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This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Magnetic resonance (MR)-guided radiation therapy (MRgRT) is a new technique for treatment of localized prostate cancer (PCa). We report the 12-month outcomes for the first PCa patients treated within an international consortium (the MOMENTUM study) on a 1.5T MR-Linac system with ultrahypofractionated radiation therapy., Methods and Materials: Patients treated with 5 × 7.25 Gy were identified. Prostate specific antigen-level, physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), and patient-reported outcomes (Quality of Life Questionnaire PR25 and Quality of Life Questionnaire C30 questionnaires) were recorded at baseline and at 3, 6, and 12 months of follow-up (FU). Pairwise comparative statistics were conducted to compare outcomes between baseline and FU., Results: The study included 425 patients with localized PCa (11.4% low, 82.0% intermediate, and 6.6% high-risk), and 365, 313, and 186 patients reached 3-, 6-, and 12-months FU, respectively. Median prostate specific antigen level declined significantly to 1.2 ng/mL and 0.1 ng/mL at 12 months FU for the nonandrogen deprivation therapy (ADT) and ADT group, respectively. The peak of genitourinary and gastrointestinal CTCAE toxicity was reported at 3 months FU, with 18.7% and 1.7% grade ≥2, respectively. The QLQ-PR25 questionnaire outcomes showed significant deterioration in urinary domain score at all FU moments, from 8.3 (interquartile range [IQR], 4.1-16.6) at baseline to 12.4 (IQR, 8.3-24.8; P = .005) at 3 months, 12.4 (IQR, 8.3-20.8; P = .018;) at 6 months, and 12.4 (IQR, 8.3-20.8; P = .001) at 12 months. For the non-ADT group, physician- and patient-reported erectile function worsened significantly between baseline and 12 months FU., Conclusions: Ultrahypofractionated MR-guided radiation therapy for localized PCa using a 1.5T MR-Linac is effective and safe. The peak of CTCAE genitourinary and gastrointestinal toxicity was reported at 3 months FU. Furthermore, for patients without ADT, a significant increase in CTCAE erectile dysfunction was reported at 12 months FU. These data are useful for educating patients on expected outcomes and informing study design of future comparative-effectiveness studies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Neurovascular bundle (NVB) and internal pudendal artery (IPA) sparing during magnetic resonance-guided radiotherapy (MRgRT) for prostate cancer aims for preservation of erectile function. Our present workflow involves daily online contouring and re-planning on a 1.5 T MR-linac, as alternative to conventional (rigid) translation-only corrections of the prostate. We compared planned dose for the NVB and IPA between strategies. Total planned dose was significantly lower with daily online contouring and re-planning for the NVB, but not for the IPA. For the NVB and IPA, the intrapatient difference between highest and lowest fraction dose was significantly smaller for the contouring and re-planning plans., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HV receives research funding from Elekta. The remaining authors declare no potential competing interests., (© 2022 The Author(s).)

Background and Purpose: Erectile dysfunction is a common adverse effect of external beam radiation therapy for localized prostate cancer (PCa), likely as a result of damage to neural and vascular tissue. Magnetic resonance-guided online adaptive radiotherapy (MRgRT) enables high-resolution MR imaging and paves the way for neurovascular-sparing approaches, potentially lowering erectile dysfunction after radiotherapy for PCa. The aim of this study was to assess the planning feasibility of neurovascular-sparing MRgRT for localized PCa., Materials and Methods: Twenty consecutive localized PCa patients, treated with standard 5×7.25 Gy MRgRT, were included. For these patients, neurovascular-sparing 5×7.25 Gy MRgRT plans were generated . Dose constraints for the neurovascular bundle (NVB), the internal pudendal artery (IPA), the corpus cavernosum (CC), and the penile bulb (PB) were established. Doses to regions of interest were compared between the neurovascular-sparing plans and the standard clinical pre-treatment plans., Results: Neurovascular-sparing constraints for the CC, and PB were met in all 20 patients. For the IPA, constraints were met in 19 (95%) patients bilaterally and 1 (5%) patient unilaterally. Constraints for the NVB were met in 8 (40%) patients bilaterally, in 8 (40%) patients unilaterally, and were not met in 4 (20%) patients. NVB constraints were not met when gross tumor volume (GTV) was located dorsolaterally in the prostate. Dose to the NVB, IPA, and CC was significantly lower in the neurovascular-sparing plans., Conclusions: Neurovascular-sparing MRgRT for localized PCa is feasible in the planning setting. The extent of NVB sparing largely depends on the patient's GTV location in relation to the NVB., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HV receives research funding from Elekta. The remaining authors declare no potential competing interests., (© 2021 The Author(s).)

