MR-guided Online Adaptive Radiotherapy Research Articles

Investigation of intrafractional spinal cord and spinal canal movement during stereotactic MR-guided online adaptive radiotherapy for kidney cancer.

This study aimed to investigate the intrafractional movement of the spinal cord and spinal canal during MR-guided online adaptive radiotherapy (MRgART) for kidney cancer. All patients who received stereotactic MRgART for kidney cancer between February 2022 and February 2024 were included in this study. Patients received 30-42 Gy in 3-fraction MRgART for kidney cancer using the Elekta Unity, which is equipped with a linear accelerator and a 1.5 Tesla MRI. MRI scans were performed at three points during each fraction: for online planning, position verification, and posttreatment assessment. The spinal cord was contoured from the upper edge of Th12 to the medullary cone, and the spinal canal was contoured from Th12 to L3, using the first MRI. These contours were adjusted to the second and third MR images via deformable image registration, and movements were measured. Margins were determined via the formula "1.3×Σ+0.5×σ" and 95% prediction intervals. A total of 22 patients (66 fractions) were analyzed. The median interval between the first and third MRI scans were 38 minutes. The mean ± standard deviation of the spinal cord movements after this interval were -0.01 ± 0.06 for the x-axis (right-left), 0.01 ± 0.14 for the y-axis (caudal-cranial), 0.07 ± 0.05 for the z-axis (posterior-anterior), and 0.15 ± 0.08 for the 3D distance, respectively. The correlation coefficients of the 3D distance between the spinal cord and the spinal canal was high (0.92). The calculated planning organ at risk volume margin for all directions was 0.11 cm for spinal cord. The 95% prediction intervals for the x-axis, y-axis, and z-axis were -0.11-0.09 cm, -0.23-0.25 cm and -0.14-0.03 cm, respectively. Margins are necessary in MRgART to compensate for intrafractional movement and ensure safe treatment delivery.

Deep learning-based automatic contour quality assurance for auto-segmented abdominal MR-Linac contours

Objective.Deep-learning auto-segmentation (DLAS) aims to streamline contouring in clinical settings. Nevertheless, achieving clinical acceptance of DLAS remains a hurdle in abdominal MRI, hindering the implementation of efficient clinical workflows for MR-guided online adaptive radiotherapy (MRgOART). Integrating automated contour quality assurance (ACQA) with automatic contour correction (ACC) techniques could optimize the performance of ACC by concentrating on inaccurate contours. Furthermore, ACQA can facilitate the contour selection process from various DLAS tools and/or deformable contour propagation from a prior treatment session. Here, we present the performance of novel DL-based 3D ACQA models for evaluating DLAS contours acquired during MRgOART.Approach.The ACQA model, based on a 3D convolutional neural network (CNN), was trained using pancreas and duodenum contours obtained from a research DLAS tool on abdominal MRIs acquired from a 1.5 T MR-Linac. The training dataset contained abdominal MR images, DL contours, and their corresponding quality ratings, from 103 datasets. The quality of DLAS contours was determined using an in-house contour classification tool, which categorizes contours as acceptable or edit-required based on the expected editing effort. The performance of the 3D ACQA model was evaluated using an independent dataset of 34 abdominal MRIs, utilizing confusion matrices for true and predicted classes.Main results.The ACQA predicted 'acceptable' and 'edit-required' contours at 72.2% (91/126) and 83.6% (726/868) accuracy for pancreas, and at 71.2% (79/111) and 89.6% (772/862) for duodenum contours, respectively. The model successfully identified false positive (extra) and false negative (missing) DLAS contours at 93.75% (15/16) and %99.7 (438/439) accuracy for pancreas, and at 95% (57/60) and 98.9% (91/99) for duodenum, respectively.Significance.We developed 3D-ACQA models capable of quickly evaluating the quality of DLAS pancreas and duodenum contours on abdominal MRI. These models can be integrated into clinical workflow, facilitating efficient and consistent contour evaluation process in MRgOART for abdominal malignancies.

Evaluation of Deep Learning Clinical Target Volumes Auto-Contouring for Magnetic Resonance Imaging-Guided Online Adaptive Treatment of Rectal Cancer

