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Research in the field of local and locoregional breast cancer radiotherapy aims to maintain excellent oncological outcomes while reducing treatment-related toxicity. Adaptive radiotherapy (ART) considers variations in target and organs at risk (OARs) anatomy occurring during the treatment course and integrates these in re-optimized treatment plans. Exploiting ART routinely in clinic may result in smaller target volumes and better OAR sparing, which may lead to reduction of acute as well as late toxicities. In this review MR-guided and CT-guided ART for breast cancer patients according to different clinical scenarios (neoadjuvant and adjuvant partial breast irradiation, whole breast, chest wall and regional nodal irradiation) are reviewed and their advantages as well as challenging aspects discussed.

Introduction: The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary. Material and Methods: To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated. Results: Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild. Conclusion: The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus.

Introduction: Stereotactic body radiotherapy (SBRT) is an established ablative treatment for liver tumors with excellent local control rates. Magnetic resonance imaging guided radiotherapy (MRgRT) provides superior soft tissue contrast and may therefore facilitate a marker-less liver SBRT workflow. The goal of the present study was to investigate feasibility, workflow parameters, toxicity and patient acceptance of MRgSBRT on a 1.5 T MR-Linac. Methods: Ten consecutive patients with liver metastases treated on a 1.5 T MR-Linac were included in this prospective trial. Tumor delineation was performed on four-dimensional computed tomography scans and both exhale triggered and free-breathing T2 MRI scans from the MR-Linac. An internal target volume based approach was applied. Organ at risk constraints were based on the UKSABR guidelines (Version 6.1). Patient acceptance regarding device specific aspects was assessed and toxicity was scored according to the common toxicity criteria of adverse events, version 5. Results: Nine of ten tumors were clearly visible on the 1.5 T MR-Linac. No patient had fiducial markers placed for treatment. All patients were treated with three or five fractions. Median dose to 98% of the gross tumor volume was 38.5 Gy. The median time from “patient identity check” until “beam-off” was 31 min. Median beam on time was 9.6 min. Online MRgRT was well accepted in general and no treatment had to be interrupted on patient request. No event of symptomatic radiation induced liver disease was observed after a median follow-up of ten month (range 3–17 months). Conclusion: Our early experience suggests that online 1.5 T MRgSBRT of liver metastases represents a promising new non-invasive marker-free treatment modality based on high image quality, clinically reasonable in-room times and high patient acceptance. Further studies are necessary to assess clinical outcome, to validate advanced motion management and to explore the benefit of online response adaptive liver SBRT.

Combined PET/MRI may be highly beneficial for radiotherapy treatment planning in terms of tumor delineation and characterization. To standardize tumor volume delineation, an automatic algorithm for the co-segmentation of head and neck (HN) tumors based on PET/MR data was developed. Ten HN patient datasets acquired in a combined PET/MR system were available for this study. The proposed algorithm uses both the anatomical T2-weighted MR and FDG-PET data. For both imaging modalities tumor probability maps were derived, assigning each voxel a probability of being cancerous based on its signal intensity. A combination of these maps was subsequently segmented using a threshold level set algorithm. To validate the method, tumor delineations from three radiation oncologists were available. Inter-observer variabilities and variabilities between the algorithm and each observer were quantified by means of the Dice similarity index and a distance measure. Inter-observer variabilities and variabilities between observers and algorithm were found to be comparable, suggesting that the proposed algorithm is adequate for PET/MR co-segmentation. Moreover, taking into account combined PET/MR data resulted in more consistent tumor delineations compared to MR information only. [ABSTRACT FROM AUTHOR]

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 D2cm 3 (2.8 Gy), duodenum Dmax (7.1 Gy), and rectum D0.5cm 3 (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., Competing Interests: MM and DT report institutional collaborations including financial and non-financial support by Elekta AB, Philips, TheraPanacea, Dr. Sennewald, Brainlab and PTW Freiburg. MM acknowledges funding through the German Research Council (DFG), grants no. MU 4603/1-1 (PAK997/1) and ZI 736/2-1. HZ is partly supported by the grant R01-EB028324 from National Institute of Biomedical Imaging andBioengineering, NIH. All other authors do not declare financial interests/personal relationships., (© 2024 The Author(s).)

