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Cone‐beam CT (CBCT) is the most commonly used onboard imaging technique for target localization in radiation therapy. Conventional 3D CBCT acquires x‐ray cone‐beam projections at multiple angles around the patient to reconstruct 3D images of the patient in the treatment room. However, despite its wide usage, 3D CBCT is limited in imaging disease sites affected by respiratory motions or other dynamic changes within the body, as it lacks time‐resolved information. To overcome this limitation, 4D‐CBCT was developed to incorporate a time dimension in the imaging to account for the patient's motion during the acquisitions. For example, respiration‐correlated 4D‐CBCT divides the breathing cycles into different phase bins and reconstructs 3D images for each phase bin, ultimately generating a complete set of 4D images. 4D‐CBCT is valuable for localizing tumors in the thoracic and abdominal regions where the localization accuracy is affected by respiratory motions. This is especially important for hypofractionated stereotactic body radiation therapy (SBRT), which delivers much higher fractional doses in fewer fractions than conventional fractionated treatments. Nonetheless, 4D‐CBCT does face certain limitations, including long scanning times, high imaging doses, and compromised image quality due to the necessity of acquiring sufficient x‐ray projections for each respiratory phase. In order to address these challenges, numerous methods have been developed to achieve fast, low‐dose, and high‐quality 4D‐CBCT. This paper aims to review the technical developments surrounding 4D‐CBCT comprehensively. It will explore conventional algorithms and recent deep learning‐based approaches, delving into their capabilities and limitations. Additionally, the paper will discuss the potential clinical applications of 4D‐CBCT and outline a future roadmap, highlighting areas for further research and development. Through this exploration, the readers will better understand 4D‐CBCT's capabilities and potential to enhance radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Data‐driven gated (DDG) PET has gained clinical acceptance and has been shown to match or outperform external‐device gated (EDG) PET. However, in most clinical applications, DDG PET is matched with helical CT acquired in free breathing (FB) at a random respiratory phase, leaving registration, and optimal attenuation correction (AC) to chance. Furthermore, DDG PET requires additional scan time to reduce image noise as it only preserves 35%–50% of the PET data at or near the end‐expiratory phase of the breathing cycle. Purpose: A new full‐counts, phase‐matched (FCPM) DDG PET/CT was developed based on a low‐dose cine CT to improve registration between DDG PET and DDG CT, to reduce image noise, and to avoid increasing acquisition times in DDG PET. Methods: A new DDG CT was developed for three respiratory phases of CT images from a low dose cine CT acquisition of 1.35 mSv for a coverage of about 15.4 cm: end‐inspiration (EI), average (AVG), and end‐expiration (EE) to match with the three corresponding phases of DDG PET data: −10% to 15%; 15% to 30%, and 80% to 90%; and 30% to 80%, respectively. The EI and EE phases of DDG CT were selected based on the physiological changes in lung density and body outlines reflected in the dynamic cine CT images. The AVG phase was derived from averaging of all phases of the cine CT images. The cine CT was acquired over the lower lungs and/or upper abdomen for correction of misregistration between PET and FB CT as well as DDG PET and FB CT. The three phases of DDG CT were used for AC of the corresponding phases of PET. After phase‐matched AC of each PET dataset, the EI and AVG PET data were registered to the EE PET data with deformable image registration. The final result was FCPM DDG PET/CT which accounts for all PET data registered at the EE phase. We applied this approach to 14 18F‐FDG lung cancer patient studies acquired at 2 min/bed position on the GE Discovery MI (25‐cm axial FOV) and evaluated its efficacy in improved quantification and noise reduction. Results: Relative to static PET/CT, the SUVmax increases for the EI, AVG, EE, and FCPM DDG PET/CT were 1.67 ± 0.40, 1.50 ± 0.28, 1.64 ± 0.36, and 1.49 ± 0.28, respectively. There were 10.8% and 9.1% average decreases in SUVmax from EI and EE to FCPM DDG PET/CT, respectively. EI, AVG, and EE DDG PET/CT all maintained increased image noise relative to static PET/CT. However, the noise levels of FCPM and static PET were statistically equivalent, suggesting the inclusion of all counts was able to decrease the image noise relative to EI and EE DDG PET/CT. Conclusions: A new FCPM DDG PET/CT has been developed to account for 100% of collected PET data in DDG PET applications. Image noise in FCPM is comparable to static PET, while small decreases in SUVmax were also observed in FCPM when compared to either EI or EE DDG PET/CT. [ABSTRACT FROM AUTHOR]

Background: Time‐resolved magnetic resonance fingerprinting (MRF), or 4D‐MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D‐MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. Purpose: To develop a technique for the reconstruction of multi‐phase parametric maps in four‐dimensional magnetic resonance fingerprinting (4D‐MRF) through the optimization of local T1 and T2 sensitivities. Methods: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter‐phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi‐phase signal evolution curves were modified by sliding window reconstruction and inter‐phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi‐parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac‐torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. Results: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight‐phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in‐vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. Conclusions: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi‐phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data. [ABSTRACT FROM AUTHOR]