IntroductionSegmentation of clinical target volumes (CTV) on medical images can be time-consuming and is prone to inter-observer variation (IOV). This is a problem for online adaptive radiotherapy, where CTV segmentation must be performed every treatment fraction, leading to longer treatment times and logistic challenges. Deep learning (DL)-based auto-contouring has the potential to speed up CTV contouring. But its current clinical use is limited. One reason for this is that it can be time-consuming to verify the accuracy of CTV contours produced using auto-contouring, and there is a risk of bias being introduced. To be accepted by clinicians, auto-contouring must be trustworthy. Therefore, there is a need for a comprehensive commissioning framework when introducing DL-based auto-contouring in clinical practice. We present such a framework and apply it to an in-house developed DL model for auto-contouring of the CTV in rectal cancer patients treated with MR-guided online adaptive radiotherapy. Material and methodsThe proposed framework for evaluating DL-based auto-contouring consists of three steps: 1. Quantitative evaluation of the model's performance and comparison with IOV2. Expert observations and corrections3. Evaluation of the impact on expected volumetric target coverage.These steps are performed on independent datasets. The framework is applied to an in-house trained nnU-Net model, using the data of 44 rectal cancer patients treated at our institution. ResultsThe framework established that the model's performance after expert corrections was comparable to IOV, and while the model introduced a bias, this had no relevant impact on clinical practice. Additionally, we found a substantial time gain without reducing quality as determined by volumetric target coverage. DiscussionOur framework provides a comprehensive evaluation of the performance and clinical usability of target auto-contouring models. Based on the results, we conclude that the model is eligible for clinical use.

Inter-fractional Assessment during MR-guided Online Adaptive Radiotherapy for Glioblastoma

Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study aimed to assess the feasibility and potential benefits of MR-guided online adaptive radiotherapy (MRgOART) for patients with glioblastoma. Twenty consecutive patients with glioblastoma were treated with MRgOART of 60 Gy in 30 fractions by the 1.5 T MR-Linac. The MRgOART fractions employed daily MR scans and the contours were utilized to create each adapted plan. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on MRI of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3 ... Fx30) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume (∆V), Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. The reference treatment plans were generated using step-and-shoot IMRT and utilized 7-9 beam groups on original CT. Before the treatment, a synthetic CT (sCT) quality assurance (QA) process was performed to assess the dose accuracy of bulk relative electron density (rED) assignment for online MRI based treatment plan in terms of gamma analysis, point dose comparison and dose volume histogram (DVH) parameters. Then, the online adaptative treatment plans were obtained by re-optimizing based on the contours on daily pre-treatment MRI by "adapt to shape" workflow. Non-adaptive plans for each patient were generated by recalculating the dose from the reference plans on daily online MRI by "adapt to position" workflow. GTV and CTV coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. For both criteria, the 1%/1mm (98.58%±0.15%) and 2%/2mm (99.88%±0.18%) gamma passing rate results were always clinically acceptable in sCT QA process. The differences on point dose and DVH parameters between the plans based on sCT and original CT were less than 1%. A total of 20 patients with 600 fractions were evaluated. The results showed that large inter-fractional changes for GTV limited the efficacy of radiation therapy (DSC: 0.78±0.08, HD: 20.94±3.64mm, ∆V: 2.92%±6.36%). The inter-fractional CTV changes were smaller (DSC: 0.91±0.04, HD: 15.31±3.09mm, ∆V: 1.41%±1.29%). GTV coverage of non-adaptive plans was below the prescribed coverage in 228/600 fractions (38%), with 90 (15%) failing by more than 10%. For CTV coverage of non-adaptive plans, the changes were less than 5%. Online adaptative plans improved GTV and CTV coverage significantly (p<0.001) to 99%. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p<0.001). Significant inter-fractional tumor changes could be found during radiotherapy in patients with glioblastoma treated by the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions.

Biologically Equivalent Dose Comparison Between Magnetic Resonance-Guided Adaptive and Computed Tomography-Guided Internal Target Volume-Based Stereotactic Body Radiotherapy for Liver Tumors.

Background and aim Magnetic resonance (MR) imaging has been increasingly adopted in the field of radiotherapy, and the most advanced MR image-guided radiotherapy is known as MR-guided online adaptive radiotherapy (MRgOART), which integrates MRI and linac systems. Few attempts have yet been made to directly compare treatment outcomes between the MRgOART and standard computed tomography (CT)-guided radiotherapy (CTgRT). Besides, it is reported that the biologically equivalent dose (BED) may be a good predictor of the local control (LC) and the overall survival (OS) for liver tumors. The purpose of this study is to compare the BEDs between the MRgOART and the CTgRT by way of virtual isotoxic planning for liver tumors. The hypothesis of this study is therefore that the MRgOART increases LC and OS as compared to the CTgRT. Materials and methods Using the five patient cases available, isotoxic planning was performed. For CTgRT, an internal target volume (ITV) was defined, and the planning target volume (PTV) was created by adding an isotropic margin of 10 mm. For MRgRT, a gross tumor volume (GTV) was defined, and the PTV was created by adding an isotropic margin of 5 mm. Each tumor size was virtually adjusted so that the CTgRT plans resulted in BED <100 Gy under the condition that the nearest organs at risk receive maximum tolerated doses. Subsequently, the BED was recalculated for MRgOART plans with the adjusted tumor size. Results and discussion It was found that the BEDs of the MRgOART plans always exceeded 100 Gy and were approximately 20 Gy larger than those of the corresponding CTgRT plans. Literature shows that superior overall survival rates for liver tumors were observed when BED was >100 Gy as compared to BED <100 Gy, suggesting that MR-guided adaptive planning may potentially lead to better treatment outcomes for liver tumors. We have also observed a case where the duodenum largely moved and abutted the liver after the CT images were acquired, indicating a significant disadvantage of the standard CTgRT because such abutting is not observable by the cone-beam CT immediately before treatment. Conclusion A highly accelerated evidence-creation procedure to suggest the clinical superiority of MRgOART has been arguably proposed with promising results. The sample size is small and limits the extent to which the findings in this study can be generalized. Further virtual clinical trials within the radiotherapy community are awaited with more clinical outcomes data.

