom, reporting a similarly high 3%/3mm pass rate, above 98% and 94%, for regular and irregular breathing, respectively. Finally, early results from periodic QA tests of the optical tracker have shown a reliable system, with small variance observed in static and dynamic measurements., (Copyright © 2020. Published by Elsevier GmbH.)

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 (RMS Error ). For simulated field size errors, the RMS Error was 0.47 cm 2 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 cm 2 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., (© 2020 American Association of Physicists in Medicine.)

In this study, a functioning and ventilated anthropomorphic phantom was further enhanced for the purpose of CT and MR imaging of the lung and liver. A deformable lung, including respiratory tract was 3D printed. Within the lung's inner structures is a solid region shaped from a patient's lung tumour and six nitro-glycerine capsules as reference landmarks. The full internal mesh was coated, and the tumour filled, with polyorganosiloxane based gel. A moulded liver was created with an external casing of silicon filled with polyorganosiloxane gel and flexible plastic internal structures. The liver, fitted to the inferior portion of the right lung, moves along with the lung's ventilation. In the contralateral side, a cavity is designed to host a dosimeter, whose motion is correlated to the lung pressure. A 4DCT of the phantom was performed along with static and 4D T1 weighted MR images. The CT Hounsfield units (HU) for the flexible 3D printed material were -600-100 HU (lung and liver structures), for the polyorganosiloxane gel 30-120 HU (lung coating and liver filling) and for the silicon 650-800 HU (liver casing). The MR image intensity units were 0-40, 210-280 and 80-130, respectively. The maximum range of motion in the 4D imaging for the superior lung was 1-3.5 mm and 3.5-8 mm in the inferior portion. The liver motion was 5.5-8.0 mm at the tip and 5.7-10.0 mm at the dome. No measurable drift in motion was observed over a 2 h session and motion was reproducible over three different sessions for sin 2 (t), sin 4 (t) and a patient-like breathing curve with the interquartile range of amplitudes for all breathing cycles within 0.5 mm. The addition of features within the lung and of a deformable liver will allow the phantom to be used for imaging studies such as validation of 4DMRI and pseudo CT methods.

Background and Purpose: Motion management in the treatment of lung cancer is necessary to assure highest quality of the delivered radiation therapy. In this study, the breath-hold technique is experimentally investigated for pencil beam scanned (PBS) proton therapy, with respect to the dosimetric effect of residual breath-hold motion., Material and Methods: Three-dimensional (3D)-printed tumours extracted from CT scans of three patients were inserted into a dynamic anthropomorphic breathing phantom. The target was set up to move with the individual patient's tumour motion during breath-hold as previously assessed on fluoroscopy. Target dose was measured with radio-chromic film, and both single field uniform dose (SFUD) and intensity-modulated proton therapy (IMPT) plans were delivered. Experiments were repeated for each patient without any motion, to compute the relative dose deviation between static and breath-hold cases., Results: SFUD plans showed small dose deviations between static and breath-hold cases, as evidenced by the gamma pass rate (3%, 3 mm) of 85% or higher. Dose deviation was more evident for IMPT plans, with gamma pass rate reduced to 50-70%., Conclusions: The breath-hold technique is robust to residual intra-breath-hold motion for SFUD treatment plans, based on our experimental study. IMPT was less robust with larger detected dose deviations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Multileaf collimator (MLC) tracking is being clinically pioneered to continuously compensate for thoracic and pelvic motion during radiotherapy. The purpose of this work was to characterize the performance of two MLC leaf-fitting algorithms, direct optimization and piecewise optimization, for real-time motion compensation with different plan complexity and tumor trajectories., Methods: To test the algorithms, both in silico and phantom experiments were performed. The phantom experiments were performed on a Trilogy Varian linac and a HexaMotion programmable motion platform. High and low modulation VMAT plans for lung and prostate cancer cases were used along with eight patient-measured organ-specific trajectories. For both MLC leaf-fitting algorithms, the plans were run with their corresponding patient trajectories. To compare algorithms, the average exposure errors, i.e., the difference in shape between ideal and fitted MLC leaves by the algorithm, plan complexity and system latency of each experiment were calculated., Results: Comparison of exposure errors for the in silico and phantom experiments showed minor differences between the two algorithms. The average exposure errors for in silico experiments with low/high plan complexity were 0.66/0.88 cm 2 for direct optimization and 0.66/0.88 cm 2 for piecewise optimization, respectively. The average exposure errors for the phantom experiments with low/high plan complexity were 0.73/1.02 cm 2 for direct and 0.73/1.02 cm 2 for piecewise optimization, respectively. The measured latency for the direct optimization was 226 ± 10 ms and for the piecewise algorithm was 228 ± 10 ms. In silico and phantom exposure errors quantified for each treatment plan demonstrated that the exposure errors from the high plan complexity (0.96 cm 2 mean, 2.88 cm 2 95% percentile) were all significantly different from the low plan complexity (0.70 cm 2 mean, 2.18 cm 2 95% percentile) (P < 0.001, two-tailed, Mann-Whitney statistical test)., Conclusions: The comparison between the two leaf-fitting algorithms demonstrated no significant differences in exposure errors, neither in silico nor with phantom experiments. This study revealed that plan complexity impacts the overall exposure errors significantly more than the difference between the algorithms., (© 2019 American Association of Physicists in Medicine.)

