Geometric distortions in clinical MRI sequences for radiotherapy: insights gained from a multicenter investigation.

BACKGROUND: As magnetic resonance imaging (MRI) becomes increasingly integrated into radiotherapy (RT) for enhanced treatment planning and adaptation, the inherent geometric distortion in acquired MR images pose a potential challenge to treatment accuracy. This study aimed to evaluate the geometric distortion levels in the clinical MRI protocols used across Danish RT centers and discuss influence of specific sequence parameters. Based on the variety in geometric performance across centers, we assess if harmonization of MRI sequences is a relevant measure. MATERIALS AND METHODS: Nine centers participated with 12 MRI scanners and MRI-Linacs (MRL). Using a travelling phantom approach, a reference MRI sequence was used to assess variation in baseline distortion level between scanners. The phantom was also scanned with local clinical MRI sequences for brain, head/neck (H/N), abdomen, and pelvis. The influence of echo time, receiver bandwidth, image weighting, and 2D/3D acquisition was investigated. RESULTS: We found a large variation in geometric accuracy across 93 clinical sequences examined, exceeding the baseline variation found between MRI scanners (σ = 0.22 mm), except for abdominal sequences where the variation was lower. Brain and abdominal sequences showed lowest distortion levels ([0.22, 2.26] mm), and a large variation in performance was found for H/N and pelvic sequences ([0.19, 4.07] mm). Post hoc analyses revealed that distortion levels decreased with increasing bandwidth and a less clear increase in distortion levels with increasing echo time. 3D MRI sequences had lower distortion levels than 2D (median of 1.10 and 2.10 mm, respectively), and in DWI sequences, the echo-planar imaging read-out resulted in highest distortion levels. CONCLUSION: There is a large variation in the geometric distortion levels of clinical MRI sequences across Danish RT centers, and between anatomical sites. The large variation observed makes harmonization of MRI sequences across institutions and adoption of practices from well-performing anatomical sites, a relevant measure within RT.

Accuracy of automatic structure propagation for daily magnetic resonance image-guided head and neck radiotherapy.

BACKGROUND AND PURPOSE: Deformable image registration (DIR) and contour propagation are used in daily online adaptation for hybrid MRI linac (MRL) treatments. The accuracy of the propagated contours may vary depending on the chosen workflow (WF), affecting the amount of required manual corrections. This study investigated the impact of three different WFs of contour propagations produced by a clinical treatment planning system for a high-field MRL on head and neck cancer patients. METHODS: Seventeen patients referred for curative radiotherapy for oropharyngeal cancer underwent standard CT-based dose planning and MR scans in the treatment position for planning (pMR), and at the 10th (MR10), 20th (MR20) and 30th (MR30) fraction (±2). The primary tumour, a metastatic lymph node and 8 organs at risk were manually delineated on each set of T2 weighted images. Delineations were repeated one month later on the pMR by the same observer to determine the intra-observer variation (IOV). Three WFs were used to deform images in the treatment planning system for the high-field MRL: In WF1, only the planning image and contours were used as a reference for DIR and propagation to MR10,20,30. The most recently acquired image set prior to the daily images was deformed and uncorrected (WF2) versus manually corrected (WF3) structures propagated to the session image. Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD) were calculated for each structure in each model. RESULTS: Population median DSC, MSD and HD for WF1 and WF3 were similar and slightly better than for WF2. WF3 provided higher accuracy than WF1 for structures that are likely to shrink. All DIR workflows were less accurate than the IOV. CONCLUSIONS: WF1 and WF3 provide higher accuracy in structure propagation than WF2. Manual revision and correction of propagated structures are required for all evaluated workflows.

First clinical experiences with a high field 1.5 T MR linac.