Background: Volumetric reconstruction of magnetic resonance imaging (MRI) from sparse samples is desirable for 3D motion tracking and promises to improve magnetic resonance (MR)‐guided radiation treatment precision. Data‐driven sparse MRI reconstruction, however, requires large‐scale training datasets for prior learning, which is time‐consuming and challenging to acquire in clinical settings. Purpose: To investigate volumetric reconstruction of MRI from sparse samples of two orthogonal slices aided by sparse priors of two static 3D MRI through implicit neural representation (NeRP) learning, in support of 3D motion tracking during MR‐guided radiotherapy. Methods: A multi‐layer perceptron network was trained to parameterize the NeRP model of a patient‐specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first training the network to learn the NeRP of two static 3D MRI with different breathing motion states, prior information of patient breathing motion was embedded into network weights through optimization. The prior information was then augmented from two motion states to 31 motion states by querying the optimized network at interpolated and extrapolated motion state coordinates. Starting from the prior‐augmented NeRP model as an initialization point, we further trained the network to fit sparse samples of two orthogonal MRI slices and the final volumetric reconstruction was obtained by querying the trained network at 3D spatial locations. We evaluated the proposed method using 5‐min volumetric MRI time series with 340 ms temporal resolution for seven abdominal patients with hepatocellular carcinoma, acquired using golden‐angle radial MRI sequence and reconstructed through retrospective sorting. Two volumetric MRI with inhale and exhale states respectively were selected from the first 30 s of the time series for prior embedding and augmentation. The remaining 4.5‐min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to two orthogonal slices and compared model‐reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. Results: Across the seven patients evaluated, the peak signal‐to‐noise‐ratio between model‐reconstructed and ground truth MR images was 38.02 ± 2.60 dB and the structure similarity index measure was 0.98 ± 0.01. Throughout the 4.5‐min time period, gross tumor volume (GTV) motion estimated by deforming a reference state MRI to model‐reconstructed and ground truth MRI showed good consistency. The 95‐percentile Hausdorff distance between GTV contours was 2.41 ± 0.77 mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1 mm in all three orthogonal directions. Conclusion: A prior‐augmented NeRP model has been developed to reconstruct volumetric MRI from sparse samples of orthogonal cine slices. Only one exhale and one inhale 3D MRI were needed to train the model to learn prior information of patient breathing motion for sparse image reconstruction. The proposed model has the potential of supporting 3D motion tracking during MR‐guided radiotherapy for improved treatment precision and promises a major simplification of the workflow by eliminating the need for large‐scale training datasets. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of a thermo-optical surface imaging (SGRT) system combined with room-based stereoscopic X‑ray image guidance (IGRT) in a dedicated breast deep inspiration breath-hold (DIBH) irradiation workflow. In this context, benchmarking of portal imaging (EPID) and cone-beam CT (CBCT) against stereoscopic X‑rays was performed. Methods: SGRT + IGRT data of 30 left-sided DIBH breast patients (1 patient with bilateral cancer) treated in 351 fractions using thermo-optical surface imaging and X-ray IGRT were retrospectively analysed. Patients were prepositioned based on a free-breathing surface reference derived from a CT scan. Once the DIBH was reached using visual feedback, two stereoscopic X‑ray images were acquired and registered to the digitally reconstructed radiographs derived from the DIBH CT. Based on this registration, a couch correction was performed. Positioning and monitoring by surface and X-ray imaging were verified by protocol-based EPID or CBCT imaging at selected fractions and the calculation of residual geometric deviations. Results: The median X‑ray-derived couch correction vector was 4.9 (interquartile range [IQR] 3.3–7.1) mm long. Verification imaging was performed for 134 fractions (216 RT field verifications) with EPID and for 37 fractions with CBCT, respectively. The median 2D/3D deviation vector length over all verification images was 2.5 (IQR 1.6–3.9) mm/3.4 (IQR 2.2–4.8) mm for EPID/CBCT, both being well within the planning target volume (PTV) margins (7 mm). A moderate correlation (0.49–0.65) was observed between the surface signal and X-ray position in DIBH. Conclusion: DIBH treatments using thermo-optical SGRT and X-ray IGRT were feasible for breast cancer patients. Stereoscopic X‑ray positioning was successfully verified by standard IGRT techniques. [ABSTRACT FROM AUTHOR]

Real-time tumor-tracking volumetric modulated arc therapy (RT-VMAT) enabling beam-gating based on continuous X-ray tracking of the three-dimensional position of internal markers is relevant for moving tumors. Dose-volume characteristics and treatment time were evaluated in ten consecutive patients who underwent liver stereotactic body radiation therapy with RT-VMAT. Target dose conformity and sparing of the stomach and the intestine were improved comparing RT-VMAT with RT-3D conformal radiotherapy. The mean treatment time for each fraction was less than 10 min. RT-VMAT could be effective, especially for targets located adjacent to organs at risk.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often >2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

Background and purpose: Four-dimensional magnetic resonance imaging (4DMRI) has gained interest as an alternative to the current standard for motion management four-dimensional tomography (4DCT) in abdominal radiotherapy treatment planning (RTP). This review aims to assess the 4DMRI literature in abdomen, focusing on technical considerations and the validity of using 4DMRI for patients within radiotherapy protocols. Materials and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed across the Medline, Embase, Scopus, and Web of Science databases, covering all years up to December 31, 2023. The studies were grouped into two categories: 4DMRI reconstructed from 3DMRI acquisition; and 4DMRI reconstructed from multi-slice 2DMRI acquisition. Results: A total of 39 studies met the inclusion criteria and were analysed to provide key findings. Key findings were 4DMRI had the potential to improve abdominal RTP for patients by providing accurate tumour definition and motion assessment compared to 4DCT. 4DMRI reconstructed from 3DMRI acquisition showed promise as a feasible approach for motion management in abdominal RTP regarding spatial resolution. Currently,the slice thickness achieved on 4DMRI reconstructed from multi-slice 2DMRI acquisitions was unsuitable for clinical purposes. Lastly, the current barriers for clinical implementation of 4DMRI were the limited availability of validated commercial solutions and the lack of larger cohort comparative studies to 4DCT for target delineation and plan optimisation. Conclusion: 4DMRI showed potential improvements in abdominal RTP, but standards and guidelines for the use of 4DMRI in radiotherapy were required to demonstrate clinical benefits.

Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites. However, the optimal radiation dose for long-term local control of adrenal metastases has yet to be determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control. Materials/Methods: After IRB approval, a retrospective data review of patients treated with SBRT for adrenal metastases at a medical center in Israel between 2015 and 2021 was conducted. A biological effective dose was calculated using an alpha beta ratio of 10. Kaplan Meier and Cox regression were calculated using SPSS software to describe the hazard ratio for local control and survival. Results: 83 cases of adrenal SBRT were identified. The average age was 67 (range 42–92 years old). Non-small cell lung cancer was the primary site in 44 % of patients. A total of 70 % of the patients had oligometastatic disease (less than five lesions), and the rest were polymetastatic, responding to systemic therapy with oligo progression in the adrenal. The average gross tumor volume (GTV) was 42 ml. Respiratory control was applied in 88 % of cases; 49.3 % used 4-D/ITV, and 38.5 % used breath-hold or continuous positive airway pressure (CPAP) with free breathing. On multivariable analysis, Dose above 75 Gy (biological effective Dose) (HR = 0.41, p = 0.031), Dose above 8 Gy per fraction (HR = 0.53p = 0.038), and breath-holds or CPAP (HR = 0.65, p = 0.047) were significant for local control. From multivariable analysis, we computed a predicted nomogram curve using seven clinical parameters to evaluate local control odds. Conclusion: In this single institution series reported to date, we found unilateral adrenal SBRT safe, yet bilateral treatment harbors a risk of adrenal insufficiency. Biological effective Dose > 75 Gy (BED), motion management with breath-hold or CPAP, and Dose per fraction > 8 Gy were the enhanced local controls. We propose a nomogram to help in decision-making regarding total Dose and Dose per fraction when treating adrenal SBRT.

