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Background and purpose: Conventional image-guided radiotherapy (conv-IGRT) is standard in prostate cancer (PC) but does not account for inter-fraction anatomical changes. Online-adaptive magnetic resonance-guided RT (OA-MRgRT) may improve organ-at-risk (OARs) sparing and clinical target volume (CTV) coverage. The aim of this study was to analyze accumulated OAR and target doses in PC after OA-MRgRT and conv-IGRT in comparison to pre-treatment reference planning (refPlan). Material and methods: Ten patients with PC, previously treated with OA-MRgRT at the 1.5 T MR-Linac (20x3Gy), were included. Accumulated OA-MRgRT doses were determined by deformably registering all fraction’s MR-images. Conv-IGRT was simulated through rigid registration of the planning computed tomography with each fraction’s MR-image for dose mapping/accumulation. Dose-volume parameters (DVPs), including CTV D50% and D98%, rectum, bladder, urethra, Dmax and V56Gy for OA-MRgRT, conv-IGRT and refPlan were compared using the Wilcoxon signed-rank test. Clinical relevance of accumulated dose differences was analyzed using a normal-tissue complication-probability model. Results: CTV-DVPs were comparable, whereas OA-MRgRT yielded decreased median OAR-DVPs compared to conv-IGRT, except for bladder V56Gy. OA-MRgRT demonstrated significantly lower median rectum Dmax over conv-IGRT (59.1/59.9 Gy, p = 0.006) and refPlan (60.1 Gy, p = 0.012). Similarly, OA-MRgRT yielded reduced median bladder Dmax compared to conv-IGRT (60.0/60.4 Gy, p = 0.006), and refPlan (61.2 Gy, p = 0.002). Overall, accumulated dose differences were small and did not translate into clinically relevant effects. Conclusion: Deformably accumulated OA-MRgRT using 20x3Gy in PC showed significant but small dosimetric differences comparted to conv-IGRT. Feasibility of a dose accumulation methodology was demonstrated, which may be relevant for evaluating future hypo-fractionated OA-MRgRT approaches.

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.

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

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 (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11–0.29) and 0.42 (range 0.18–0.54), respectively. NTCPex was a median of 1.77 (range 1.60–1.99) times as high as the NTXPref. 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.

Abstract 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_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.

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 cm3 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 kB→,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 cm3 chamber versions (p = 0.03). For a 7 MV beam, MR-optimized chambers (0.016/0.07 cm3) showed kB→,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, kB→,Q was 1.0012(69) and 0.9863(49) for the MR-optimized chambers. The average intra-type variation of kB→,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 kB→,Q.

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

Abstract 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 .

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.

Background: Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes. Methods: Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers’ delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated. Results: Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p

Introduction: Non-surgical management of rectal cancer aiming for organ-preservation is an important development to improve rectal cancer treatment. Dose escalated radiotherapy represents one approach to increase clinical complete response (cCR) rates. In the present study we present feasibility and outcome data on rectal cancer patients who were treated with dose escalated radiotherapy using an MR guided online response-adaptive workflow. Material and methods: A total of five patients were treated with 45 Gy in 25 fractions to the mesorectum and the internal iliac lymph nodes and a simultaneous integrated boost to the primary tumor with 50 Gy in 25 fractions on a conventional linac. In addition, weekly response-adaptive boost fractions with 3 Gy per fraction were scheduled on a 1.5 T MR-Linac. Concomitant chemotherapy with 5-fluorouracil was given as continuous venous infusion during the first and last week of treatment. Response was evaluated approximately-three months after the end of treatment and surgery was omitted in case of a clinical complete response (cCR) or a near cCR. Toxicity was graded by using PRO-CTCAE, Quality of life by the EORTC-QLQ-C30 questionnaire and continence according to the Wexner scale. Results: Response-adaptive dose escalated radiotherapy was feasible and well tolerated by all patients. Four reached a clinical complete response, one had a local excision confirming pathological complete response (pCR). All PRO-CTCAE grade 3 toxicities resolved within six months after the end of treatment. Quality of life and continence scores during follow-up were comparable to baseline levels. Conclusion: Dose-escalated online response-adaptive MR-guided radiotherapy appears to be a very promising treatment with the goal of organ preservation in rectal cancer leading to high response rates, excellent organ function and limited side effects. Further prospective evaluation is needed.