Purpose: A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy. Method and materials: Two different WF were used dependent on the clinical situation of the day; Adapt To Position WF (ATP) where the reference plan position is adjusted rigidly to match the position of the targets and the OARs, and Adapt To Shape WF (ATS), where a new plan is created to match the anatomy of the day, using deformable image registration. Both WFs included three 3D MRI scans for plan adaptation, verification before beam on, and validation during IMRT delivery. Patient compliance and WF timings were recorded. Accuracy in dose delivery was assessed using a cylindrical diode phantom. Results: Nineteen patients have completed their treatment receiving a total of 176 fractions. Cases vary from prostate treatments (60Gy/20F) to SBRT treatments of lymph nodes (45 Gy/3F) and castration by ovarian irradiation (15 Gy/3F). The median session time (patient in to patient out) for 127 ATPs was 26 (21-78) min, four fractions lasted more than 45 min due to additional plan adaptation. For the 49 ATSs a median time of 12 (1-24) min was used for contouring resulting in a total median session time of 42 (29-91) min. Three SBRT fractions lasted more than an hour. The time on the MRL couch was well tolerated by the patients. The median gamma pass rate (2 mm,2% global max) for the adapted plans was 99.2 (93.4-100)%, showing good agreement between planned and delivered dose. Conclusion: MRL treatments, including daily MRIs, plan adaptation, and accurate dose delivery, are possible within a clinically acceptable timeframe and well tolerated by the patients.

Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer.

BACKGROUND: The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients. MATERIAL AND METHODS: Thirty-two consecutive inoperable patients with esophageal cancer originally treated with manually (MA) generated volumetric modulated arc therapy (VMAT) plans were retrospectively replanned using an auto-planning engine. All plans were optimized with one full 6MV VMAT arc giving 60 Gy to the primary target and 50 Gy to the elective target. The planning techniques were blinded before clinical evaluation by three specialized oncologists. To supplement the clinical evaluation, the optimization time for the AU plan was recorded along with DVH parameters for all plans. RESULTS: Upon clinical evaluation, the AU plan was preferred for 31/32 patients, and for one patient, there was no difference in the plans. In terms of DVH parameters, similar target coverage was obtained between the two planning methods. The mean dose for the spinal cord increased by 1.8 Gy using AU (p = .002), whereas the mean lung dose decreased by 1.9 Gy (p < .001). The AU plans were more modulated as seen by the increase of 12% in mean MUs (p = .001). The median optimization time for AU plans was 117 min. CONCLUSIONS: The AU plans were in general preferred and showed a lower mean dose to the lungs. The automation of the planning process generated esophageal cancer treatment plans quickly and with high quality.

Adaptive MRI-guided stereotactic body radiation therapy for locally advanced pancreatic cancer - A phase II study.

PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). METHODS: This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. RESULTS: Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. CONCLUSION: This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.

A multi-institutional comparison of retrospective deformable dose accumulation for online adaptive magnetic resonance-guided radiotherapy.

Background and Purpose: Application of different deformable dose accumulation (DDA) solutions makes institutional comparisons after online-adaptive magnetic resonance-guided radiotherapy (OA-MRgRT) challenging. The aim of this multi-institutional study was to analyze accuracy and agreement of DDA-implementations in OA-MRgRT. Material and Methods: One gold standard (GS) case deformed with a biomechanical-model and five clinical cases consisting of prostate (2x), cervix, liver, and lymph node cancer, treated with OA-MRgRT, were analyzed. Six centers conducted DDA using institutional implementations. Deformable image registration (DIR) and DDA results were compared using the contour metrics Dice Similarity Coefficient (DSC), surface-DSC, Hausdorff-distance (HD95%), and accumulated dose-volume histograms (DVHs) analyzed via intraclass correlation coefficient (ICC) and clinical dosimetric criteria (CDC). Results: For the GS, median DDA errors ranged from 0.0 to 2.8 Gy across contours and implementations. DIR of clinical cases resulted in DSC > 0.8 for up to 81.3% of contours and a variability of surface-DSC values depending on the implementation. Maximum HD95%=73.3 mm was found for duodenum in the liver case. Although DVH ICC > 0.90 was found after DDA for all but two contours, relevant absolute CDC differences were observed in clinical cases: Prostate I/II showed maximum differences in bladder V28Gy (10.2/7.6%), while for cervix, liver, and lymph node the highest differences were found for rectum D2cm3 (2.8 Gy), duodenum Dmax (7.1 Gy), and rectum D0.5cm3 (4.6 Gy). Conclusion: Overall, high agreement was found between the different DIR and DDA implementations. Case- and algorithm-dependent differences were observed, leading to potentially clinically relevant results. Larger studies are needed to define future DDA-guidelines.