Longitudinal Assessment of Gross Tumor Volume in Abdominal and Pelvic Patients Undergoing MR-Guided Online Adaptive Radiotherapy as a Predictive Biomarker of Treatment Response

<h3>Purpose/Objective(s)</h3> MR-guided radiotherapy (MRgRT) provides longitudinal MR images during RT, and enables the evaluation of potential imaging biomarkers of treatment response (TR). We investigated whether interfraction tumor volumetric changes correlated with ultimate radiographic response. <h3>Materials/Methods</h3> 131 patients underwent daily adaptive MRgRT of the pancreas (n=71), adrenal (n=27), abdominal lymph node (LN) (n=19), and pelvic LN (n=14) to a median of 50 Gy/5 fractions (fxs). For each adaptive fx, the simulation GTV was compared to the daily GTV on the 0.35 T TRUFI MR. GTV change (ΔGTV) was quantified as the % difference in GTV of the adapted fx compared to simulation. To ensure robustness, a minimum ΔGTV > ±1 cc was required for TR-correlation on post-RT diagnostic MR. Patients were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using RECIST criteria, and TR was correlated to fx with the largest ΔGTV. <h3>Results</h3> Median follow up was 22.5 months. Numerically (not statistically significant) the largest interfraction ΔGTV for the entire cohort was observed at fx 3 (14.2%) compared to 6.8, 10.2, 8.9, and 13.1% for fxs 1, 2, 4, and 5, respectively. For pancreas, adrenal, abdominal LN, and pelvic LN, the median ΔGTV at fx 3 (ΔGTV_fx3) was -5.1, 20.8, 27.5, and 3.4%, respectively; meaning GTV increased, on average, for all sites except pancreas. ΔGTV_fx3 as a function of TR is displayed in the Table. ΔGTV_fx3 for pancreas and pelvic LN was <10%. For adrenals achieving post-RT CR, PR, SD, larger ΔGTV_fx3 were observed, with median of 23.8, 20.8, and 26.3%, respectively, with extreme case of 41% increase in a patient achieving a subsequent CR. For PD adrenal lesions, the ΔGTV_fx3 is 0. These findings putatively suggest an acute SBRT-related inflammatory response resulting in subsequent disease stability or regression. In contrast, for abdominal LN, no such significant ΔGTV_fx3 is noted for CR, PR, or SD, but for PD, the ΔGTV_fx3 increases substantially to 39.1%_. <h3>Conclusion</h3> Daily adaptive MRgRT enabled interfraction tracking of ΔGTV that was retrospectively correlated to TR. Numerically, we observed the greatest ΔGTV at fx 3. However, this change was seen primarily in adrenal and abdominal nodal lesions, and not other sites. The significance of this change is non-uniform, in that for adrenal lesions, responders were more likely to have volumetric increase, whereas for abdominal LN, progressors were more likely to have volumetric increase. These preliminary findings are being rigorously tested through a retrospective, multi-observer blinded contouring exercise, and also being extended to other disease sites, prior to formulating a clinically actionable hypothesis.