Accurately determining tumor regions from stereo fluoroscopic images during radiotherapy is a challenging task. As a result, high-density fiducial markers are implanted around tumors in clinical practice as internal surrogates of the tumor, which leads to associated surgical risks. This study was conducted to achieve lung tumor localization without the use of fiducial markers. We propose training a cascade U-net system to perform color to grayscale conversion, enhancement, bone suppression, and tumor detection to determine the precise tumor region. We generated Digitally Reconstructed Radiographs (DRRs) and tumor labels from 4D planning CT images as training data. An improved maximum projection algorithm and a novel color-to-gray conversion algorithm were proposed to improve the quality of the generated training data. Training a bone suppression model using bone-enhanced and bone-suppressed DRRs enables the bone suppression model to achieve better bone suppression performance. The mean peak signal-to-noise ratios in the test sets of the trained translation and bone suppression models are 39.284 ± 0.034 dB and 37.713 ± 0.724 dB, respectively. The results indicate that our proposed markerless tumor localization method is applicable in seven out of ten cases; in applicable cases, the centroid position error of the tumor detection model is less than 1.13 mm; and the calculated tumor center motion trajectories using the proposed network highly coincide with the motion trajectories of implanted fiducial markers in over 60% of captured groups, providing a promising direction for markerless tumor localization tracking methods.

Objective. Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods. Approach. We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients. Main results. The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3 isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data. Significance. The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating. [ABSTRACT FROM AUTHOR]

Background: Misregistration between CT and PET data can result in mis‐localization and inaccurate quantification of functional uptake in whole body PET/CT imaging. This problem is exacerbated when an abnormal inspiration occurs during the free‐breathing helical CT (FB CT) used for attenuation correction of PET data. In data‐driven gated (DDG) PET, the data selected for reconstruction is typically derived from the end‐expiration (EE) phase of the breathing cycle, making this potential issue worse. Purpose: The objective of this study is to develop a deformable image registration (DIR)‐based respiratory motion model to improve the registration and quantification between misregistered FB CT and PET. Methods: Twenty‐two whole‐body 18F‐FDG PET/CT scans encompassing 48 lesions in misregistered regions were analyzed in this study. End‐inspiration (EI) and EE PET data were derived from −10% to 15% and 30% to 80% of the breathing cycle, respectively. DIR was used to estimate a motion model from the EE to EI phase of the PET data. The model was then used to generate PET images at any phase of up to four times the amplitude of motion between EE and EI for correlation with the misregistered FB CT. Once a matched phase of the FB CT was determined, FB CT was deformed to a pseudo CT at the EE phase (DIR CT). DIR CT was compared with the ground truth DDG CT for AC and localization of the DDG PET. Results: Between DDG PET/FB CT and DDG PET/DIR CT, a significant increase in ∆%SUV was observed (p < 0.01), with median values elevating from 26.7% to 42.4%. This new method was most effective for lesions ≤3 cm proximal to the diaphragm (p < 0.001) but showed decreasing efficacy as the distance increased. When FB CT was severely misregistered with DDG PET (>3 cm), DDG PET/DIR CT outperformed DDG PET/FB CT alone (p < 0.05). Even when patients showed varied breathing patterns during the PET/CT scan, DDG PET/DIR CT still surpassed the efficiency of DDG PET/FB CT (p < 0.01). Though DDG PET/DIR CT couldn't match the performance of the DDG PET/CT ground truth (42.4% vs. 53.6%, p < 0.01), it reached 84% of its quantification, demonstrating good agreement and a strong overall correlation (regression coefficient of 0.94, p < 0.0001). In some cases, anatomical distortion and blurring, and misregistration error were observed in DIR CT, rendering it still unable to correct inaccurate localization near the boundaries of two organs. Conclusions: Based on the motion model derived from gated PET data, DIR CT can significantly improve the quantification and localization of DDG PET. This approach can achieve a performance level of about 84% of the ground truth established by DDG PET/CT. These results show that self‐gated PET and DIR CT may offer an alternative clinical solution to DDG PET and FB CT for quantification without the need for additional cine‐CT imaging. DIR CT was at times inferior to DDG CT due to some distortion and blurring of anatomy and misregistration error. [ABSTRACT FROM AUTHOR]

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose–volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were − 2.9 ± 4.4% (− 16.0 − 1.2%) and − 2.0 ± 2.8% (− 11.2 − 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV. [ABSTRACT FROM AUTHOR]

Purpose: To present a modified calibration method to reduce signal drift due to table sagging in Respiratory Gating for Scanner (RGSC) systems with a wallmounted camera. Materials and Methods: Approximately 70 kg of solid water phantoms were evenly distributed on the CT couch, mimicking the patient's weight. New calibration measurements were performed at 9 points at the combination of three lateral positions, the CT isocenter and ±10 cm laterally from the isocenter, and three longitudinal locations, the CT isocenter and ±30 cm or ±40 cm from the isocenter. The new calibration was tested in two hospitals. Results: Implementing the new weighed calibrationmethod at the extended distance yielded improved results during the DIBH scan, reducing the drift to within 1 from 3 mm. The extended calibration positions exhibited similarly reduced drift in both hospitals, reinforcing the method's robustness and its potential applicability across all centers. Conclusion: This proposed solution aims to minimize the systematic error in radiation delivery for patients undergoing motion management with wallmounted camera RGSC systems, especially in conjunction with a bariatric CT couchtop. [ABSTRACT FROM AUTHOR]