Abstract Background To report on the discriminative ability of a simulation Computed Tomography (CT)-based radiomics signature for predicting response to treatment in patients undergoing neoadjuvant chemo-radiation for locally advanced adenocarcinoma of the rectum. Methods Consecutive patients treated at the Universities of Tübingen (from 1/1/07 to 31/12/10, explorative cohort) and Florence (from 1/1/11 to 31/12/17, external validation cohort) were considered in our dual-institution, retrospective analysis. Long-course neoadjuvant chemo-radiation was performed according to local policy. On simulation CT, the rectal Gross Tumor Volume was manually segmented. A feature selection process was performed yielding mineable data through an in-house developed software (written in Python 3.6). Model selection and hyper-parametrization of the model was performed using a fivefold cross validation approach. The main outcome measure of the study was the rate of pathologic good response, defined as the sum of Tumor regression grade (TRG) 3 and 4 according to Dworak’s classification. Results Two-hundred and one patients were included in our analysis, of whom 126 (62.7%) and 75 (37.3%) cases represented the explorative and external validation cohorts, respectively. Patient characteristics were well balanced between the two groups. A similar rate of good response to neoadjuvant treatment was obtained in in both cohorts (46% and 54.7%, respectively; p = 0.247). A total of 1150 features were extracted from the planning scans. A 5-metafeature complex consisting of Principal component analysis (PCA)-clusters (whose main components are LHL Grey-Level-Size-Zone: Large Zone Emphasis, Elongation, HHH Intensity Histogram Mean, HLL Run-Length: Run Level Variance and HHH Co-occurence: Cluster Tendency) in combination with 5-nearest neighbour model was the most robust signature. When applied to the explorative cohort, the prediction of good response corresponded to an average Area under the curve (AUC) value of 0.65 ± 0.02. When the model was tested on the external validation cohort, it ensured a similar accuracy, with a slightly lower predictive ability (AUC of 0.63). Conclusions Radiomics-based, data-mining from simulation CT scans was shown to be feasible and reproducible in two independent cohorts, yielding fair accuracy in the prediction of response to neoadjuvant chemo-radiation.

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.

IntroductionStereotactic 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 methodsPatients 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.ResultsA 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.ConclusionOnline 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.

Background and purpose: Hybrid magnetic resonance linear accelerator (MR-Linac) systems represent a novel technology for online adaptive radiotherapy. 3D secondary dose calculation (SDC) of online adapted plans is required to assure patient safety. Currently, no 3D-SDC solution is available for 1.5T MR-Linac systems. Therefore, the aim of this project was to develop and validate a method for online automatic 3D-SDC for adaptive MR-Linac treatments. Materials and methods: An accelerator head model was designed for an 1.5T MR-Linac system, neglecting the magnetic field. The use of this model for online 3D-SDC of MR-Linac plans was validated in a three-step process: (1) comparison to measured beam data, (2) investigation of performance and limitations in a planning phantom and (3) clinical validation using n = 100 patient plans from different tumor entities, comparing the developed 3D-SDC with experimental plan QA. Results: The developed model showed median gamma passing rates compared to MR-Linac base data of 84.7%, 100% and 99.1% for crossplane, inplane and depth-dose-profiles, respectively. Comparison of 3D-SDC and full dose calculation in a planning phantom revealed that with ⩾5 beams gamma passing rates >95% can be achieved for central target locations. With a median calculation time of 1:23 min, 3D-SDC of online adapted clinical MR-Linac plans demonstrated a median gamma passing rate of 98.9% compared to full dose calculation, whereas experimental plan QA reached 99.5%. Conclusion: Here, we describe the first technical 3D-SDC solution for online adaptive MR-guided radiotherapy. For clinical situations with peripheral targets and a small number of beams additional verification appears necessary. Further improvement may include 3D-SDC with consideration of the magnetic field.