MR-guided stereotactic radiotherapy of infra-diaphragmatic oligometastases: Evaluation of toxicity and dosimetric parameters.

BACKGROUND AND PURPOSE: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE). MATERIALS AND METHODS: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model. RESULTS: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D0.1cc, D1cc, and D20cc. CONCLUSION: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D0.1cc, D1cc, and D20cc were associated with grade ≥ 2 GI toxicity.

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 - 53.7 Gy for case 1, 22.6 - 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9-53.6 Gy for case 1, 33.9-36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2-50.9 Gy for case 1, 33.5-36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems.

Radiopaque marker motion during pre-treatment CBCT as a predictor of intra-fractional prostate movement.

UNLABELLED: The intra-fractional movement of the prostate constitutes a hindrance for the reduction of the planning target volume margin for prostate cancer patients. Monitoring the movement of the prostate during treatment is a promising but in most centres not feasible solution. However, the projection images of the pre-treatment cone-beam computed tomography (CBCT) provide information about the motion of the target immediately preceding the treatment. This motion information can be extracted from any standard CBCT scan which is available in many institutions. In this study we measure the motion of the prostate during the pre-treatment CBCT and investigate whether this motion is correlated with the intra-fractional movement of the prostate. MATERIAL AND METHODS: Pre- and post-treatment CBCT scans were made during a number of the fractions (average 11 range 8-12) for 13 prostate cancer patients during the radiation treatment course. The displacement of the post-treatment CBCT scans relative to the pre-treatment position was used to assess the intra-fractional motion. Automated image analysis was used to track the 2D position of radiopaque markers in the projection images of the scans. The most probable 3D trajectory of the markers during the CBCT scan was estimated based on a probability density function which was established for each individual scan. RESULTS: The accuracy of the tracking algorithm was found satisfactory and the motion of the markers during the CBCT scans was successfully extracted from the projection images. This motion was generally small and uncorrelated with the subsequent intra-fractional movement of the prostate. The correlation coefficients were 20.05, 0.07, and 20.05 in the LR, AP, and CC direction, respectively. CONCLUSION: It is tempting to exploit the pre-treatment CBCT to predict the intra-fractional movement of the prostate but, unfortunately, we have found no correlation between the intra-fractional movement and the motion of the prostate immediately prior to treatment.

Patient-specific scatter correction in clinical cone beam computed tomography imaging made possible by the combination of Monte Carlo simulations and a ray tracing algorithm.

PURPOSE: Cone beam computed tomography (CBCT) image quality is limited by scattered photons. Monte Carlo (MC) simulations provide the ability of predicting the patient-specific scatter contamination in clinical CBCT imaging. Lengthy simulations prevent MC-based scatter correction from being fully implemented in a clinical setting. This study investigates the combination of using fast MC simulations to predict scatter distributions with a ray tracing algorithm to allow calibration between simulated and clinical CBCT images. MATERIAL AND METHODS: An EGSnrc-based user code (egs_cbct), was used to perform MC simulations of an Elekta XVI CBCT imaging system. A 60 keV x-ray source was used, and air kerma scored at the detector plane. Several variance reduction techniques (VRTs) were used to increase the scatter calculation efficiency. Three patient phantoms based on CT scans were simulated, namely a brain, a thorax and a pelvis scan. A ray tracing algorithm was used to calculate the detector signal due to primary photons. A total of 288 projections were simulated, one for each thread on the computer cluster used for the investigation. RESULTS: Scatter distributions for the brain, thorax and pelvis scan were simulated within 2% statistical uncertainty in two hours per scan. Within the same time, the ray tracing algorithm provided the primary signal for each of the projections. Thus, all the data needed for MC-based scatter correction in clinical CBCT imaging was obtained within two hours per patient, using a full simulation of the clinical CBCT geometry. CONCLUSIONS: This study shows that use of MC-based scatter corrections in CBCT imaging has a great potential to improve CBCT image quality. By use of powerful VRTs to predict scatter distributions and a ray tracing algorithm to calculate the primary signal, it is possible to obtain the necessary data for patient specific MC scatter correction within two hours per patient.

Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma-A Critical Review of Randomised Trials.

Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment in patients with both locally advanced and metastatic pancreatic cancer. In contrast, the use of radiotherapy has no clear defined role in the treatment of these patients. With the evolving imaging and radiation techniques, radiation could become a plausible intervention. In this review, we give an overview over the available data regarding radiotherapy, chemoradiation, and stereotactic body radiation therapy. We performed a systematic search of Embase and the PubMed database, focusing on studies involving locally advanced pancreatic cancer (or non-resectable pancreatic cancer) and radiotherapy without any limitation for the time of publication. We included randomised controlled trials involving patients with locally advanced pancreatic cancer, including radiotherapy, chemoradiation, or stereotactic body radiation therapy. The included articles represented mainly small patient groups and had a high heterogeneity regarding radiation delivery and modality. This review presents conflicting results concerning the addition of radiation and modality in the treatment regimen. Further research is needed to improve outcomes and define the role of radiation therapy in pancreatic cancer.

Impact of abdominal compression on intra-fractional motion and delivered dose in magnetic resonance image-guided adaptive radiation ablation of adrenal gland metastases.

PURPOSE: The current study investigated the impact of abdominal compression on motion and the delivered dose during non-gated, magnetic resonance image (MRI)-guided radiation ablation of adrenal gland metastases. METHODS: Thirty-one patients with adrenal gland metastases treated to 45-60 Gy in 3-8 fractions on a 1.5 T MRI-linac were included in the study. The patients were breathing freely (n = 14) or with motion restricted by using an abdominal compression belt (n = 17). The time-resolved position of the target in online 2D cine MR images acquired during treatment was assessed and used to estimate the dose delivered to the GTV and abutting luminal organs at risk (OAR). RESULTS: The median (range) 3D root-mean-square target position error was significantly higher in patients treated without a compression belt [2.9 (1.9-5.6) mm] compared to patients using the belt [2.1 (1.2-3.5) mm] (P < 0.01). The median (range) GTV V95% was significantly reduced from planned 98.6 (65.9-100) % to delivered 96.5 (64.5-99.9) % due to motion (P < 0.01). Most prominent dose reductions were found in patients showing either large target drift or respiration motion and were mainly treated without abdominal compression. Motion did not lead to an increased number of constraint violations for luminal OAR. CONCLUSIONS: Acceptable target coverage and dose to OAR was observed in the vast majority of patients despite intra-fractional motion during adaptive MRI-guided radiation ablation. The use of abdominal compression significantly reduced the target position error and prevented the most prominent target coverage degradations and is, therefore, recommended as motion management at MRI-linacs.

An open-source nnU-net algorithm for automatic segmentation of MRI scans in the male pelvis for adaptive radiotherapy.

Background: Adaptive MRI-guided radiotherapy (MRIgRT) requires accurate and efficient segmentation of organs and targets on MRI scans. Manual segmentation is time-consuming and variable, while deformable image registration (DIR)-based contour propagation may not account for large anatomical changes. Therefore, we developed and evaluated an automatic segmentation method using the nnU-net framework. Methods: The network was trained on 38 patients (76 scans) with localized prostate cancer and tested on 30 patients (60 scans) with localized prostate, metastatic prostate, or bladder cancer treated at a 1.5 T MRI-linac at our institution. The performance of the network was compared with the current clinical workflow based on DIR. The segmentation accuracy was evaluated using the Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) metrics. Results: The trained network successfully segmented all 600 structures in the test set. High similarity was obtained for most structures, with 90% of the contours having a DSC above 0.9 and 86% having an MSD below 1 mm. The largest discrepancies were found in the sigmoid and colon structures. Stratified analysis on cancer type showed that the best performance was seen in the same type of patients that the model was trained on (localized prostate). Especially in patients with bladder cancer, the performance was lower for the bladder and the surrounding organs. A complete automatic delineation workflow took approximately 1 minute. Compared with contour transfer based on the clinically used DIR algorithm, the nnU-net performed statistically better across all organs, with the most significant gain in using the nnU-net seen for organs subject to more considerable volumetric changes due to variation in the filling of the rectum, bladder, bowel, and sigmoid. Conclusion: We successfully trained and tested a network for automatically segmenting organs and targets for MRIgRT in the male pelvis region. Good test results were seen for the trained nnU-net, with test results outperforming the current clinical practice using DIR-based contour propagation at the 1.5 T MRI-linac. The trained network is sufficiently fast and accurate for clinical use in an online setting for MRIgRT. The model is provided as open-source.