Introduction: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. Methods: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland–Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. Results: The median of translation error between stages of the AlignRT positioning process was (0.03–0.07) cm, and the median of rotation error was (0.20–0.40)°, which were significantly better than those of the Fraxion positioning process (0.09–0.11) cm and (0.60–0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, − 0.07 cm, 0.03 cm, − 0.30°, − 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. Conclusions: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied clinical aspects in central vs. peripheral tumors (n = 78 patients) and applied the internal organ at risk volume (IRV) concept (n = 35 patients) in stereotactic body radiation therapy (SBRT) for centrally located non-small cell lung cancer (NSCLC). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central tumors when compared with peripheral tumors. We here provide evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in cases of higher body mass index. Applying the IRV concept (retrospectively, without new optimization), the normal tissue complication probabilities increased >10% for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment. The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment. [ABSTRACT FROM AUTHOR]

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

PurposeMotion management of tumors within the lung and abdomen is challenging because it requires balancing tissue sparing with accuracy of hitting the target, while considering treatment delivery efficiency. Physicists can play an important role in analyzing four-dimensional computed tomography (4DCT) data to recommend the optimal respiratory gating parameters for a patient. The goal of this work was to develop a standardized procedure for making recommendations regarding gating parameters and planning margins for lung and gastrointestinal stereotactic body radiotherapy (SBRT) treatments. In doing so, we hoped to simplify decision-making and analysis, and provide a tool for troubleshooting complex cases.MethodsFactors that impact gating decisions and planning target volume (PTV) margins were identified. The gating options included gating on exhale with approximately a 50% duty cycle (Gate3070), exhale gating with a reduced duty cycle (Gate4060), and treating for most of respiration, excluding only extreme inhales and exhales (Gate100). A standard operating procedure was developed, as well as a physics consult document to communicate motion management recommendations to other members of the treatment team. This procedure was implemented clinically for 1 year and results are reported below.ResultsIdentified factors that impact motion management included the magnitude of motion observed on 4DCT, the regularity of breathing and quality of 4DCT data, and ability to observe the target on fluoroscopy. These were collated into two decision tables-one specific to lung tumors and another for gastrointestinal tumors-such that a physicist could answer a series of questions to determine the optimal gating and PTV margin. The procedure was used clinically for 252 sites from 213 patients treated with respiratory-gated SBRT and standardized practice across our 12-member physics team.ConclusionImplementation of a standardized procedure for respiratory gating had a positive impact in our clinic, improving efficiency and ease of 4DCT analysis and standardizing gating decision-making amongst physicists.

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Objectives: As an alternative to conventional compression amidst the COVID‐19 pandemic, we developed a contactless motion management strategy. By increasing the patient's breathing rate to induce shallow breathing with the aid of a metronome, our hypothesis is that the motion magnitude of the target may be minimized without physical contact or compression. Methods: Fourteen lung stereotactic body radiation therapy (SBRT) patients treated under fast shallow‐breathing (FSB) were selected for inclusion in this retrospective study. Our proposed method is called shallow kinetics induced by a metronome (SKIM). We induce FSB by setting the beats‐per‐minute (BPM) high (typically in the range of 50–60). This corresponded to a patient breathing rate of 25–30 (breathing) cycles per minute. The magnitude of target motion in 3D under SKIM was evaluated using 4DCT datasets. Comparison with free breathing (FB) 4DCT was also made for a subset for which FB data available. Results: The overall effectiveness of SKIM was evaluated with 18 targets (14 patients). Direct comparison with FB was performed with 12 targets (10 patients). The vector norm mean ± SD value of motion magnitude under SKIM for 18 targets was 8.2 ± 4.1 mm. The mean ± SD metronome BPM was 54.9 ± 4.0 in this group. The vector norm means ± SD values of target motion for FB and SKIM in the 12 target sub‐group were 14.6 ± 8.5 mm and 9.3 ± 3.7 mm, respectively. The mean ± SD metronome BPM for this sub‐group was 56.3 ± 2.5. Conclusion: Compared with FB, SKIM can significantly reduce respiratory motion magnitude of thoracic targets. The difference in maximum motion reduction in the overall vector norm, S‐I, and A‐P directions was significant (p = 0.033, 0.042, 0.011). Our proposed method can be an excellent practical alternative to conventional compression due to its flexibility and ease of implementation. [ABSTRACT FROM AUTHOR]

Background: Dynamic trajectory radiotherapy (DTRT) extends state‐of‐the‐art volumetric modulated arc therapy (VMAT) by dynamic table and collimator rotations during beam‐on. The effects of intrafraction motion during DTRT delivery are unknown, especially regarding the possible interplay between patient and machine motion with additional dynamic axes. Purpose: To experimentally assess the technical feasibility and quantify the mechanical and dosimetric accuracy of respiratory gating during DTRT delivery. Methods: A DTRT and VMAT plan are created for a clinically motivated lung cancer case and delivered to a dosimetric motion phantom (MP) placed on the table of a TrueBeam system using Developer Mode. The MP reproduces four different 3D motion traces. Gating is triggered using an external marker block, placed on the MP. Mechanical accuracy and delivery time of the VMAT and DTRT deliveries with and without gating are extracted from the logfiles. Dosimetric performance is assessed by means of gamma evaluation (3% global/2 mm, 10% threshold). Results: The DTRT and VMAT plans are successfully delivered with and without gating for all motion traces. Mechanical accuracy is similar for all experiments with deviations <0.14° (gantry angle), <0.15° (table angle), <0.09° (collimator angle) and <0.08 mm (MLC leaf positions). For DTRT (VMAT), delivery times are 1.6–2.3 (1.6– 2.5) times longer with than without gating for all motion traces except one, where DTRT (VMAT) delivery is 5.0 (3.6) times longer due to a substantial uncorrected baseline drift affecting only DTRT delivery. Gamma passing rates with (without) gating for DTRT/VMAT were ≥96.7%/98.5% (≤88.3%/84.8%). For one VMAT arc without gating it was 99.6%. Conclusion: Gating is successfully applied during DTRT delivery on a TrueBeam system for the first time. Mechanical accuracy is similar for VMAT and DTRT deliveries with and without gating. Gating substantially improved dosimetric performance for DTRT and VMAT. [ABSTRACT FROM AUTHOR]

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.