Development and implementation of an automatic air delineation technique for MRI-guided adaptive radiation therapy

Objective. Auto-delineation of air regions on daily MRI for MR-guided online adaptive radiotherapy (MRgOART) of abdominal tumors is challenging since the air packets occur randomly and their MR intensities can be similar to some other tissue types. This work reports a new method to auto-delineate air regions on MRI. Approach. The proposed method (named DIFF method) consists of (1) generating a combined volume V comb , which is a union of the air-containing organs on a reference MR image offline, (2) transferring V comb from the reference MR to a daily MR via DIR, (3) combining the transferred V comb with a region of high DIR inaccuracy, and (4) applying a threshold to the obtained final combined volume to generate the air volumes. The high DIR inaccuracy region was calculated from the absolute difference between the deformed daily and the reference images. This method was tested on 36 abdominal daily MRI sets acquired from 7 patients on a 1.5 T MR-Linac. The performance of DIFF was compared with alternative auto-air generation methods that (1) does not account for DIR inaccuracies, and (2) uses rigid registration instead of DIR. Main results. The results show that the proposed DIFF method can be fully automated and can be executed within 25 s. The Dice similarity coefficient of manual and DIFF auto-generated air contours was >92% for all cases, while it was 90% for the alternative auto-delineation methods. Dosimetrically, the auto-generated air regions using DIFF resulted in practically identical DVHs as those generated by using manual air contours. Significance. The DIFF method is robust and accurate and can be implemented to automatically consider the inter- and intra- fractional air volume variations during MRgOART for abdominal tumors. The use of DIFF method improves dosimetric accuracy as compared to other methods, especially beneficial for the patients with large daily abdominal air volume variations.

PD-0502 Stereotactic MR guided online adaptive radiotherapy for abdominal and pelvic lymph node metastases

PD-0502 Stereotactic MR guided online adaptive radiotherapy for abdominal and pelvic lymph node metastases

OC-0775 Dosimetric consistency between MR-only and deformed CT for MR-guided online adaptive radiotherapy

OC-0775 Dosimetric consistency between MR-only and deformed CT for MR-guided online adaptive radiotherapy

Dosimetric benefit of MR-guided online adaptive radiotherapy in different tumor entities: liver, lung, abdominal lymph nodes, pancreas and prostate

BackgroundHybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.MethodsFifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.ResultsAll subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.ConclusionWith online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.

Novel modified patient immobilisation device with an integrated coil support system for MR-guided online adaptive radiotherapy in the management of brain and head-and-neck tumours.

Magnetic resonance imaging (MR)-guided online adaptive radiotherapy is a promising technique in the field of radiation oncology providing excellent visualisation of soft-tissues, and allowing for online plan adaptation and tumour tracking. In order to facilitate the accurate dose delivery to the target volume while sparing healthy surrounding normal tissue in the brain or head-and-neck (H&N) region, precise patient immobilisation with good image quality is pertinent. Herein, we present a customised thermoplastic mask holder with an integrated anterior MR receiver coil support system for MR-guided online adaptive radiotherapy in the brain and head-and-neck region. The approved medical product was developed by Innovative Technologie Voelp (IT-V), Innsbruck, Austria. MR image uniformity measurements demonstrated improved image uniformity at the expense of decreased signal-to-noise ratio due to a more defined and larger distance between the anterior receiver coil and the phantom or patient. This integrated coil support system represents a practical solution facilitating stable and reproducible anterior coil placement while maintaining the thermoplastic mask holder functionality, a widely established immobilisation technique.

Modelling of Dosimetric Impact of Visceral Organ Variability During MRI-Guided Hypofractionated Stereotactic Ablative Radiotherapy (SABR) to the Pancreas

Evaluation of visceral organ motion and dosimetric impact during pancreas SABR in non-patient subjects during the time frame of an MR-guided online adaptive radiotherapy (MRgART).Breath-hold MR images were acquired from six subjects on 0.35T MR-Linac at 30-minute intervals up to 90 minutes (intra-fraction images: F1a-d). A fifth image was acquired on a separate day (inter-fraction images: F2). SABR plans were generated to a prescription of 50 Gy in 5 fractions to mock pancreatic head tumors (median GTV 9 cc (range 8-10)) based on F1a images. Dose to visceral organs were recalculated on F1b-d and F2 images. For each visceral organ, the dose constraints used were V36 < 0.1 cc (volume of organ receiving 36 Gy < 0.1 cc), V33 < 0.5 cc and V25 < 10 cc. Volume of stomach, duodenum, small bowel and large bowel within 3 cm and 0.5 cm of PTV were recorded from each image and compared. Dosimetric impact of visceral organ motion was evaluated by comparing dose delivered to visceral organs at baseline (F1a) and the other time points (F1b-d, F2).For each subject, there was low degree of correlation between timepoint and volume of visceral organ within 3cm and .5cm of PTV (R = 0.01 and .23). Dose constraint violations were observed intra-fractionally. The highest number of dose constraint violations occurred for the duodenum, followed by stomach and large bowel (see table). No dose constraint violation was observed for the small bowel. The median magnitude of dose violations, defined as volume of organ receiving dose above constraints over mandatory volume limit, were statistically significantly lower in intra-fraction compared to inter-fraction images for the duodenum (median = .6 vs 1.9, P = 0.01).There is irregular visceral organ motion within the time frame of pancreas MRgART. This would not have been accounted for with respiratory gating. Although the magnitude of intra-fraction dose violation appears to be lower compared to inter-fraction, violations may have significant impact on toxicity. These violations are likely to be present in patients currently undergoing MRgART. However, given the reported low toxicity of dose-escalated MRgART, estimation of normal tissue toxicity based on current constraints may be limited. Further work is required to validate these findings in patients. Management of peristalsis may need to be considered. Table: Total number of dose constraint violations at each time point for 6 subjects. Each visceral organ has to meet 3 constraints V36, V33 and V25.