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Background and Purpose: MR-guided radiotherapy (MRgRT) online plan adaptation accounts for tumor volume changes, interfraction motion and thus allows daily sparing of relevant organs at risk. Due to the high interfraction variability of bladder and rectum, patients with tumors in the pelvic region may strongly benefit from adaptive MRgRT. Currently, fast automatic annotation of anatomical structures is not available within the online MRgRT workflow. Therefore, the aim of this study was to train and validate a fast, accurate deep learning model for automatic MRI segmentation at the MR-Linac for future implementation in a clinical MRgRT workflow., Materials and Methods: For a total of 47 patients, T2w MRI data were acquired on a 1.5 T MR-Linac (Unity, Elekta) on five different days. Prostate, seminal vesicles, rectum, anal canal, bladder, penile bulb, body and bony structures were manually annotated. These training data consisting of 232 data sets in total was used for the generation of a deep learning based autocontouring model and validated on 20 unseen T2w-MRIs. For quantitative evaluation the validation set was contoured by a radiation oncologist as gold standard contours (GSC) and compared in MATLAB to the automatic contours (AIC). For the evaluation, dice similarity coefficients (DSC), and 95% Hausdorff distances (95% HD), added path length (APL) and surface DSC (sDSC) were calculated in a caudal-cranial window of ± 4 cm with respect to the prostate ends. For qualitative evaluation, five radiation oncologists scored the AIC on the possible usage within an online adaptive workflow as follows: (1) no modifications needed, (2) minor adjustments needed, (3) major adjustments/ multiple minor adjustments needed, (4) not usable., Results: The quantitative evaluation revealed a maximum median 95% HD of 6.9 mm for the rectum and minimum median 95% HD of 2.7 mm for the bladder. Maximal and minimal median DSC were detected for bladder with 0.97 and for penile bulb with 0.73, respectively. Using a tolerance level of 3 mm, the highest and lowest sDSC were determined for rectum (0.94) and anal canal (0.68), respectively. Qualitative evaluation resulted in a mean score of 1.2 for AICs over all organs and patients across all expert ratings. For the different autocontoured structures, the highest mean score of 1.0 was observed for anal canal, sacrum, femur left and right, and pelvis left, whereas for prostate the lowest mean score of 2.0 was detected. In total, 80% of the contours were rated be clinically acceptable, 16% to require minor and 4% major adjustments for online adaptive MRgRT., Conclusion: In this study, an AI-based autocontouring was successfully trained for online adaptive MR-guided radiotherapy on the 1.5 T MR-Linac system. The developed model can automatically generate contours accepted by physicians (80%) or only with the need of minor corrections (16%) for the irradiation of primary prostate on the clinically employed sequences., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors report institutional collaborations with TheraPanacea, Elekta, Philips, Kaiku and PTW Freiburg which provided technical and/or financial support. TheraPanacea developed the proposed model, but were not involved in the analysis and scoring of the testing dataset.], (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background and Purpose: For dosimetry in magnetic resonance (MR) guided radiotherapy, assessing the magnetic field correction factors of air-vented ionization chambers is crucial. Novel MR-optimized chambers reduce MR-imaging artefacts, enhancing their quality assurance utility. This study aimed to characterize two new MR-optimized ionization chambers with sensitive volumes of 0.07 and 0.016 cm 3 regarding magnetic field correction factors and intra-type variation and compare them to their conventional counterparts., Material and Methods: Five chambers of each type were evaluated in a water phantom, using a clinical linear accelerator and an electromagnet, as well as a 1.5 T MR-linac system. The magnetic field correction factor k B → , Q , addressing the change of response caused by a magnetic field, was assessed together with its intra-type variation. MR-optimized and conventional chambers were compared using a Mann-Whitney U-Test., Results: Considering 1.5 T and a perpendicular chamber orientation, we observed significant differences in the magnetic field-induced change in chamber reading between the two 0.016 cm 3 chamber versions (p = 0.03). For a 7 MV beam, MR-optimized chambers (0.016/0.07 cm 3 ) showed k B → , Q values of 1.0426(66) and 1.0463(44), compared to 1.0319(53) and 1.0480(41) of their conventional counterparts. In anti-parallel orientation, k B → , Q was 1.0012(69) and 0.9863(49) for the MR-optimized chambers. The average intra-type variation of k B → , Q over all chamber types was 0.3%., Conclusion: Magnetic field correction factors were successfully determined for four ionization chamber types, including two new MR-optimized versions, allowing their use in MR-linac absolute dosimetry. Evaluation of the intra-type variation enabled the assessment of their contribution to the uncertainty of tabulated k B → , Q ., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Department of Radiation Oncology Tübingen receives financial and technical support by Elekta, Philips, Siemens, Dr. Sennewald Medizintechnik, Kaiku Health, TheraPanacea, PTW and ITV in the context of research cooperations., (© 2024 The Authors.)