PurposeTo suggest PTV margins for liver SBRT with different motion management strategies based on a systematic review and meta-analysis.MethodsIn accordance with Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses (PRISMA), a systematic review in PubMed, Embase and Medline databases was performed for liver tumor position variability. From an initial 533 studies published before October 2020, 36 studies were categorized as 18 free-breathing (FB; npatients = 401), 9 abdominal compression (AC; npatients = 145) and 9 breath-hold (BH; npatients = 126). A meta-analysis was performed on inter- and intra-fraction position variability to report weighted-mean with 95% confidence interval (CI95) in superior-inferior (SI), left-right (LR) and anterior-posterior (AP) directions. Furthermore, weighted-mean ITV margins were computed for FB (nstudies = 15, npatients = 373) and AC (nstudies = 6, npatients = 97) and PTV margins were computed for FB (nstudies = 6, npatients = 95), AC (nstudies = 7, npatients = 106) and BH (nstudies = 8, npatients = 133).ResultsThe FB weighted-mean intra-fraction variability, ITV margins and weighted-standard-deviation in mm were SI-9.7, CI95 = 9.3-10.1, 13.5 ± 4.9; LR-5.4, CI95 = 5.3-5.6, 7.3 ± 7.9; and AP-4.2, CI95 = 4.0-4.4, 6.3 ± 7.6. The inter-fraction-based results were SI-4.7, CI95 = 4.3-5.1, 5.7 ± 1.7; LR-1.4, CI95 = 1.1-1.6, 3.6 ± 2.7; and AP-2.8, CI95 = 2.5-3.1, 4.8 ± 2.1. For AC intra-fraction results in mm were SI-1.8, CI95 = 1.6-2.0, 2.6 ± 1.2; LR-0.7, CI95 = 0.6-0.8, 1.7 ± 1.5; and AP-0.9, CI95 = 0.8-1.0, 1.9 ± 1.7. The inter-fraction results were SI-2.6, CI95 = 2.3-3.0, 5.2 ± 2.9; LR-1.9, CI95 = 1.7-2.1, 4.0 ± 2.2; and AP-2.9, CI95 = 2.5-3.2, 5.8 ± 2.7. For BH the inter-fraction variability, and the weighted-mean PTV margins and weighted-standard-deviation in mm were SI-2.4, CI95 = 2.1-2.7, 5.6 ± 2.9; LR-1.8, CI95 = 1.3-2.2, 5.5 ± 1.7; and AP-1.4; CI95 = 1.2-1.7, 6.1 ± 2.1.ConclusionOur meta-analysis suggests a symmetric weighted-mean PTV margin of 6 mm might be appropriate for BH. For AC and FB, asymmetric PTV margins (weighted-mean margin of 4 mm (AP), 6 mm (SI/LR)) might be appropriate. For FB, if larger (>ITV margin) intra-fraction variability observed, the additional intra- and inter-fraction variability should be accounted in the PTV margin.

4-Dimensional Radiation therapy (4DRT) has been vastly developed in the past two decades. Motion management has become a vital part of high precision radiotherapy, wherein Stereotactic Body Radiation Therapy (SBRT) turns out to be a great boon for treating thoracic and abdominal tumours with confidence. In this review paper, we have analyzed the development of motion management strategies and the advancement of 4DRT. We have discussed the evolution of Internal target volume (ITV), 4D imaging techniques and the problems of breathing motion. In the second part, we have discussed various methods to tackle breathing motion. We also have reviewed the dosimetric aspects of 4D imaging and its clinical implications. In the last section, we have elaborated the 4D radiation therapy and recent advancements and practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Motion of the prostate may adversely affect the outcome of radiotherapy. Online tracking of the prostate during irradiation is technologically feasible but only available at select institutions. It would be beneficial to be able to identify patients at risk of particularly high prostate intrafraction motion with simpler technology. In this paper, we present a larger inner diameter of the lesser pelvis as an anatomical predictor for high prostate intrafraction motion. It can be measured with a single planning CT, which should always be available. Risk patients identified in this way could then be selected for more rigorous online motion management or benefit from increased safety margins. Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT. [ABSTRACT FROM AUTHOR]

Background and purpose: Stereotactic body radiotherapy (SBRT) has emerged as a promising treatment for patients with ventricular tachycardia (VT) who do not respond to standard treatments. However, the management of respiratory motion during treatment remains a challenge. This study aimed to investigate the effect of abdominal compression (AC) on respiratory induced motion in the heart. Materials and methods: A patient cohort of 18 lung cancer patients was utilized, where two four-dimensional computed tomography (4DCT) scans were performed for each patient, one with and one without AC. The patient setup consisted of an AC plate together with a stereotactic body frame. The left coronary artery, the left anterior descending artery, the lateral wall of the left ventricle, the heart apex, the carina, and the right and left diaphragm were delineated in max expiration and max inspiration phases in both 4DCT scans. The center of mass shift from expiration to inspiration phase was determined to assess the AC’s impact on respiratory motion. Results: A significant reduction in motion in the superior-inferior direction was found for all heart structures when AC was used. The median respiratory motion of the heart structures decreased by approximately 1–3 mm with AC in the superior-inferior direction, and approximately 60% of the patients had a motion reduction ≥3 mm in the left ventricle wall. Conclusion: These findings suggest that AC has the potential to improve the motion management of SBRT for VT patients, by reducing the respiratory induced motion in the heart.