Assessment of Dose Accuracy for MR-Guided Online Adaptive Radiotherapy for Nasopharyngeal Carcinoma

MR-guided radiotherapy relies on the daily assignment of a relative electron density (rED) map to acquire the fraction specific dose calculation. The approach to acquire the rED map is used bulk rED assignment based on the rED values of the delineated region of interests (ROIs) to generate a synthetic CT (sCT). This study aims to evaluate the dose accuracy of this approach for application in 1.5 T MR-Linac, to assess the reliability of this approach in the case of online adaptive MR-guided radiotherapy for Nasopharyngeal Carcinoma (NPC) patients.The original CT and MRI T2 were acquired for 10 NPC patients and targets, organs at risk (OARs), bone and air regions were delineated on original CT in a treatment planning software. Each patient's MRI/CT image pair was aligned using a rigid registration algorithm, and the contours were copied to MRI from original CT. The sCT was then generated in MRI using bulk rED assignment approach, based on the rED values of the delineated region of interests (ROIs). Three different types of sCT images were generated: The sCTICRU uses the rED values recommended by ICRU46, the sCTtailor uses the patient-specific mean rED values, and the sCTHomogeneity was created using water equivalent value of 1 g/cm3 for entire patient data set. The same treatment plan was calculated on three sCTs and original CT. The dose calculation accuracy was investigated in terms of gamma analysis, point dose comparison and dose volume histogram (DVH) parameters.For both criteria, 1%/1mm and 2%/2mm gamma passing rate results of plans on sCTtailor were always higher than plans on sCTICRU and sCTHomogeneity when compared with original CT based plans (P = 0.005). The difference on point dose in high dose planning target volume for each case calculated on sCTtailor (-0.14% ± 1.44%) was smaller if compared to those calculated on sCTICRU (-8.77% ± 2.33%) and sCTHomogeneity (1.65% ± 2.57%). The DVH differences for plan based on sCTtailor were much smaller than sCTICRU and sCTHomogeneity.The sCT generated with bulk rED assignment approach guarantees an acceptable level of dose accuracy for NPC patients with 1.5 T MR-Linac, making this approach suitable to online adaptive MR-guided radiotherapy. The accuracy can be improved by using patient-specific rED values.

Establishing the Gastroduodenal Maximum Tolerated Dose for Ablative 5-Fraction Stereotactic MR-guided Online Adaptive Radiation Therapy (SMART) in a Novel Swine Model

Daily variations in abdominal anatomy introduce significant uncertainty in estimating the maximum tolerated dose (MTD). We investigated the gastroduodenal toxicity using stereotactic MR-guided online adaptive radiotherapy (SMART) to precisely control the dose to a novel swine model that closely matches human physiology and can be maintained at 80 kg. We hypothesized for a cumulative SMART course of 50 Gy in 5 fractions to the pancreas, the duodenum MTD is significantly > 37 Gy to 0.5 cc (D0.5cc).A total of 18 WMSTM were included at 3 duodenal dose levels: 37 Gy (n = 12), 43.5 Gy (n = 3), and 50 Gy (n = 3) in 5 fractions. We defined MTD as: > 10% (≥2 of 12) WMSTM present with dose limiting toxicity (DLT). A DLT was defined as ≥ Grade 3 non-hematologic toxicity due to RT per NCI CTCAE v4.0. All WMSTM underwent SMART on a clinical MR-guided radiotherapy (MRgRT) LINAC, under ventilation at breath hold (BH). Plans were IMRT and prescribed 50 Gy/5 fractions to pancreatic head, while maintaining uniform dose level (37, 43.5, 50 Gy) to duodenal circumference at 3 cm inferior to pylorus sphincter, typical uniform irradiated range 3-9 cc based on duodenal diameter. Circumference approach was used to eliminate underestimation of cumulative D0.5cc. Duodenal hotspot was 1.03% of the dose level (37, 43.5, 50 Gy) to 2 cc, 1.05% to 0.1 cc. Gated BH delivery was performed with sagittal plane tracking of the duodenum at 4 frames per second. Toxicity monitoring occurred for 30 days post-RT. Fecal occult blood test (FOBT) was done during RT and toxicity monitoring. Endoscopy occurred 14 days post-RT. Gross pathology was obtained at time of necropsy, 30 days post-RT.For the 37 Gy level, 1 of 12 WMSTM presented with DLT-pinpoint ulcer with surface damage on gross pathology (30 days post-RT). No DLT for 2 of 3 WMSTM at the 43.5 Gy level. One WMSTM at the 43.5 Gy level perforated on endoscopy, potentially due duodenal wall degradation and unknown RT-induced DLT on gross exam of emergency necropsy. Endoscopy was eliminated for the 50 Gy level. DLT was found for 2 of 3 WMSTM at the 50 Gy level upon gross pathology at necropsy, with each subject having 2-3 visible ulcerations at level of RT. One WMSTM at the 50 Gy level had duodenal pre-ulcer erosion at necropsy. All three WMSTM at 50 Gy level had visibly damaged papilla at necropsy. Another WMSTM at the 50 Gy level had common bile duct blockage, gall bladder obstruction, and jaundice at necropsy. FOBT were negative for all 18 WMSTM at 14 days post-RT.A duodenum D0.5cc of 37 Gy in 5 fractions was found to be safe in a swine model for a 50 Gy SMART course to the pancreas, showing the duodenal MTD is > 37 Gy - an increase from the RTOG 1112 limit (i.e., 30 Gy). Our results translate to a recommended MTD in human subjects and can potentially allow for greater tumor dose escalation and survival outcomes in future pancreatic patients. We are currently pursuing an expansion cohort to evaluate the MTD at 43.5 Gy.