Background and Purpose: In daily adaptive magnetic resonance (MR)-guided radiotherapy, plans are adapted based on the patient's daily anatomy. During this adaptation phase, prostate intrafraction motion (IM) can occur. The aim of this study was to investigate the efficacy of always applying a subsequent virtual couch shift (VCS) to counter IM that occurred during the daily contour and plan adaption (CPa) procedure., Material and Methods: One hundred fifty patients with low and intermediate risk prostate cancer were treated with 5x7.25 Gy fractions on a 1.5 T MR-Linac. In each fraction, contour adaptation and dose re-optimization was performed using the session's first MR-scan. IM that occurred here was countered using two methods. One patient group had selective VCS (sVCS) applied if the CTV reached outside the PTV on a second MR acquired during plan optimization. The other group had always VCS (aVCS) applied for any prostate shift greater than 1 mm. Remaining IM during beam delivery was determined using 3D cine-MR., Results: Percentage of fractions where a VCS was applied was 28% (sVCS) vs 78% (aVCS). Always applying VCS significantly reduced influences of systematic prostate IM. Population random and systematic median values in all translations directions were lower for the aVCS than sVCS group, but not for the population random cranial-caudal direction., Conclusion: Applying VCS after daily CPa reduced impact of systematic prostate drift in especially the posterior and caudal translation direction. However, due to the continuous and stochastical nature of prostate IM, margin reduction below 4 mm requires fast intrafraction plan adaption methods., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background and Purpose: Daily online adaptation of the clinical target volume (CTV) using MR-guided radiotherapy enables margin reduction of the planning target volume (PTV). This study describes the implementation and initial experience of MR-guided radiotherapy on the 1.5T MR-linac and evaluates treatment time, patient compliance, and target coverage, including an initial assessment of margin reduction., Materials and Methods: Patients were treated on a 1.5T MR-linac (7MV, FFF). At each fraction a 3D T2 weighted (T2w) MR-sequence was acquired on which the CTV was adapted after a deformable registration of the contours from the pre-planning CT scan. Based on the new contours a full online replanning was done after which a new 3D T2w MR-sequence was acquired for position verification. A 5 field Intensity Modulated Radiotherapy (IMRT) plan was delivered., Results: Forty-three patients with rectal cancer were treated with 25 Gy in 5 fractions of which 18 with reduced margins. In total, 204 of 215 fractions were delivered on the MR-linac all of which obtained a clinically acceptable treatment plan. Median in-room time per fraction was 48 min (interquartile range 8). No fractions were canceled or interrupted because of patient intolerance. CTV coverage after margin reduction was good on all post-treatment scans but one due to passing gas., Conclusion: MR-guided radiotherapy using daily full online recontouring and replanning on a 1.5T MR-linac for rectal cancer is feasible and currently takes about 48 min per fraction., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT., Material and Methods: Five low and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom., Results: Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions., Conclusion: This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Monitoring the intrafraction motion and its impact on the planned dose distribution is of crucial importance in radiotherapy. In this work we quantify the delivered dose for the first prostate patients treated on a combined 1.5T Magnetic Resonance Imaging (MRI) and linear accelerator system in our clinic based on online 3D cine-MR and treatment log files., Materials and Methods: A prostate intrafraction motion trace was obtained with a soft-tissue based rigid registration method with six degrees of freedom from 3D cine-MR dynamics with a temporal resolution of 8.5-16.9 s. For each fraction, all dynamics were also registered to the daily MR image used during the online treatment planning, enabling the mapping to this reference point. Moreover, each fraction's treatment log file was used to extract the timestamped machine parameters during delivery and assign it to the appropriate dynamic volume. These partial plans to dynamic volume combinations were calculated and summed to yield the delivered fraction dose. The planned and delivered dose distributions were compared among all patients for a total of 100 fractions., Results: The clinical target volume underwent on average a decrease of 2.2% ± 2.9% in terms of D99% coverage while bladder V62Gy was increased by 1.6% ± 2.3% and rectum V62Gy decreased by 0.2% ± 2.2%., Conclusions: The first MR-linac dose reconstruction results based on prostate tracking from intrafraction 3D cine-MR and treatment log files are presented. Such a pipeline is essential for online adaptation especially as we progress to MRI-guided extremely hypofractionated treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Background and Purpose: Recently, intermediate and high-risk prostate cancer patients have been treated in a multicenter phase II trial with extremely hypofractionated prostate radiotherapy (hypo-FLAME trial). The purpose of the current study was to investigate whether a 1.5 T magnetic resonance imaging guided linear accelerator (MRI-linac) could achieve complex dose distributions of a quality similar to conventional linac state-of-the-art prostate treatments., Materials and Methods: The clinically delivered treatment plans of 20 hypo-FLAME patients (volumetric modulated arc therapy, 10 MV, 5 mm leaf width) were included. Prescribed dose to the prostate was 5 × 7 Gy, with a focal tumor boost up to 5 × 10 Gy. MRI-linac treatment plans (intensity modulated radiotherapy, 7 MV, 7 mm leaf width, fixed collimator angle and 1.5 T magnetic field) were calculated. Dose distributions were compared., Results: In both conventional and MRI-linac treatment plans, the V35Gy to the whole prostate was >99% in all patients. Mean dose to the gross tumor volume was 45 Gy for conventional and 44 Gy for MRI-linac plans, respectively. Organ at risk doses were met in the majority of plans, except for a rectal V35Gy constraint, which was exceeded in one patient, by 1 cc, for both modalities. The bladder V32Gy and V28Gy constraints were exceeded in two and one patient respectively, for both modalities., Conclusion: Planning of stereotactic radiotherapy with focal ablative boosting in prostate cancer on a high field MRI-linac is feasible with the current MRI-linac properties, without deterioration of plan quality compared to conventional treatments., (© 2019 The Authors.)

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods., Materials and Methods: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured., Results: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases., Conclusion: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.