Objective. The high speed of cardiorespiratory motion introduces a unique challenge for cardiac stereotactic radio-ablation (STAR) treatments with the MR-linac. Such treatments require tracking myocardial landmarks with a maximum latency of 100 ms, which includes the acquisition of the required data. The aim of this study is to present a new method that allows to track myocardial landmarks from few readouts of MRI data, thereby achieving a latency sufficient for STAR treatments. Approach. We present a tracking framework that requires only few readouts of k-space data as input, which can be acquired at least an order of magnitude faster than MR-images. Combined with the real-time tracking speed of a probabilistic machine learning framework called Gaussian Processes, this allows to track myocardial landmarks with a sufficiently low latency for cardiac STAR guidance, including both the acquisition of required data, and the tracking inference. Main results. The framework is demonstrated in 2D on a motion phantom, and in vivo on volunteers and a ventricular tachycardia (arrhythmia) patient. Moreover, the feasibility of an extension to 3D was demonstrated by in silico 3D experiments with a digital motion phantom. The framework was compared with template matching—a reference, image-based, method—and linear regression methods. Results indicate an order of magnitude lower total latency (<10 ms) for the proposed framework in comparison with alternative methods. The root-mean-square-distances and mean end-point-distance with the reference tracking method was less than 0.8 mm for all experiments, showing excellent (sub-voxel) agreement. Significance. The high accuracy in combination with a total latency of less than 10 ms—including data acquisition and processing—make the proposed method a suitable candidate for tracking during STAR treatments. Additionally, the probabilistic nature of the Gaussian Processes also gives access to real-time prediction uncertainties, which could prove useful for real-time quality assurance during treatments. [ABSTRACT FROM AUTHOR]

Objective. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved. To support the clinical practice based on 4D computed tomography (CT), 4D magnetic resonance imaging (MRI) acquisitions can be exploited. The purpose of this study was to validate a method for virtual 4DCT generation from 4DMRI data for lung cancers on a porcine lung phantom, and to apply it to lung cancer patients in PT. Approach. Deformable image registration was used to register each respiratory phase of the 4DMRI to a reference phase. Then, a static 3DCT was registered to this reference MR image set, and the virtual 4DCT was generated by warping the registered CT according to previously obtained deformation fields. The method was validated on a physical phantom for which a ground truth 4DCT was available and tested on lung tumor patients, treated with gated PT at end-exhale, by comparing the virtual 4DCT with a re-evaluation 4DCT. The geometric and dosimetric evaluation was performed for both proton and carbon ion treatment plans. Main results. The phantom validation exhibited a geometrical accuracy within the maximum resolution of the MRI and mean dose deviations, with respect to the prescription dose, up to 3.2% for target D 95%, with a mean gamma pass rate of 98%. For patients, the virtual and re-evaluation 4DCTs showed good correspondence, with errors on target D 95% up to 2% within the gating window. For one patient, dose variations up to 10% at end-exhale were observed due to relevant inter-fraction anatomo-pathological changes that occurred between the planning and re-evaluation CTs. Significance. Results obtained on phantom data showed that the virtual 4DCT method was accurate, allowing its application on patient data for testing within a clinical scenario. [ABSTRACT FROM AUTHOR]

Background: During recent years FLASH radiotherapy (FLASH‐RT) has shown promising results in radiation oncology, with the potential to spare normal tissue while maintaining the antitumor effects. The high speed of the FLASH‐RT delivery increases the need for fast and precise motion monitoring to avoid underdosing the target. Surface guided radiotherapy (SGRT) uses surface imaging (SI) to render a 3D surface of the patient. SI provides real‐time motion monitoring and has a large scanning field of view, covering off‐isocentric positions. However, SI has so far only been used for human patients with conventional setup and treatment. Purpose: The aim of this study was to investigate the performance of SI as a motion management tool during electron FLASH‐RT of canine cancer patients. Methods: To evaluate the SI system's ability to render surfaces of fur, three fur‐like blankets in white, grey, and black were used to imitate the surface of canine patients and the camera settings were optimized for each blanket. Phantom measurements using the fur blankets were carried out, simulating respiratory motion and sudden shift. Respiratory motion was simulated using the QUASAR Respiratory Motion Phantom with the fur blankets placed on the phantom platform, which moved 10 mm vertically with a simulated respiratory period of 4 s. Sudden motion was simulated with an in‐house developed phantom, consisting of a platform which was moved vertically in a stepwise motion at a chosen frequency. For sudden measurements, 1, 2, 3, 4, 5, 6, 7, and 10 Hz were measured. All measurements were both carried out at the conventional source‐to‐surface distance (SSD) of 100 cm, and in the locally used FLASH‐RT setup at SSD = 70 cm. The capability of the SI system to reproduce the simulated motion and the sampling time were evaluated. As an initial step towards clinical implementation, the feasibility of SI for surface guided FLASH‐RT was evaluated for 11 canine cancer patients. Results: The SI camera was capable of rendering surfaces for all blankets. The deviation between simulated and measured mean peak‐to‐peak breathing amplitude was within 0.6 mm for all blankets. The sampling time was generally higher for the black fur than for the white and grey fur, for the measurement of both respiratory and sudden motion. The SI system could measure sudden motion within 62.5 ms and detect motion with a frequency of 10 Hz. The feasibility study of the canine patients showed that the SI system could be an important tool to ensure patient safety. By using this system we could ensure and document that 10 out of 11 canine patients had a total vector offset from the reference setup position <2 mm immediately before and after irradiation. Conclusions: We have shown that SI can be used for surface guided FLASH‐RT of canine patients. The SI system is currently not fast enough to interrupt a FLASH‐RT beam while irradiating but with the short sampling time sudden motion can be detected. The beam can therefore be held just prior to irradiation, preventing treatment errors such as underdosing the target. [ABSTRACT FROM AUTHOR]

PurposeRadiation dose delivered to targets located near the upper abdomen or thorax are significantly affected by respiratory motion, necessitating large margins, limiting dose escalation. Surrogate motion management devices, such as the Real-time Position Management (RPM™) system (Varian Medical Systems, Palo Alto, CA), are commonly used to improve normal tissue sparing. Alternative to current solutions, we have developed and evaluated the feasibility of a real-time position management system that leverages the motion data from the onboard hardware of Apple iOS devices to provide patients with visual coaching with the potential to improve the reproducibility of breathing as well as improve patient compliance and reduce treatment delivery time.Methods and materialsThe iOS application, coined the Instant Respiratory Feedback (IRF) system, was developed in Swift (Apple Inc., Cupertino, CA) using the Core-Motion library and implemented on an Apple iPhone® devices. Operation requires an iPhone®, a three-dimensional printed arm, and a radiolucent projector screen system for feedback. Direct comparison between IRF, which leverages sensor fusion data from the iPhone®, and RPM™, an optical-based system, was performed on multiple respiratory motion phantoms and volunteers. The IRF system and RPM™ camera tracking marker were placed on the same location allowing for simultaneous data acquisition. The IRF surrogate measurement of displacement was compared to the signal trace acquired using RPM™ with univariate linear regressions and Bland-Altman analysis.ResultsPeriodic motion shows excellent agreement between both systems, and subject motion shows good agreement during regular and irregular breathing motion. Comparison of IRF and RPM™ show very similar signal traces that were significantly related across all phantoms, including those motion with different amplitude and frequency, and subjects' waveforms (all r > 0.9, P

The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment.

