Objective:. In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for a planning... Show moreObjective:. In online adaptive radiotherapy a new plan is generated every fraction based on the organ and clinical target volume (CTV) delineations of that fraction. This allows for a planning target volume margin that does not need to be constant over the whole course of treatment, as is the case in conventional radiotherapy. This work aims to introduce an approach to update the margins each fraction based on the per-patient treatment history and explore the potential benefits of such adaptive margins. Approach: We introduce a novel methodology to implement adaptive margins, isotropic and anisotropic, during a treatment course based on the accumulated dose to the CTV. We then simulate treatment histories for treatments delivered in up to 20 fractions using various choices for the standard deviations of the systematic and random errors and homogeneous and inhomogeneous dose distributions. The treatment-averaged adaptive margin was compared to standard constant margins. The change in the minimum dose delivered to the CTV was compared on a patient and a population level. All simulations were performed within the van Herk approach and its known limitations. Main results: The population mean treatment-averaged margins are down to 70% and 55% of the corresponding necessary constant margins for the isotropic and anisotropic approach. The reduction increases with longer fractionation schemes and an inhomogeneous target dose distribution. Most of the benefit can be attributed to the elimination of the effective systematic error over the course of treatment. Interpatient differences in treatment-averaged margins were largest for the isotropic margins. For the 10% of patients that would receive a lower than prescribed dose to the CTV this minimum dose to the CTV is increased using the adaptive margin approaches. Significance: Adaptive margins can allow to reduce margins in most patients without compromising patients with greater than average target motion. Show less
Janssen, T.M.; Heide, U.A. van der; Remeijer, P.; Sonke, J.J.; Bijl, E. van der 2022
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... Show moreBackground 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. Show less
Kensen, C.M.; Janssen, T.M.; Betgen, A.; Wiersema, L.; Peters, F.P.; Remeijer, P.; ... ; Heide, U.A. van der 2022
Purpose: To determine PTV margins for intrafraction motion in MRI-guided online adaptive radiotherapy for rectal cancer and the potential benefit of performing a 2nd adaptation prior to irradiation... Show morePurpose: To determine PTV margins for intrafraction motion in MRI-guided online adaptive radiotherapy for rectal cancer and the potential benefit of performing a 2nd adaptation prior to irradiation. Methods: Thirty patients with rectal cancer received radiotherapy on a 1.5 T MR-Linac. On T2-weighted images for adaptation (MRIadapt), verification prior to (MRIver) and after irradiation (MRIpost) of 5 treatment fractions per patient, the primary tumor GTV (GTV(prim)) and mesorectum CTV (CTVmeso) were delineated. The structures on MRIadapt were expanded to corresponding PTVs. We determined the required expansion margins such that on average over 5 fractions, 98% of CTVmeso and 95% of GTV(prim) on MRIpost was covered in 90% of the patients. Furthermore, we studied the benefit of an additional adaptation, just prior to irradiation, by evaluating the coverage between the structures on MRIver and MRIpost. A threshold to assess the need for a secondary adaptation was determined by considering the overlap between MRIadapt and MRIver. Results: PTV margins for intrafraction motion without 2nd adaptation were 6.4 mm in the anterior direction and 4.0 mm in all other directions for CTVmeso and 5.0 mm isotropically for GTV(prim). A 2nd adaptation, applied for all fractions where the motion between MRIadapt and MRIver exceeded 1 mm (36% of the fractions) would result in a reduction of the PTVmeso margin to 3.2 mm/2.0 mm. For PTVprim a margin reduction to 3.5 mm is feasible when a 2nd adaptation is performed in fractions where the motion exceeded 4 mm (17% of the fractions). Conclusion: We studied the potential benefit of intrafraction motion monitoring and a 2nd adaptation to reduce PTV margins in online adaptive MRIgRT in rectal cancer. Performing 2nd adaptations immediately after online replanning when motion exceeded 1 mm and 4 mm for CTVmeso and GTV(prim) respectively, could result in a 30-50% margin reduction with limited reduction of dose to the bowel. Show less
Couwenberg, A.; Heide, U. van der; Janssen, T.; Triest, B. van; Remeijer, P.; Marijnen, C.; ... ; Nowee, M. 2022
The master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation...Show moreThe master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation oncology. A master protocol to study feasibility of techniques/software for MR-guided adaptive radiotherapy with the MR-Linac is described and discussed. Show less
Purpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy... Show morePurpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and Methods: Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations.Results: Fifty-six patients with tumors located in the proximal (n=1), mid (n=7), or distal esophagus (n=25) or at the gastroesophageal junction (n=23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins.Conclusions: Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy. (C) 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Show less