Correlation between the ripple phase and stripe domains in membranes.

We investigate the relationship between stripe domains and the ripple phase in membranes. These have previously been observed separately without being linked explicitly. Past results have demonstrated that solid and ripple phases exhibit rich textural patterns related to the orientational order of tilted lipids and the orientation of ripple corrugations. Here we reveal a highly complex network pattern of ripple and solid domains in DLPC, DPPC bilayers with structures covering length scales from 10 nm to 100 µm. Using spincoated double supported membranes we investigate domains by correlated AFM and fluorescence microscopy. Cooling experiments demonstrate the mode of nucleation and growth of stripe domains enriched in the fluorescent probe. Concurrent AFM imaging reveals that these stripe domains have a one-to-one correspondence with a rippled morphology running parallel to the stripe direction. Both thin and thick stripe domains are observed having ripple periods of 13.5±0.2 nm and 27.4±0.6 nm respectively. These are equivalent to previously observed asymmetric/equilibrium and symmetric/metastable ripple phases, respectively. Thin stripes grow from small solid domains and grow predominantly in length with a speed of ~3 times that of the thick stripes. Thick stripes grow by templating on the sides of thinner stripes or can emerge directly from the fluid phase. Bending and branching angles of stripes are in accordance with an underlying six fold lattice. We discuss mechanisms for the nucleation and growth of ripples and discuss a generic phase diagram that may partly rationalize the coexistence of metastable and stable phases.

Plan quality in radiotherapy treatment planning - Review of the factors and challenges.

A high-quality treatment plan aims to best achieve the clinical prescription, balancing high target dose to maximise tumour control against sufficiently low organ-at-risk dose for acceptably low toxicity. Treatment planning (TP) includes multiple steps from simulation/imaging and segmentation to technical plan production and reporting. Consistent quality across this process requires close collaboration and communication between clinical and technical experts, to clearly understand clinical requirements and priorities and also practical uncertainties, limitations and compromises. TP quality depends on many aspects, starting from commissioning and quality management of the treatment planning system (TPS), including its measured input data and detailed understanding of TPS models and limitations. It requires rigorous quality assurance of the whole planning process and it links to plan deliverability, assessable by measurement-based verification. This review highlights some factors influencing plan quality, for consideration for optimal plan construction and hence optimal outcomes for each patient. It also indicates some challenges, sources of difference and current developments. The topics considered include: the evolution of TP techniques; dose prescription issues; tools and methods to evaluate plan quality; and some aspects of practical TP. The understanding of what constitutes a high-quality treatment plan continues to evolve with new techniques, delivery methods and related evidence-based science. This review summarises the current position, noting developments in the concept and the need for further robust tools to help achieve it.

The effect of respiration-induced target motion on 3D magnetic resonance images used to guide radiotherapy.

Background and purpose: 3D Magnetic Resonance Imaging (MRI) is used in radiation therapy for reference planning and, lately, for adaptive treatments on MR accelerators. This study aimed to investigate the impact of different types of respiratory motion on the apparent target position and extent in such scans. Materials and methods: An MRI motion phantom with a 30 mm diameter target was used to simulate cranial-caudal (CC) motion and imaged at an MR-Linac using a standard clinically released 3D T2w sequence. Scans were acquired for each combination of functions (sin(t), sin4(t) and sin12(t)), peak-to-peak amplitudes (5, 10, 15 and 20 mm), and periods (4, 5 and 6 s). Furthermore, respiration CC motion patterns from two patients were used. Motion functions were shifted such that the time average target position would match a static reference scan at 0-position. The target was automatically identified in coronal and sagittal images using k-means clustering. The mean position and area of the target were calculated and compared to the reference scan. Results: Artefacts increased with amplitude and depended on the motion type. Sin(t) and sin4(t) oscillations resulted in a blurring of the target, which led to an increased target area, while sin12(t) motion did not show significant changes in the target area. However, for the sin12(t) motion, the offset in apparent position was prominent, while that was not the case for the sin(t) and sin4(t) motion. The patient respiration motion profiles showed similar trends. Conclusions: In 3D MRI, target motion can change apparent tumour extent and apparent position. The changes increase with motion amplitude and depend on the motion type.