Introduction: Cardiac radioablation (CR) is a noninvasive treatment option for patients with refractory ventricular tachycardia (VT) during which high doses of radiation, typically 25 Gy, are delivered to myocardial scar. In this study, we investigate motion from cardiac cycle and evaluate the dosimetric impact in a cohort of patients treated with CR. Methods: This retrospective study included eight patients treated at our institution who had respiratory‐correlated and ECG‐gated 4DCT scans acquired within 2 weeks of CR. Deformable image registration was applied between maximum systole (SYS) and diastole (DIAS) CTs to assess cardiac motion. The average respiratory‐correlated CT (AVGresp) was deformably registered to the average cardiac (AVGcardiac), SYS, and DIAS CTs, and contours were propagated using the deformation vector fields (DVFs). Finally, the original treatment plan was recalculated on the deformed AVGresp CT for dosimetric assessment. Results: Motion magnitudes were measured as the mean (SD) value over the DVFs within each structure. Displacement during the cardiac cycle for all chambers was 1.4 (0.9) mm medially/laterally (ML), 1.6 (1.0) mm anteriorly/posteriorly (AP), and 3.0 (2.8) mm superiorly/inferiorly (SI). Displacement for the 12 distinct clinical target volumes (CTVs) was 1.7 (1.5) mm ML, 2.4 (1.1) mm AP, and 2.1 (1.5) SI. Displacements between the AVGresp and AVGcardiac scans were 4.2 (2.0) mm SI and 5.8 (1.4) mm total. Dose recalculations showed that cardiac motion may impact dosimetry, with dose to 95% of the CTV dropping from 27.0 (1.3) Gy on the AVGresp to 20.5 (7.1) Gy as estimated on the AVGcardiac. Conclusions: Cardiac CTV motion in this patient cohort is on average below 3 mm, location‐dependent, and when not accounted for in treatment planning may impact target coverage. Further study is needed to assess the impact of cardiac motion on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of respiratory motion on the delivered dose in the context of proton pencil beam scanning (PBS) transmission FLASH radiotherapy (FLASH-RT) by simulation and phantom measurements. Approach. An in-house simulation code was employed to perform in silico simulation of 2D dose distributions for clinically relevant proton PBS transmission FLASH-RT treatments. A moving simulation grid was introduced to investigate the impacts of various respiratory motion and treatment delivery parameters on the dynamic PBS dose delivery. A strip-ionization chamber array detector and an IROC motion platform were employed to perform phantom measurements of the 2D dose distribution for treatment fields similar to those used for simulation. Main results. Clinically relevant respiratory motion and treatment delivery parameters resulted in degradation of the delivered dose compared to the static delivery as translation and distortion. Simulation showed that the gamma passing rates (2 mm/2% criterion) and target coverage could drop below 50% and 80%, respectively, for certain scenarios if no mitigation strategy was used. The gamma passing rates and target coverage could be restored to more than 95% and 98%, respectively, for short beams delivered at the maximal inhalation or exhalation phase. The simulation results were qualitatively confirmed in phantom measurements with the motion platform. Significance. Respiratory motion could cause dose quality degradation in a clinically relevant proton PBS transmission FLASH-RT treatment if no mitigation strategy is employed, or if an adequate margin is not given to the target. Besides breath-hold, gated delivery can be an alternative motion management strategy to ensure high consistency of the delivered dose while maintaining minimal dose to the surrounding normal tissues. To the best of our knowledge, this is the first study on motion impacts in the context of proton transmission FLASH radiotherapy. [ABSTRACT FROM AUTHOR]

Background and purpose: Strategies to limit the impact of intra-fraction motion during treatment are common in radiotherapy. Margin recipes, however, are not designed to incorporate these strategies. This work aimed to provide a framework to determine how motion management strategies influence treatment margins. Materials and methods: Two models of intra-fraction motion were considered. In model 1 motion was instantaneous, before treatment starts and in model 2 motion was a continuous drift during treatment. Motion management strategies were modelled by truncating the underlying error distribution at cσ, with σ the standard deviation of the distribution and c a free parameter. Using Monte Carlo simulations, we determined how motion management changed the required margin. The analysis was performed for different number of treatment fractions and different standard deviations of the underlying random and systematic errors. Results: The required margin for a continuous drift was found to be well approximated by an average position of the target at ¾ of the drift. Introducing a truncation at cσ, the relative change in the margin was equal to 0.3c. This result held for both models, was independent of σ or the number of fractions and naturally generalizes to the situation with a residual (systematic) error. Conclusion: Treatment margins can be determined when motion management strategies are applied. Moreover, our analysis can be used to study the potential benefit of different motion management strategies. This allows to discuss and determine the most appropriate strategy for margin reduction.

Background and Purpose: A survey on the patterns of practice of respiratory motion management (MM) was distributed to 111 radiation therapy facilities to inform the development of an end-to-end dosimetry audit including respiratory motion. Materials and methods: The survey (distributed via REDCap) asked facilities to provide information specific to the combinations of MM techniques (breath-hold gating – BHG, internal target volume – ITV, free-breathing gating – FBG, mid-ventilation – MidV, tumour tracking – TT), sites treated (thorax, upper abdomen, lower abdomen), and fractionation regimes (conventional, stereotactic ablative body radiation therapy – SABR) used in their clinic. Results: The survey was completed by 78% of facilities, with 98% of respondents indicating that they used at least one form of MM. The ITV approach was common to all MM-users, used for thoracic treatments by 89% of respondents, and upper and lower abdominal treatments by 38%. BHG was the next most prevalent (41% of MM users), with applications in upper abdominal and thoracic treatment sites (28% vs 25% respectively), but minimal use in the lower abdomen (9%). FBG and TT were utilised sparingly (17%, 7% respectively), and MidV was not selected at all. Conclusions: Two distinct treatment workflows (including use of motion limitation, imaging used for motion assessment, dose calculation, and image guidance procedures) were identified for the ITV and BHG MM techniques, to form the basis of the initial audit. Thoracic SABR with the ITV approach was common to nearly all respondents, while upper abdominal SABR using BHG stood out as more technically challenging. Other MM techniques were sparsely used, but may be considered for future audit development.