This study validates a method of fast motion-including dose reconstruction for proton pencil beam scanning in the liver. The method utilizes a commercial treatment planning system (TPS) and calculates the delivered dose for any translational 3D target motion. Data from ten liver patients previously treated with photon radiotherapy with intrafraction tumour motion monitoring were used. The dose reconstruction method utilises an in-house developed program to incorporate beam's-eye-view tumour motion by shifting each spot in the opposite direction of the tumour and in-depth motion as beam energy changes for each spot. The doses are then calculated on a single CT phase in the TPS. Two aspects of the dose reconstruction were assessed: (1) The accuracy of reconstruction, by comparing dose reconstructions created using 4DCT motion with ground truth doses obtained by calculating phase specific doses in all 4DCT phases and summing up these partial doses. (2) The error caused by assuming 4DCT motion, by comparing reconstructions with 4DCT motion and actual tumour motion. The CTV homogeneity index (HI) and the root-mean-square (rms) dose error for all dose points receiving  >70%, >80% and  >90% of the prescribed dose were calculated. The dose reconstruction resulted in mean (range) absolute CTV HI errors of 1.0% (0.0-3.0)% and rms dose errors of 2.5% (1.0%-5.3%), 2.1% (0.9%-4.5%), and 1.8% (0.7%-3.7%) for  >70%, >80% and  >90% doses, respectively, when compared with the ground truth. The assumption of 4DCT motion resulted in mean (range) absolute CTV HI errors of 5.9% (0.0-15.0)% and rms dose errors of 6.3% (3.9%-12.6%), 5.9% (3.4%-12.5%), and 5.4% (2.6%-12.1%) for  >70%, >80% and  >90% doses, respectively. The investigated method allows tumour dose reconstruction with the actual tumour motion and results in significantly smaller dose errors than those caused by assuming that motion at treatment is identical to the 4DCT motion.