Inter- and Intrafraction Bladder and Rectum Motion in Patients With Cervical Cancer Under MR-Guided Radiotherapy on a 1.5T MR-Linac

Internal bladder and rectum motion occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes. The MR-Linac system allows for daily MR image guidance and real-time imaging throughout the treatment fraction, which is ideal for managing and monitoring both inter-fraction and intrafraction motion, without incurring additional radiation exposure. The study is to evaluate bladder and rectum inter- and intrafraction motion using MRI during the full course of MR-Linac radiotherapy fractions, in preparation of MR-guided online adaptive radiotherapy.Five stage ⅡA - ⅢB cervix cancer patients were treated with 25 × 1.8 Gy fractions on a 1.5T MR-Linac. Each fraction, pre-treatment MRI scans were obtained at the start of every treatment session, and post-treatment MRI scans were obtained at the end of every treatment session. The bladder and rectum were delineated on each MRI by the same radiation oncologist. Inter-fraction and intrafraction variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD), mean distance to agreement (MDA), volume (V) and dose volume parameters.Large inter-fraction motion was found for bladder and rectum due to their filling variation (Bladder: DSC: 0.68 ± 0.17, HD: 30.58 ± 15.32, MDA: 7.77 ± 4.65, V: -23.02% ± 13.13%, Dmean: 2.23% ± 7.10; Rectum: DSC: 0.69 ± 0.04, HD: 22.98 ± 4.02, MDA: 3.45 ± 0.63, V: 13.57% ± 18.09%, Dmean: 0.4% ± 0.7%). Median in-room treatment time pre fraction was 35 min which was much longer than conventional treatment time. The intrafraction motion for bladder was obvious that was explained by the bladder filling variation due to prolonged in-room treatment time per fraction (DSC: 0.88 ± 0.07, HD: 14.66 ± 8.48, MDA: 1.89 ± 1.15, V: 13.06% ± 15.66%, Dmean: -0.89% ± 2.45%). The intrafraction rectum motion was much smaller.Considerable inter-fraction bladder and rectum motion is observed and intrafraction bladder motion which caused by longer treatment time is also obvious in cervical cancer patients on 1.5T MR-Linac. Intrafraction MR-guided online adaptive radiotherapy may potentially further correct this motion.S. Ding: None. H. Liu: None. B. Wang: None. Y. Li: None. B. Liu: None. Y. Ouyang: None. X. Huang: None.

OC-0469: MR-guided online adaptive radiotherapy for muscle invasive bladder cancer: First UK experience

OC-0469: MR-guided online adaptive radiotherapy for muscle invasive bladder cancer: First UK experience

A Novel Pre-plan Technique for On-table Adaptation of Pancreatic Stereotactic MR-guided Online Adaptive Radiotherapy