Background and Purpose: Magnetic resonance-guided radiotherapy (MRgRT) with real-time intra-fraction tumor motion monitoring allows for high precision Stereotactic Ablative Radiotherapy (SABR). This study aimed to investigate the clinical feasibility, patient satisfaction and delivery accuracy of single-fraction MR-guided SABR in a single day (one-stop-shop, OSS). Methods and Materials: Ten patients with small lung tumors eligible for single fraction treatments were included. The OSS procedure consisted of consultation, treatment simulation, treatment planning and delivery. Following SABR delivery, patients completed a reported experience measure (PREM) questionnaire. Prescribed doses ranged 28–34 Gy. Median GTV was 2.2 cm3 (range 1.3–22.9 cm3). A gating boundary of 3 mm, and PTV margin of 5 mm around the GTV, were used with auto-beam delivery control. Accuracy of SABR delivery was studied by analyzing delivered MR-cines reconstructed from machine log files. Results: All 10 patients completed the OSS procedure in a single day, and all reported satisfaction with the process. Median time for the treatment planning step and the whole procedure were 2.8 h and 6.6 h, respectively. With optimization of the procedure, treatment could be completed in half a day. During beam-on, the 3 mm tracking boundary encompassed between 78.0 and 100 % of the GTV across all patients, with corresponding PTV values being 94.4–100 % (5th-95th percentiles). On average, system-latency for triggering a beam-off event comprised 5.3 % of the delivery time. Latency reduced GTV coverage by an average of −0.3 %. Duty-cycles during treatment delivery ranged from 26.1 to 64.7 %. Conclusions: An OSS procedure with MR-guided SABR for lung cancer led to good patient satisfaction. Gated treatment delivery was highly accurate with little impact of system-latency.

Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient’s abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam’s eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D2% − D98%/D50% ×100%. Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. Materials/Methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonanceguided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a nonadaptive workflow. Two patients received fractionated MRgRT for an ALKrearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing. [ABSTRACT FROM AUTHOR]

Purpose: To assess the resulting dosimetry characteristics of simulation and planning techniques for proton stereotactic body radiation therapy (SBRT) of primary and secondary liver tumors. Methods: Consecutive patients treated under volumetric daily image guidance with liver proton SBRT between September 2019 and March 2022 at Emory Proton Therapy Center were included in this study. Prescriptions ranged from 40 Gy to 60 Gy in 3- or 5-fraction regimens, and motion management techniques were used when target motion exceeded 5 mm. 4D robust optimization was used when necessary. Dosimetry evaluation was conducted for ITV V100, D99, Dmax, and liver-ITV mean dose and D700cc. Statistical analysis was performed using independent-samples Mann-Whitney U tests. Results: Thirty-six tumors from 29 patients were treated. Proton therapy for primary and secondary liver tumors using motion management techniques and robust optimization resulted in high target coverage and low doses to critical organs. The median ITV V100% was 100.0%, and the median ITV D99% was 111.3%. The median liver-ITV mean dose and D700cc were 499 cGy and 5.7 cGy, respectively. The median conformity index (CI) was 1.03, and the median R50 was 2.56. Except for ITV D99% (primary 118.1% vs. secondary 107.2%, p = 0.005), there were no significant differences in age, ITV volume, ITV V100%, ITV maximum dose, liver-ITV mean dose, or D700cc between primary and secondary tumor groups. Conclusion: The study demonstrated that proton therapy with motion management techniques and robust optimization achieves excellent target coverage with low normal liver doses for primary and secondary liver tumors. The results showed high target coverage, high conformality, and low doses to the liver. [ABSTRACT FROM AUTHOR]

This study presents the clinical experiences of the New York Proton Center in employing proton pencil beam scanning (PBS) for the treatment of lung stereotactic body radiation therapy. It encompasses a comprehensive examination of multiple facets, including patient simulation, delineation of target volumes and organs at risk, treatment planning, plan evaluation, quality assurance, and motion management strategies. By sharing the approaches of the New York Proton Center and providing recommendations across simulation, treatment planning, and treatment delivery, it is anticipated that the valuable experience will be provided to a broader proton therapy community, serving as a useful reference for future clinical practice and research endeavors in the field of stereotactic body proton therapy for lung tumors. [ABSTRACT FROM AUTHOR]

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 Tres$T_{res}$. Prostate intrafractional rotational motion Runcorr$R_{uncorr}$ was recorded but not corrected. The dose differences from the planned dose due to Tres$T_{res}$ + Runcorr$R_{uncorr}$, ΔD(Tres$T_{res}$ + Runcorr$R_{uncorr}$) and due to Tres$T_{res}$ alone, ΔD(Tres$T_{res}$), were then determined for CTV D98, PTV D95, bladder V6Gy, and rectum V6Gy. The residual dose error due to uncorrected rotation, Runcorr$R_{uncorr}$ was then quantified: ΔDResidual$\Delta D_{Residual}$ = ΔD(Tres$T_{res}$ + Runcorr$R_{uncorr}$) ‐ ΔD(Tres${T}_{\textit{res}}$). Results: Fractional data analysis shows that the dose differences from the plan (both ΔD(Tres$T_{res}$ + Runcorr$R_{uncorr}$) and ΔD(Tres$T_{res}$)) for CTV D98 was less than 5% in all treatment fractions. ΔD(Tres$T_{res}$ + Runcorr$R_{uncorr}$) 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, Runcorr$R_{uncorr}$ induced residual dose error, ΔDResidual$\Delta D_{Residual}$, 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(Tres$T_{res}$ + Runcorr$R_{uncorr}$) and ∑D(Tres$T_{res}$), 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. [ABSTRACT FROM AUTHOR]