Purpose: In radiation therapy, head and neck (H&N) supports and thermoplastic masks are used to reproduce the setup of patients for H&N treatment. Individualized supports that include the... Show morePurpose: In radiation therapy, head and neck (H&N) supports and thermoplastic masks are used to reproduce the setup of patients for H&N treatment. Individualized supports that include the shoulders may improve the immobilization of the upper thorax region. The purpose of this study was to compare the local misalignment of the supraclavicular region using a vacuum cushion H&N support to a more simple in-house modified, clinically standard H&N support.Methods and materials: Two groups of 15 patients were evaluated: the first group of patients was positioned using a vacuum cushion as an individual head support and the second group with a modified Posifix headrest (MPH). A total of 316 cone beam computed tomography (CBCTs; similar to 10 scans per patient) were evaluated using a multiple region of interest registration protocol. Local setup errors were measured using chamfer matching on the CBCT scan to the planning CT scan for 9 bony structures (cervical vertebrae 1, 3, 5, and 7 [C7], lower jaw, hyoid bone, larynx, skull, and jugular notch). In this study, we compared the local residual misalignments of the bony structures and in particular those of the jugular notch and C7 as surrogates of the shoulders and thorax region. The workload was qualitatively evaluated on the basis of open interviews.Results: The significant differences in group mean, systematic error, and random error of the local residual misalignments between the 2 groups for jugular notch and C7 were equal or smaller than 0.5 mm and 0.1 degrees, and for the other 7 bony structures were equal to or smaller than 0.6 mm and 1.2 degrees (larynx). There were no large differences in workload.Conclusions: No clinically relevant differences were found between a modified Posifix headrest and an individual vacuum cushion for H&N cancer patients in local posture change at the level of the clavicle and upper thorax. (C) 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Show less
Topolnjak, R.; Ruiter, P. de; Remeijer, P.; Vliet-Vroegindeweij, C. van; Rasch, C.; Sonke, J.J. 2011
Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam... Show morePurpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans.Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Sigma] and random [sigma]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity.Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Sigma(left-right) = 1.2, sigma(left-right) = 1.0; Sigma(cranial-caudal) = 1.3, sigma(cranial-caudal) = 1.2; and Sigma(anterior-posterior) = 0.7, sigma(anterior-posterior) = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan).Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors. (c) 2011 Elsevier Inc. Show less
Topolnjak, R.; Sonke, J.J.; Nijkamp, J.; Rasch, C.; Minkema, D.; Remeijer, P.; Vliet-Vroegindeweij, C. van 2010
Purpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients.Methods and... Show morePurpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients.Methods and Materials: Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis.Results: Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Sigma(U) = 1.4 mm, Sigma(V) = 1.7 mm, and sigma(U) = 2.6 mm, sigma(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Sigma(U) = 2.2mm, Sigma(V) = 3.3 mm, and sigma(U) = 2.9 mm, sigma(V) = 2.9 mm.Conclusion: EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly. (C) 2010 Elsevier Inc. Show less
Beek, S. van; Kranen, S. van; Mencarelli, A.; Remeijer, P.; Rasch, C.; Herk, M. van; Sonke, J.J. 2010
Purpose: To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients... Show morePurpose: To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients.Materials and methods: 12-13 3D rectangular-shaped ROIs were automatically placed around bony structures on the planning CT scans (n = 50 patients) which were individually registered to subsequent CBCT scans. mROI registration was used to quantify global and local setup errors. The time required to perform the mROI registration was compared with that of a previously used single-ROI method. The number of scans with residual local setup error exceeding 5 mm/5 degrees (warnings) was scored together with the frequency ROIs exceeding these limits for three or more consecutive imaging fractions (systematic errors).Results: In 40% of the CBCT scans, one or more ROI-registrations exceeded the 5 mm/5 degrees. Most warnings were seen in ROI "hyoid", 31% of the rotation warnings and 14% of the translation warnings. Systematic errors lead to 52 consults of the treating physician. The preparation and registration time was similar for both registration methods.Conclusions: The mROI registration method is easy to use with little extra workload, provides additional information on local setup errors, and helps to select patients for re-planning. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 94 (2010) 213-217 Show less