Currently on-table adaptive radiotherapy (ART) is performed by daily re-optimization of initial planning objectives developed from the initial simulation anatomy. Eliminating the initial plan creation may reduce start time, simulation and planning resources, and improve clinical efficacy. We hypothesize that for the treatment of pancreas SBRT using ART, adapting a generic pre-plan to the anatomy of the day results in dosimetrically equivalent plan quality of adapting a patient-specific initial plan to the anatomy of the day. Thirty-eight (n = 38) patients were treated for pancreatic cancer with MR-guided online adaptive radiotherapy (MRgoART) to 50 Gy/5 fractions (fx). An initial plan was developed over 8 days. For on-table adaptation, the initial plan was adapted to the anatomy of the day for each fx and delivered. Retrospectively, we developed a single template pre-plan technique based on optimization objectives from simulation anatomy across 38 patients. To assess feasibility of the pre-plan technique, we adapted the template pre-plan to the on-table fx 3 anatomy of the day (ADAPTtemplate-to-fx3) and compared the plan quality to the patient-specific initial plan adapted to fx 3 anatomy of the day (ADAPTsim-to-fx3) for all patients. Adapted plans were single-optimized and then normalized to greatest violated OAR. RTOG plan quality metrics were evaluated for target coverage (TC) (PTV V100%/PTV vol), homogeneity index (HI) (PTV D2%/ D98%), high dose conformity (PITV), low dose conformity (D2cm), and gradient (R50%). PTV coverage of V100%, D80% were evaluated. Seventy-six (n = 76) adaptions were performed for ADAPTtemplate-to-fx3 and ADAPTsim-to-fx3. Due to plan-normalization, no OARs were violated. PTV coverage was improved for respective ADAPTtemplate-to-fx3 compared to ADAPTsim-to-fx3 for 58% of cases for D80% (45.8±5.9 vs 45.3±9.1, p = 0.8), 61% of cases for TC (0.66±0.30 vs 0.55±0.30, p = 0.1), and 66% of cases for V100% (63±27% vs 55±32% p = 0.2). Homogeneity and conformity indices between respective ADAPTtemplate-to-fx3 and ADAPTsim-to-fx3 were 0.72±0.39 vs 0.60±0.41, p = 0.2 (PITV), 1.94±0.71 vs 1.52±0.22, p<0.001 (HI), 3.14±1.45 vs 3.52±1.80, p = 0.3 (R50%), and 0.61±0.12 vs 0.58±0.22, p = 0.5 (D2cm). For online adaptation in pancreas SBRT, 66% of the single-optimized template plan had improved coverage (PTV V100) with no OAR violation compared to the patient-specific single-optimized initial plan to the anatomy of the day. Given that the plan quality was not significantly different, this works supports AI-plan automation for patients receiving online ART, potentially eliminating the need for initial plan creation and even simulation. Future investigation of the feasibility and efficacy will be launched in a Phase I/II randomized clinical trial between template plan and initial plan for MRgoART.

Impact of Healthy Volunteer MR-Linac Imaging on Clinical Implementation of Stereotactic MR-Guided Online Adaptive Radiotherapy

Stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) combines real-time MR imaging with RT delivery, allowing for online adaptive planning and continuous motion management. However, uncertainty remains in optimal patient positioning, image quality standards, and contouring guidelines for SMART. To determine the optimal combination of MR sequence parameters, coil and patient positioning, and treatment immobilization, we conducted a healthy volunteer (HV) study utilizing a 0.35T MR-Linac (MRL). We hypothesized that with optimization of these parameters, image quality and SMART workflows for HVs would be acceptable across a range of clinically relevant organs, facilitating subsequent patient imaging. The HV study was approved by the IRB. Adults of all races and genders were included. MR simulation and simulated SMART were performed in HVs on an MRL. For each scan, the following parameters were assessed on a scale from 1-5 (5 = extremely high, 1 = extremely poor): visibility of target, visibility of nearby normal organs, and overall image quality. Adaptive recontouring time was recorded. With IRB approval, we retrospectively reviewed recontouring times for the first fraction for the first 18 patients treated clinically with SMART. HV and clinical times were compared with a t-test (alpha = 0.05). 46 HVs consented to the study. 18 underwent simulated treatments that included simulation of all aspects of SMART clinical workflow, except RT delivery, and targeted the following organs: adrenal, prostate, pancreas, lung, kidney, and brain. Average visibility of target and nearby organs were 4.58 and 4.62, respectively, and average overall image quality was 4.62 with a range of 4-5 for all measures. The average recontouring time was 15 minutes (range 4-35) in the HVs, comparable to an average of 16.1 minutes (range 7-33) in patients (p = 0.886). The clinical cases targeted adrenal, prostate, pancreas, lung, and pelvic and abdominal nodes. HV scanning on an MRL resulted in acceptable image quality and target visibility for a range of organs. Contouring time, the longest step in our workflow, was well-simulated in HVs, with similar times achieved clinically. The organs targeted in HVs correlated well with the organs treated clinically. The HV study provided a non-clinical environment to optimize all aspects of SMART, except for RT delivery. Further study is needed to determine the optimal number of HV scans required to prepare for clinical implementation of SMART.