Background and purpose: The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work. Methods: A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers. Results: The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work). Conclusion: COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting.

Purpose: Magnetic resonance imaging guided radiotherapy (MRgRT) allows treatment plan adaptation on the MRI of the day. For dose calculations, a structure-specific bulk relative electron density (RED) overwrite derived from a planning computed tomography (CT) poses as one possible treatment workflow. However, this approach introduces uncertainties due to assignment of mean densities and requires a planning CT. The aim of this study was to investigate the uncertainty of the used patient-specific (PSCT) dose calculation in contrast to the correct calculation on a CT and compare to MR-only workflows using population-based bulk ED (PBCT) and artificial intelligence–based pseudo-CTs (AICT).Methods: Twenty primary prostate cancer patients treated on the 1.5 T MR-Linac were chosen from the clinical database, based on best visual congruence between the planning CT and daily MRI. CT-based reference dose distribution was compared to different pseudo-CT approaches. 1) For PSCT, mean REDs for the femur, pelvis, sacrum, rectum, bladder, and patient were assigned based on individual mean CT densities. 2) Population-based mean REDs were derived based on 50 previous, independent patients and assigned to the structures for the PBCT approach. 3) An AI model for pseudo-CT generation was trained using end-to-end ensembled self-supervised GANs and used to create AICTs from T2w-MRIs. For comparison, the CT was registered to the MRI, structures rigidly propagated, and treatment plans recalculated. Differences of DVH parameters were analyzed, and dose distributions were compared using gamma analysis.Results: All approaches were able to reproduce the dose distribution accurately, according to a gamma criterion of 3%/3 mm, with pass rates greater than 98%. Applying a 2%/2 mm criterion, the median gamma pass rates for PSCT, PBCT, and AICT resulted in 98.6%, 98.2%, and 99.0%, respectively. The median differences for PTV D98% resulted in 0.13 Gy for AICT, −0.31 Gy for PBCT, and −0.32 Gy for PSCT. The OAR-related DVH parameter showed similar results between the three investigated methods.Conclusion: In this study, a detailed analysis of uncertainties of MR-only treatment planning concepts for pelvic MRgRT was performed. Both a PBCT and an AICT approach, which bypass the need for a planning CT, may be considered clinically acceptable while reducing imaging dose and registration issues.

Purpose: To compare treatment plans of two different rectal boost strategies: up-front versus adaptive boost at the 1.5 T MR-Linac. Methods: Patients with locally advanced rectal cancer (LARC) underwent standard neoadjuvant radiochemotherapy with 50.4 Gy in 28 fractions. T2-weighted MRI prior and after the treatment session were acquired to contour gross tumor volumes (GTVs) and organs at risk (OARs). The datasets were used to simulate four different boost strategies (all with 15 Gy/5 fractions in addition to 50.4 Gy): up-front boost (5 daily fractions in the first week of treatment) and an adaptive boost (one boost fraction per week). Both strategies were planned using standard and reduced PTV margins. Intra-fraction motion was assessed by pre- and post-treatment MRI-based contours. Results: Five patients were included and a total of 44 MRI sets were evaluated. The median PTV volumes of the adaptive boost were significantly smaller than for the up-front boost (81.4 cm3 vs 44.4 cm3 for PTV with standard margins; 31.2 cm3 vs 15 cm3 for PTV with reduced margins; p = 0.031). With reduced margins the rectum was significantly better spared with an adaptive boost rather than with an up-front boost: V60Gy and V65Gy were 41.2% and 24.8% compared with 59% and 29.9%, respectively (p = 0.031). Median GTV intra-fractional motion was 2 mm (range 0–8 mm). Conclusions: The data suggest that the adaptive boost strategy exploiting tumor-shrinkage and reduced margin might result in better sparing of rectum and anal canal. Individual margin assessment, motion management and real-time adaptive radiotherapy appear attractive applications of the 1.5 T MR-Linac for further testing of individualized and safe dose escalation in patients with rectal cancer.