Purpose: To report on the primary and secondary outcomes of a prospective clinical trial of electromagnetic-guided multileaf collimator (MLC) tracking radiation therapy for prostate cancer., Methods and Materials: Twenty-eight men with prostate cancer were treated with electromagnetic-guided MLC tracking with volumetric modulated arc therapy. A total of 858 fractions were delivered, with the dose per fraction ranging from 2 to 13.75 Gy. The primary outcome was feasibility, with success determined if >95% of fractions were successfully delivered. The secondary outcomes were (1) the improvement in beam-target geometric alignment, (2) the improvement in dosimetric coverage of the prostate and avoidance of critical structures, and (3) no acute grade ≥3 genitourinary or gastrointestinal toxicity., Results: All 858 planned fractions were successfully delivered with MLC tracking, demonstrating the primary outcome of feasibility (P < .001). MLC tracking improved the beam-target geometric alignment from 1.4 to 0.90 mm (root-mean-square error). MLC tracking improved the dosimetric coverage of the prostate and reduced the daily variation in dose to critical structures. No acute grade ≥3 genitourinary or gastrointestinal toxicity was observed., Conclusions: Electromagnetic-guided MLC tracking radiation therapy for prostate cancer is feasible. The patients received improved geometric targeting and delivered dose distributions that were closer to those planned than they would have received without electromagnetic-guided MLC tracking. No significant acute toxicity was observed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inter-fraction and intra-fraction motion management methods are increasingly applied clinically and require the development of advanced motion platforms to facilitate testing and quality assurance program development. The aim of this study was to assess the performance of a 5 degrees-of-freedom (DoF) programmable motion platform HexaMotion (ScandiDos, Uppsala, Sweden) towards clinically observed tumor motion range, velocity, acceleration and the accuracy requirements of SABR prescribed in AAPM Task Group 142. Performance specifications for the motion platform were derived from literature regarding the motion characteristics of prostate and lung tumor targets required for real time motion management. The performance of the programmable motion platform was evaluated against (1) maximum range, velocity and acceleration (5 DoF), (2) static position accuracy (5 DoF) and (3) dynamic position accuracy using patient-derived prostate and lung tumor motion traces (3 DoF). Translational motion accuracy was compared against electromagnetic transponder measurements. Rotation was benchmarked with a digital inclinometer. The static accuracy and reproducibility for translation and rotation was <0.1 mm or <0.1°, respectively. The accuracy of reproducing dynamic patient motion was <0.3 mm. The motion platform's range met the need to reproduce clinically relevant translation and rotation ranges and its accuracy met the TG 142 requirements for SABR. The range, velocity and acceleration of the motion platform are sufficient to reproduce lung and prostate tumor motion for motion management. Programmable motion platforms are valuable tools in the investigation, quality assurance and commissioning of motion management systems in radiation oncology.

Purpose: Assess the dosimetric impact of multi-leaf collimator (MLC) tracking and mid-ventilation (midV) planning compared with the internal target volume (ITV)-based planning approach for lung Stereotactic Ablative Body Radiotherapy (SABR)., Method: Ten lung SABR patients originally treated with an ITV-based plan were re-planned according to MLC tracking and midV planning schemes. All plans were delivered on a linac to a motion phantom in a simulated treatment with real lung motions. Delivered dose was reconstructed in patient planning scans. ITV-based, tracking and midV regimes were compared at the planning and delivered stages based on PTV volume and dose metrics for the GTV and OAR., Results: MLC tracking and midV schemes yielded favourable outcomes compared with ITV-based plans. Average reduction in PTV volume was (MLC tracking/MidV) 33.9%/22%. GTV dose coverage performed better with MLC tracking than the other regimes. Reduction in dose to OAR were for the lung (mean lung dose, 0.8Gy/0.2Gy), oesophagus (D3cc, 1.9Gy/1.4Gy), great vessels (D10cc, 3.2Gy/1.3Gy), trachea (D4cc, 1.1Gy/0.9Gy), heart (D1cc, 2.0Gy/0.5Gy) and spinal cord (D0.03cc, 0.5Gy/-0.1Gy)., Conclusion: MLC tracking showed reduction in PTV volume, superior GTV dose coverage and organ dose sparing than MidV and ITV-based strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Intrafraction prostate motion degrades the accuracy of radiation therapy (RT) delivery. Whilst a number of metrics in the literature have been used to quantify intrafraction prostate motion, it has not been established whether these metrics reflect the effect of motion on the RT dose delivered to the patients. In this study, prostate motion during volumetric modulated arc therapy (VMAT) treatment of 18 patients and a total of 294 fractions was quantified through novel metrics as well as those available in the literature. The impact of the motion on VMAT dosimetry was evaluated using these metrics and dose reconstructions based on a previously validated and published method. The dosimetric impact of the motion on planning target volume (PTV) and clinical target volume (CTV) coverage and organs at risk (OARs) was correlated with the motion metrics, using the coefficient of determination (R 2 ), to evaluate their utility. Action level threshold for the prostate motion metric that best described the dosimetric impact on the PTV D95% was investigated through iterative regression analysis. The average (range) of the mean motion for the patient cohort was 1.5 mm (0.3-9.9 mm). A number of motion metrics were found to be strongly correlated with PTV D95%, the range of R 2 was 0.43-0.81. For all the motion measures, correlations with CTV D99% (range of R 2 was 0.12-0.62), rectum V65% (range of R 2 was 0.33-0.58) and bladder V65% (range of R 2 was 0.51-0.69) were not as strong as for PTV D95%. The mean of the highest 50% of motion metric was one of the best indicator of dosimetric impact on PTV D95%. Action level threshold value for this metric was found to be 3.0 mm. For an individual fraction, when the metric value was greater than 3.0 mm then the PTV D95% was reduced on average by 6.2%. This study demonstrated that several motion metrics are well correlated with the dosimetric impact (PTV D95%) of individual fraction prostate motion on VMAT delivery and could be used for treatment course adaptation.