Background and Purpose: Before quantitative imaging biomarkers (QIBs) acquired with magnetic resonance imaging (MRI) can be used for interventional trials in radiotherapy (RT), technical validation of these QIBs is necessary. The aim of this study was to assess the reproducibility of apparent diffusion coefficient (ADC) values, derived from diffusion-weighted (DW) MRI, in head and neck cancer using a 1.5 T MR-Linac (MRL) by comparison to a 3 T diagnostic scanner (DS)., Material and Methods: DW-MRIs were acquired on MRL and DS for 15 head and neck cancer patients before RT and in week 2 and rigidly registered to the planning computed tomography. Mean ADC values were calculated for submandibular (SG) and parotid (PG) glands as well as target volumes (TV, gross tumor volume and lymph nodes), which were delineated based on computed tomography. Mean absolute ADC differences as well as within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs) were calculated for all volumes of interest., Results: A total of 23 datasets were analyzed. Mean ADC difference (DS-MRL) for SG, PG and TV resulted in 142, 254 and 93·10 -6 mm 2 /s. wCVs/ICCs, comparing MRL and DS, were determined as 13.7 %/0.26, 24.4 %/0.23 and 16.1 %/0.73 for SG, PG and TV, respectively., Conclusion: ADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT., 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.)

Background and Purpose: Daily online treatment plan adaptation requires a fast workflow and planning process. Current online planning consists of adaptation of a predefined reference plan, which might be suboptimal in cases of large anatomic changes. The aim of this study was to investigate plan quality differences between the current online re-planning approach and a complete re-optimization., Material and Methods: Magnetic resonance linear accelerator reference plans for ten prostate cancer patients were automatically generated using particle swarm optimization (PSO). Adapted plans were created for each fraction using (1) the current re-planning approach and (2) full PSO re-optimization and evaluated overall compliance with institutional dose-volume criteria compared to (3) clinically delivered fractions. Relative volume differences between reference and daily anatomy were assessed for planning target volumes (PTV60, PTV57.6), rectum and bladder and correlated with dose-volume results., Results: The PSO approach showed significantly higher adherence to dose-volume criteria than the reference approach and clinical fractions (p < 0.001). In 74 % of PSO plans at most one criterion failed compared to 56 % in the reference approach and 41 % in clinical plans. A fair correlation between PTV60 D98% and relative bladder volume change was observed for the reference approach. Bladder volume reductions larger than 50 % compared to the reference plan recurrently decreased PTV60 D98% below 56 Gy., Conclusion: Complete re-optimization maintained target coverage and organs at risk sparing even after large anatomic variations. Re-planning based on daily magnetic resonance imaging was sufficient for small variations, while large variations led to decreasing target coverage and organ-at-risk sparing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Department of Radiation Oncology Tübingen receives within the frame of research agreements financial and technical support as well as sponsoring for travels and scientific symposia from Elekta AB (Stockholm, Sweden), TheraPanacea (Paris, France), Philips GmbH (Best, The Netherlands); Dr. Sennewald Medizintechnik GmbH (Munich, Germany), PTW (Freiburg, Germany), Siemens (Munich, Germany) and Kaiku Health (Helsinki, Finland)., (© 2024 The Author(s).)

Magnetic resonance imaging-guided radiation therapy (MRIgRT) has improved soft tissue contrast over computed tomography (CT) based image-guided RT. Superior visualization of the target and surrounding radiosensitive structures has the potential to improve oncological outcomes partly due to safer dose-escalation and adaptive planning. In this review, we highlight the workflow of adaptive MRIgRT planning, which includes simulation imaging, daily MRI, identifying isocenter shifts, contouring, plan optimization, quality control, and delivery. Increased utilization of MRIgRT will depend on addressing technical limitations of this technology, while addressing treatment efficacy, cost-effectiveness, and workflow training., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept., Materials and Methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans., Results: Median NTCP of the reference plan (NTCP ref ) and of the experimental plan (NTCP ex ) were 0.24 (range 0.11-0.29) and 0.42 (range 0.18-0.54), respectively. NTCP ex was a median of 1.77 (range 1.60-1.99) times as high as the NTXP ref . In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66-2.35). The defined constraints for the organs at risk were feasible., Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible., 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).)