Assessment of Intrafraction Cervico-Uterine Motion in the Definitive Treatment of Locally Advanced Cervical Cancer Using MR-Guided Radiotherapy

To account for intrafraction motion, patients receiving intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer have an internal target volume (ITV) defined from bladder-full and bladder-empty CT simulation scans. We hypothesized that through daily volumetric magnetic resonance (MR) imaging for setup and treatment, we can assess cervico-uterine motion and create an intrafraction-ITV independent of interfraction bladder changes, and therefore dispense with the full-bladder to empty-bladder ITV paradigm. In this IRB-approved, study patients with locally advanced cervical cancer received IMRT with brachytherapy. IMRT was delivered on a clinical MR-guided radiotherapy (MRgRT) Linac. All patients received a pre-treatment (pre-tx) and post-treatment (post-tx) 0.35T balanced steady-state free precession MR scans in treatment position. The intrafraction cervico-uterine motion was assessed through segmentation of the clinical target volume (CTV) by a gynecological radiation oncologist on each scan. The pre-tx and post-tx MR scans were in the same frame of reference, and any residual patient motion was removed through a rigid registration of the post-tx MR scan to the pre-tx MR scan based on bony anatomy. All post-tx contours were rigidly copied to the pre-tx MR scans. The maximum and mean difference in spatial position between the pre-tx and post-tx MR scans were quantified using maximum Hausdorff distance (HD) and mean distance to agreement (MDA), respectively. Mean, standard deviation, and 95% confidence interval were calculated to determine the intrafraction MR-based internal target volume (ITVMRgRT). In total, 19 same day sessions (N = 38 scans) of intrafraction motion were assessed. Minimal patient voluntary motion was observed across rigid registrations with respect to bony anatomy. The average time between the pre-tx and post-tx MR scans was 14.3 ± 7.1 minutes (mean ± standard deviation), resembling a hypothetical time of on-table adaptation and treatment. The average maximum HD was 0.88 ± 0.46 cm (95% CI 0.668 - 1.08) and average MDA was 0.08 ± 0.07 cm (95% CI 0.05- 0.118). Due to HD’s sensitivity to outliers, a more robust metric (i.e., MDA) was utilized for margin calculation. The ITVMRgRT margin necessary to encompass the MDA for 95% of the intrafraction motion was 0.12 cm; therefore, we propose an ITVMRgRT of 0.15 cm given the non-partial voxelization of segmentation. This work supports margin reduction of the ITV to ITVMRgRT of 0.15 cm when using daily MR-guided online adaptive radiotherapy. Given the maximum setup uncertainty is limited in MRgRT to spatial resolution of the real-time cine imaging sequence, we propose an ITVMRgRT-PTV margin of 0.3 cm. Therefore, our total CTV to PTV margin is 0.45 cm.

4D-MRI driven MR-guided online adaptive radiotherapy for abdominal stereotactic body radiation therapy on a high field MR-Linac: Implementation and initial clinical experience

Background and purposeIn this report, we describe our implementation and initial clinical experience using 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) for abdominal stereotactic body radiotherapy (SBRT) on the Elekta Unity MR-Linac. Materials and methodsEleven patients with abdominal malignancies were treated with free-breathing SBRT in three to five fractions on a 1.5 T MR-Linac. Online adaptive plans were generated using Adapt-To-Position (ATP) or Adapt-To-Shape (ATS) workflows based on motion averaged or mid-position images derived from a pre-beam 4D-MRI. A high performance server positioned on the local MR-Linac machine network was utilized for 4D-MR image reconstruction. A parallel contour editing approach was employed in the ATS workflow. Intravoxel incoherent motion (IVIM) and T2 mapping sequences were acquired during adaptive planning in both ATP and ATS workflows for treatment response monitoring. Adaptive plans were delivered under real-time cine image motion monitoring. ResultsThe shortest 4D-MRI time-to-image was the motion averaged image, followed by mid position and respiratory binned images. In this cohert of patients, 50% of treatments utilized the ATS workflow; the remaining treatments utilized the ATP workflow. Mid-position images were utilized as daily planning images for two of the eleven patients. The mean daily adaptive plan secondary dose calculation and ArcCheck 3D Gamma passing rates were 97.5% (92.1–100.0%) and 99.3% (96.2–100.0%), respectively. The median overall treatment times for abdominal SBRT was 46 and 62 min for ATP and ATS workflows, respectively. ConclusionWe have successfully implemented and utilized a 4D-MRI driven MRgOART process with ATP and ATS workflows for free-breathing abdominal SBRT on a 1.5 T Elekta Unity MR-Linac.