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This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections., 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., (© 2024 The Author(s).)

Background and Purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC., Materials and Methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes., Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%., Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors acknowledge funding by the Dutch Research Council (NWO) through Project No. 18495 (ADEQUATE)., (© 2024 The Authors.)

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.)

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.

Background and Purpose: Manual contouring of neurovascular structures on prostate magnetic resonance imaging (MRI) is labor-intensive and prone to considerable interrater disagreement. Our aim is to contour neurovascular structures automatically on prostate MRI by deep learning (DL) to improve workflow and interrater agreement., Materials and Methods: Segmentation of neurovascular structures was performed on pre-treatment 3.0 T MRI data of 131 prostate cancer patients (training [n = 105] and testing [n = 26]). The neurovascular structures include the penile bulb (PB), corpora cavernosa (CCs), internal pudendal arteries (IPAs), and neurovascular bundles (NVBs). Two DL networks, nnU-Net and DeepMedic, were trained for auto-contouring on prostate MRI and evaluated using volumetric Dice similarity coefficient (DSC), mean surface distances (MSD), Hausdorff distances, and surface DSC. Three radiation oncologists evaluated the DL-generated contours and performed corrections when necessary. Interrater agreement was assessed and the time required for manual correction was recorded., Results: nnU-Net achieved a median DSC of 0.92 (IQR: 0.90-0.93) for the PB, 0.90 (IQR: 0.86-0.92) for the CCs, 0.79 (IQR: 0.77-0.83) for the IPAs, and 0.77 (IQR: 0.72-0.81) for the NVBs, which outperformed DeepMedic for each structure (p < 0.03). nnU-Net showed a median MSD of 0.24 mm for the IPAs and 0.71 mm for the NVBs. The median interrater DSC ranged from 0.93 to 1.00, with the majority of cases (68.9%) requiring manual correction times under two minutes., Conclusions: DL enables reliable auto-contouring of neurovascular structures on pre-treatment MRI data, easing the clinical workflow in neurovascular-sparing MR-guided radiotherapy., 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., (© 2023 The Author(s).)

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.)

Background: Intrafraction motion during radiotherapy limits margin reduction and dose escalation. Magnetic resonance (MR)-guided linear accelerators (MR-Linac) have emphasised this issue by enabling intrafraction imaging. We present and clinically apply a new workflow to counteract systematic intrafraction motion during MR-guided stereotactic body radiotherapy (SBRT)., Materials and Methods: With the sub-fractionation workflow, the daily dose is delivered in multiple sequential parts (sub-fractions), each adapted to the latest anatomy. As each sub-fractionation treatment plan complies with the dose constraints, no online dose accumulation is required. Imaging and treatment planning are executed in parallel with dose delivery to minimise dead time, enabling an efficient workflow. The workflow was implemented on a 1.5 T MR-Linac and applied in 15 prostate cancer (PCa) patients treated with 5 × 7.25 Gy in two sub-fractions of 3.625 Gy (10 × 3.625 Gy in total). Intrafraction clinical target volume (CTV) motion was determined and compared to a workflow with single-plan delivery. Furthermore, required planning target volume (PTV) margins were determined., Results: Average on-table time was 42.7 min. Except for two fractions, all fractions were delivered within 60 min. Average intrafraction 3D CTV displacement (±standard deviation) was 1.1 mm (± 0.7) with the sub-fractionation workflow, whereas this was up to 3.5 mm (± 2.4) without sub-fractionation. Calculated PTV margins required with sub-fractionation were 1.0 mm (left-right), 2.4 mm (cranial-caudal), and 2.6 mm (anterior-posterior)., Conclusion: Feasibility of the sub-fractionation workflow was demonstrated in 15 PCa patients treated with two sub-fractions on a 1.5 T MR-Linac. The workflow allows for significant PTV margin reduction in these patients by reducing systematic intrafraction motion during SBRT., 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 © 2022 The Author(s). Published by Elsevier B.V. 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: Focal dose escalation in external beam radiotherapy (EBRT) showed an increase in 5-yr biochemical disease-free survival in the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial., Objective: To analyze the effect of a focal boost to intraprostatic lesions on local failure-free survival (LFS) and regional + distant metastasis-free survival (rdMFS)., Design, Setting, and Participants: Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial., Intervention: Standard treatment of 77 Gy to the entire prostate in 35 fractions was compared to an additional boost to the macroscopic tumor of up to 95 Gy during EBRT., Outcome Measurements and Statistical Analysis: LFS and rdMFS, measured via any type of imaging, were compared between the treatment arms using Kaplan-Meier and Cox regression analyses. Dose-response curves were created for local failure (LF) and regional + distant metastatic failure (rdMF) using logistic regression., Results and Limitations: A total of 571 patients were included in the FLAME trial. Over median follow-up of 72 mo (interquartile range 58-86), focal boosting decreased LF (hazard ratio [HR] 0.33, 95% confidence interval [CI] 0.14-0.78) and rdMF (HR 0.58, 95% CI 0.35-0.93). Dose-response curves showed that a greater dose to the tumor resulted in lower LF and rdMF rates., Conclusions: A clear dose-response relation for LF and rdMF was observed, suggesting that adequate focal dose escalation to intraprostatic lesions prevents undertreatment of the primary tumor, resulting in an improvement rdMF., Patient Summary: Radiotherapy is a treatment option for high-risk prostate cancer. The FLAME trial has shown that a high dose specifically targeted at the tumor within the prostate will result in better disease outcome, with less likelihood of regional and distant disease spread. The FLAME trial is registered on ClinicalTrials.gov as NCT01168479., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Magnetic resonance (MR)-guided linear accelerators (MR-Linac) enable accurate estimation of delivered doses through dose accumulation using daily MR images and treatment plans. We aimed to assess the association between the accumulated bladder (wall) dose and patient-reported acute urinary toxicity in prostate cancer (PCa) patients treated with stereotactic body radiation therapy (SBRT)., Materials and Methods: One-hundred-and-thirty PCa patients treated on a 1.5 T MR-Linac were included. Patients filled out International Prostate Symptom Scores (IPSS) questionnaires at baseline, 1 month, and 3 months post-treatment. Deformable image registration-based dose accumulation was performed to reconstruct the delivered dose. Dose parameters for both bladder and bladder wall were correlated with a clinically relevant increase in IPSS (≥ 10 points) and/or start of alpha-blockers within 3 months using logistic regression., Results: Thirty-nine patients (30%) experienced a clinically relevant IPSS increase and/or started with alpha-blockers. Bladder D5cm 3 , V 10-35Gy (in %), and D mean and Bladder wall V 10-35Gy (cm 3 and %) and D mean were correlated with the outcome (odds ratios 1.04-1.33, p-values 0.001-0.044). Corrected for baseline characteristics, bladder V 10-35Gy (in %) and D mean and bladder wall V 10-35Gy (cm 3 and %) and D mean were still correlated with the outcome (odds ratios 1.04-1.30, p-values 0.001-0.028). Bladder wall parameters generally showed larger AUC values., Conclusion: This is the first study to assess the correlation between accumulated bladder wall dose and patient-reported urinary toxicity in PCa patients treated with MR-guided SBRT. The dose to the bladder wall is a promising parameter for prediction of patient-reported urinary toxicity and therefore warrants prospective validation and consideration in treatment planning., 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 © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose or Objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort., Material and Methods: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated., Results: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm 3 and urethra D0.1 cm 3 , with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed., Conclusion: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer., Competing Interests: Conflict of interest statement All authors declare having no conflict of interest related to the content of this manuscript., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

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).)