Purpose: Kilovoltage intrafraction monitoring (KIM) is a new real-time 3-dimensional image guidance method. Unlike previous real-time image guidance methods, KIM uses a standard linear accelerator without any additional equipment needed. The first prospective clinical trial of KIM is underway for prostate cancer radiation therapy. In this paper we report on the measured motion accuracy and precision using real-time KIM-guided gating., Methods and Materials: Imaging and motion information from the first 200 fractions from 6 patient prostate cancer radiation therapy volumetric modulated arc therapy treatments were analyzed. A 3-mm/5-second action threshold was used to trigger a gating event where the beam is paused and the couch position adjusted to realign the prostate to the treatment isocenter. To quantify the in vivo accuracy and precision, KIM was compared with simultaneously acquired kV/MV triangulation for 187 fractions., Results: KIM was successfully used in 197 of 200 fractions. Gating events occurred in 29 fractions (14.5%). In these 29 fractions, the percentage of beam-on time, the prostate displacement was >3 mm from the isocenter position, reduced from 73% without KIM to 24% with KIM-guided gating. Displacements >5 mm were reduced from 16% without KIM to 0% with KIM. The KIM accuracy was measured at <0.3 mm in all 3 dimensions. The KIM precision was <0.6 mm in all 3 dimensions., Conclusions: Clinical implementation of real-time KIM image guidance combined with gating for prostate cancer eliminates large prostate displacements during treatment delivery. Both in vivo KIM accuracy and precision are well below 1 mm., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion., Methods and Materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded., Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate., Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: The use of a tissue expander (hydrogel) for sparing of the rectum from increased irradiation during prostate radiotherapy is becoming popular. The goal of this study is to investigate the effect of a tissue expander (hydrogel) on the intrafraction prostate motion during radiotherapy., Methods and Material: Real time prostate motion was analysed for 26 patients and 742 fractions; 12 patients with and 14 patients without hydrogel (SpaceOAR™). The intra-fraction motion was quantified and compared between the two groups., Results: The average (±standard deviation) of the mean motion during the treatment for patients with and without hydrogel was 1.5 (±0.8 mm) and 1.1 (±0.9 mm) respectively (p < 0.05). The average time of motion >3 mm for patients with and without hydrogel was 7.7 % (±1.1 %) and 4.5 % (±0.9 %) respectively (p > 0.05). The hydrogel age, fraction number and treatment time were found to have no effect (R (2)  < 0.05) on the prostate motion., Conclusions: Differences in intrafraction motion in patients with hydrogel and without hydrogel were within measurement uncertainty (<1 mm). This result confirms that the addition of a spacer does not negate the need for intrafraction motion management if clinically indicated.

Purpose: To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a prostate cancer volumetric modulated arc therapy trial., Methods and Materials: Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose that would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test., Results: Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D99% -0.8% ± 1.1% versus -2.1% ± 2.7%; CTV D99% -0.6% ± 0.8% versus -0.6% ± 1.1%; rectum V65% 1.6% ± 7.9% versus -1.2% ± 18%; and bladder V65% 0.5% ± 4.4% versus -0.0% ± 9.2% (P<.001 for all dose-volume results)., Conclusion: This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre., Methods: An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used., Results: The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion., Conclusions: The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.