Background: Target volume definition for curative radiochemotherapy in head and neck cancer is crucial since the predominant recurrence pattern is local. Additional diagnostic imaging like MRI is increasingly used, yet it is usually hampered by different patient positioning compared to radiotherapy. In this study, we investigated the impact of diagnostic MRI in treatment position for target volume delineation., Methods: We prospectively analyzed patients who were suitable and agreed to undergo an MRI in treatment position with immobilization devices prior to radiotherapy planning from 2017 to 2019. Target volume delineation for the primary tumor was first performed using all available information except for the MRI and subsequently with additional consideration of the co-registered MRI. The derived volumes were compared by subjective visual judgment and by quantitative mathematical methods., Results: Sixteen patients were included and underwent the planning CT, MRI and subsequent definitive radiochemotherapy. In 69% of the patients, there were visually relevant changes to the gross tumor volume (GTV) by use of the MRI. In 44%, the GTV&#95;MRI would not have been covered completely by the planning target volume (PTV) of the CT-only contour. Yet, median Hausdorff und DSI values did not reflect these differences. The 3-year local control rate was 94%., Conclusions: Adding a diagnostic MRI in RT treatment position is feasible and results in relevant changes in target volumes in the majority of patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck cancers (HNC) but requires extensive validation. We performed technical validation to compare six total DWI sequences on an MR-linac and MR simulator (MR sim) in patients, volunteers, and phantoms., Methods: Ten human papillomavirus-positive oropharyngeal cancer patients and ten healthy volunteers underwent DWI on a 1.5 T MR-linac with three DWI sequences: echo planar imaging (EPI), split acquisition of fast spin echo signals (SPLICE), and turbo spin echo (TSE). Volunteers were also imaged on a 1.5 T MR sim with three sequences: EPI, BLADE (vendor tradename), and readout segmentation of long variable echo trains (RESOLVE). Participants underwent two scan sessions per device and two repeats of each sequence per session. Repeatability and reproducibility within-subject coefficient of variation (wCV) of mean ADC were calculated for tumors and lymph nodes (patients) and parotid glands (volunteers). ADC bias, repeatability/reproducibility metrics, SNR, and geometric distortion were quantified using a phantom., Results: In vivo repeatability/reproducibility wCV for parotids were 5.41%/6.72%, 3.83%/8.80%, 5.66%/10.03%, 3.44%/5.70%, 5.04%/5.66%, 4.23%/7.36% for EPI MR-linac , SPLICE, TSE, EPI MR sim , BLADE, RESOLVE. Repeatability/reproducibility wCV for EPI MR-linac , SPLICE, TSE were 9.64%/10.28%, 7.84%/8.96%, 7.60%/11.68% for tumors and 7.80%/9.95%, 7.23%/8.48%, 10.82%/10.44% for nodes. All sequences except TSE had phantom ADC biases within ± 0.1x10 -3 mm 2 /s for most vials (EPI MR-linac , SPLICE, and BLADE had 2, 3, and 1 vials out of 13 with larger biases, respectively). SNR of b = 0 images was 87.3, 180.5, 161.3, 171.0, 171.9, 130.2 for EPI MR-linac , SPLICE, TSE, EPI MR sim , BLADE, RESOLVE., Conclusion: MR-linac DWI sequences demonstrated near-comparable performance to MR sim sequences and warrant further clinical validation for treatment response assessment in HNC., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Tumor hypoxia and other microenvironmental factors are key determinants of treatment resistance. Hypoxia positron emission tomography (PET) and functional magnetic resonance imaging (MRI) are established prognostic imaging modalities to identify radiation resistance in head-and-neck cancer (HNC). The aim of this preclinical study was to develop a multi-parametric imaging parameter specifically for focal radiotherapy (RT) dose escalation using HNC xenografts of different radiation sensitivities., Methods: A total of eight human HNC xenograft models were implanted into 68 immunodeficient mice. Combined PET/MRI using dynamic [18F]-fluoromisonidazole (FMISO) hypoxia PET, diffusion-weighted (DW), and dynamic contrast-enhanced MRI was carried out before and after fractionated RT (10 × 2 Gy). Imaging data were analyzed on voxel-basis using principal component (PC) analysis for dynamic data and apparent diffusion coefficients (ADCs) for DW-MRI. A data- and hypothesis-driven machine learning model was trained to identify clusters of high-risk subvolumes (HRSs) from multi-dimensional (1-5D) pre-clinical imaging data before and after RT. The stratification potential of each 1D to 5D model with respect to radiation sensitivity was evaluated using Cohen's d-score and compared to classical features such as mean/peak/maximum standardized uptake values (SUV mean/peak/max ) and tumor-to-muscle-ratios (TMR peak/max ) as well as minimum/valley/maximum/mean ADC., Results: Complete 5D imaging data were available for 42 animals. The final preclinical model for HRS identification at baseline yielding the highest stratification potential was defined in 3D imaging space based on ADC and two FMISO PCs ([Formula: see text]). In 1D imaging space, only clusters of ADC revealed significant stratification potential ([Formula: see text]). Among all classical features, only ADC valley showed significant correlation to radiation resistance ([Formula: see text]). After 2 weeks of RT, FMISO&#95;c1 showed significant correlation to radiation resistance ([Formula: see text])., Conclusion: A quantitative imaging metric was described in a preclinical study indicating that radiation-resistant subvolumes in HNC may be detected by clusters of ADC and FMISO using combined PET/MRI which are potential targets for future functional image-guided RT dose-painting approaches and require clinical validation., (© 2023. The Author(s).)