Causal relation between heart irradiation and survival of lung cancer patients after radiotherapy.

INTRODUCTION: In a recent study, setup uncertainties in the direction of the heart were shown to impact the overall survival of non-small cell lung cancer (NSCLC) patients after radiotherapy, indicating the causal effect between heart irradiation and survival. The current study aims to externally evaluate this observation within a patient cohort treated using daily IGRT. METHOD: NSCLC patients with locally-advanced disease and daily CBCT were included. For all treatment fractions, the distance between the isocenter and the heart was evaluated based on the clinical setup registrations. The variation in heart position between planning and treatment (DeltaDistance) was estimated from these registrations. The possible impact of DeltaDistance on survival was analysed by a multivariable Cox model of overall survival, allowing for a time-dependent impact of DeltaDistance to allow for toxicity latency. RESULTS: Daily CBCT information was available for 489 patients at Odense University Hospital. The primary Cox model contained GTV volume, patient age, performance status, and DeltaDistance. DeltaDistance significantly impacted overall survival approximately 50 months after radiotherapy. Subanalyses indicated that the observed effect is mainly present among the patients with the least clinical risk factors. CONCLUSION: Our results confirm the impact of setup variations in the direction of the heart on the survival of NSCLC patients, even within a cohort using daily CBCT setup guidance. This result indicates a causal effect between heart irradiation and survival. It will be challenging to reduce the setup uncertainty even further; thus, increased focus on dose constraints on the heart seems warranted.

Online adaptive radiotherapy potentially reduces toxicity for high-risk prostate cancer treatment.

BACKGROUND AND PURPOSE: With daily, MR-guided online adapted radiotherapy (MRgART) it may be possible to reduce the PTV in pelvic RT. This study investigated the potential reduction in normal tissue complication probability (NTCP) of MRgART compared to standard radiotherapy for high-risk prostate cancer. MATERIALS AND METHODS: Twenty patients treated with 78 Gy to the prostate and 56 Gy to elective pelvic lymph nodes were included. VMAT plans were generated with standard clinical PTV margins. Additionally to the planning MR, patients had three MRI scans during treatment to simulate an MRgART. A reference plan with PTV margins determined for MRgART was created per patient and adapted to each of the following MRs. Adapted plans were warped to the planning MR for dose accumulation. The standard plan was rigidly registered to each adaptation MR before it was warped to the planning MR for dose accumulation. Dosimetric impact was compared by DVH analysis and potential clinical effects were assessed by NTCP modeling. RESULTS: MRgART yielded statistically significant lower doses for the bladder wall, rectum and peritoneal cavity, compared to the standard RT, which translated into reduced median risks of urine incontinence (ΔNTCP 2.8%), urine voiding pain (ΔNTCP 2.8%) and acute gastrointestinal toxicity (ΔNTCP 17.4%). Mean population accumulated doses were as good or better for all investigated OAR when planned for MRgART as standard RT. CONCLUSION: Online adapted radiotherapy may reduce the dose to organs at risk in high-risk prostate cancer patients, due to reduced PTV margins. This potentially translates to significant reductions in the risks of acute and late adverse effects.

First multicentre experience of SABR for lymph node and liver oligometastatic disease on the unity MR-Linac.

The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

Dose accumulation for MR-guided adaptive radiotherapy: From practical considerations to state-of-the-art clinical implementation.

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies-which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation-can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI pixel values do not contain the quantitative information used for dose calculation. In this review, we discuss considerations for dose accumulation specific to MRgART and in relation to current MR-linac clinical workflows. We present a general dose accumulation framework for MRgART and discuss relevant quality assurance criteria. Finally, we highlight the clinical importance of dose accumulation in the ART era as well as the possible ways in which dose accumulation can transform clinical practice and improve our ability to deliver personalized RT.