Background: Hybrid MRI linear accelerators (MR-Linac) might enable individualized online adaptation of radiotherapy using quantitative MRI sequences as diffusion-weighted imaging (DWI). The purpose of this study was to investigate the dynamics of lesion apparent diffusion coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiation therapy (MRgRT) on a 1.5T MR-Linac. The ADC values at a diagnostic 3T MRI scanner were used as the reference standard., Patients and and Methods: In this prospective single-center study, patients with biopsy-confirmed prostate cancer who underwent both an MRI exam at a 3T scanner (MRI 3T ) and an exam at a 1.5T MR-Linac (MRL) at baseline and during radiotherapy were included. Lesion ADC values were measured by a radiologist and a radiation oncologist on the slice with the largest lesion. ADC values were compared before vs . during radiotherapy (during the second week) on both systems via paired t-tests. Furthermore, Pearson correlation coefficient and inter-reader agreement were computed., Results: A total of nine male patients aged 67 ± 6 years [range 60 - 67 years] were included. In seven patients, the cancerous lesion was in the peripheral zone, and in two patients the lesion was in the transition zone. Inter-reader reliability regarding lesion ADC measurement was excellent with an intraclass correlation coefficient of (ICC) > 0.90 both at baseline and during radiotherapy. Thus, the results of the first reader will be reported. In both systems, there was a statistically significant elevation of lesion ADC during radiotherapy (mean MRL-ADC at baseline was 0.97 ± 0.18 × 10 -3 mm 2 /s vs . mean MRL-ADC during radiotherapy 1.38 ± 0.3 × 10 -3 mm 2 /s, yielding a mean lesion ADC elevation of 0.41 ± 0.20 × 10 -3 mm 2 /s, p < 0.001). Mean MRI 3T -ADC at baseline was 0.78 ± 0.165 × 10 -3 mm 2 /s vs . mean MRI 3T -ADC during radiotherapy 0.99 ± 0.175 × 10 -3 mm 2 /s, yielding a mean lesion ADC elevation of 0.21 ± 0.96 × 10 -3 mm 2 /s p < 0.001). The absolute ADC values from MRL were consistently significantly higher than those from MRI 3T at baseline and during radiotherapy (p < = 0.001). However, there was a strong positive correlation between MRL-ADC and MRI 3T -ADC at baseline ( r = 0.798, p = 0.01) and during radiotherapy ( r = 0.863, p = 0.003)., Conclusions: Lesion ADC as measured on MRL increased significantly during radiotherapy and ADC measurements of lesions on both systems showed similar dynamics. This indicates that lesion ADC as measured on the MRL may be used as a biomarker for evaluation of treatment response. In contrast, absolute ADC values as calculated by the algorithm of the manufacturer of the MRL showed systematic deviations from values obtained on a diagnostic 3T MRI system. These preliminary findings are promising but need large-scale validation. Once validated, lesion ADC on MRL might be used for real-time assessment of tumor response in patients with prostate cancer undergoing MR-guided radiation therapy., (© 2023 Haidara Almansour et al., published by Sciendo.)

Background: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC., Methods: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival., Discussion: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques., Trial Registration: ClinicalTrials.gov: NCT05237453 ., (© 2023. The Author(s).)

Objective: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system., Materials and Methods: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning., Results: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning., Conclusions: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems., 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. Published by Elsevier B.V.)

Purpose: To test soy lecithin as a substance added to water for the construction of MRI phantoms with tissue-like diffusion coefficients. The performance of soy lecithin was assessed for the useable range of adjustable ADC values, the degree of non-Gaussian diffusion, simultaneous effects on relaxation times, and spectral signal properties., Methods: Aqueous soy lecithin solutions of different concentrations (0%, 0.5%, 1%, 2%, 3% …, 10%) and soy lecithin-agar gels were prepared and examined on a 3 Tesla clinical scanner at 18.5° ± 0.5°C. Echoplanar sequences (b values: 0-1000/3000 s/mm 2 ) were applied for ADC measurements. Quantitative relaxometry and MRS were performed for assessment of T 1 , T 2 , and detectable spectral components., Results: The presence of soy lecithin significantly restricts the diffusion of water molecules and mimics the nearly Gaussian nature of diffusion observed in tissue (for b values <1000 s/mm 2 ). ADC values ranged from 2.02 × 10 -3  mm 2 /s to 0.48 × 10 -3  mm 2 /s and cover the entire physiological range reported on biological tissue. Measured T 1 /T 2 values of pure lecithin solutions varied from 2685/2013 to 668/133 ms with increasing concentration. No characteristic signals of soy lecithin were observed in the MR spectrum. The addition of agar to the soy lecithin solutions allowed T 2 values to be well adjusted to typical values found in parenchymal tissue without affecting the soy lecithin-controlled ADC value., Conclusion: Soy lecithin is a promising substance for the construction of diffusion phantoms with tissue-like ADC values. It provides several advantages over previously proposed substances, in particular a wide range of adjustable ADC values, the lack of additional 1 H-signals, and the possibility to adjust ADC and T 2 values (by adding agar) almost independently of each other., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

PET/CT imaging plays an increasing role in radiotherapy treatment planning. The aim of this article was to identify the major use cases and technical as well as medical physics challenges during integration of these data into treatment planning. Dedicated aspects, such as (i) PET/CT-based radiotherapy simulation, (ii) PET-based target volume delineation, (iii) functional avoidance to optimized organ-at-risk sparing and (iv) functionally adapted individualized radiotherapy are discussed in this article. Furthermore, medical physics aspects to be taken into account are summarized and presented in form of check-lists., 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. Published by Elsevier GmbH.)

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., Competing Interests: MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Centers both have master research agreements with Elekta AB and Philips Healthcare. CF has received direct industry grant support, speaking honoraria, and travel funding from Elekta AB. KB received funding from RaySearch Laboratories AB through a Co-Development and Collaboration Agreement. KB has a licensing agreement with RaySearch Laboratories AB. NT has received travel funding and speaking honoraria from Elekta and Philips. DT reports institutional collaborations including financial and non-financial support by Elekta, Philips, Kaiku, Therapanacea and PTW Freiburg. JC and EB-R are employees of Elekta AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 McDonald, Zachiu, Christodouleas, Naser, Ruschin, Sonke, Thorwarth, Létourneau, Tyagi, Tadic, Yang, Li, Bernchou, Hyer, Snyder, Bubula-Rehm, Fuller and Brock.)

Introduction: Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life., Material and Methods: Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used., Results: A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data., Conclusion: Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing., Competing Interests: The Department of Radiation Oncology Tübingen receives within the frame of research agreements financial and technical support as well as sponsoring for travels and scientific symposia from: Elekta AB Stockholm, Sweden, Philips, Siemens, Dr. Sennewald Medizintechnik, Kaiku Health, TheraPanacea, PTW, ITV. CG, SB: Travel costs by Elekta AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Uder, Nachbar, Butzer, Boldt, Baumeister, Bitzer, Königsrainer, Seufferlein, Hoffmann, Gatidis, Nikolaou, Zips, Thorwarth, Gani and Boeke.)