Many preclinical and clinical observations support that functional magnetic resonance imaging (MRI), such as diffusion weighted (DW) and dynamic contrast enhanced (DCE) MRI, might have a predictive value for radiotherapy. The aim of this review was to assess the current status of quantitative MRI on hybrid MR-Linacs. In a literature research, four publications were identified, investigating technical feasibility, accuracy, repeatability and reproducibility of DW and DCE-MRI in phantoms and first patients. Accuracy and short term repeatability was

Correction factors for reference dosimetry in magnetic resonance (MR) imaging-guided radiation therapy (kB→,M,Q) are often determined in setups that combine a conventional 6 MV linac with an electromagnet. This study investigated whether results based on these measurements were applicable for a 7 MV MR-linac using Monte Carlo simulations. For a Farmer-type ionization chamber, kB→,M,Q was assessed for different tissue-phantom ratios (TPR20,10). kB→,M,Q differed by 0.0029(43) between TPR20,10=0.6790(23)(6 MV linac) and TPR20,10=0.7028(14) (7 MV MR-linac) at 1.5T. The agreement was best in an orientation in which the secondary electrons were deflected to the stem of the ionization chamber.

Background and purpose: Physical and mental well-being are crucial for oncology professionals as they affect performance at work. Personality traits, as alexithymia and empathy, may influence professional quality of life. Alexithymia involves diminished skills in emotion processing and awareness. Empathy is pertinent to the ability to understand another’s ‘state of mind/emotion’. The PROject on Burn-Out in RadiatioN Oncology (PRO BONO) investigates professional quality of life amongst radiation oncology professionals, exploring the role of alexithymia and empathy. The present study reports on data pertinent to radiation therapists (RTTs). Material and methods: An online survey targeted ESTRO members. Participants were asked to fill out 3 questionnaires for alexithymia, empathy and professional quality of life: (a) Toronto Alexithymia Scale (TAS-20); (b) Interpersonal Reactivity Index (IRI); (c) Professional Quality of Life Scale (ProQoL). The present analysis focuses on RTTS to evaluate compassion satisfaction (CS), secondary traumatic stress (STS) and Burnout and their correlation with alexithymia and empathy, using generalized linear modeling. Covariates found significant at univariate linear regression analysis were included in the multivariate linear regression model. Results: A total of 399 RTTs completed all questionnaires. The final model for the burnout scale of ProQoL found, as significal predictors, the TAS-20 total score (β = 0.46, p

The key goal and main challenge of radiation therapy is the elimination of tumors without any concurring damages of the surrounding healthy tissues and organs. Radiation doses required to achieve sufficient cancer‐cell kill exceed in most clinical situations the dose that can be tolerated by the healthy tissues, especially when large parts of the affected organ are irradiated. High‐precision radiation oncology aims at optimizing tumor coverage, while sparing normal tissues. Medical imaging during the preparation phase, as well as in the treatment room for localization of the tumor and directing the beam, referred to as image‐guided radiotherapy (IGRT), is the cornerstone of precision radiation oncology. Sophisticated high‐resolution real‐time IGRT using X‐rays, computer tomography, magnetic resonance imaging, or ultrasound, enables delivery of high radiation doses to tumors without significant damage of healthy organs. IGRT is the most convincing success story of radiation oncology over the last decades, and it remains a major driving force of innovation, contributing to the development of personalized oncology, for example, through the use of real‐time imaging biomarkers for individualized dose delivery.

Background and purpose: Hypoxia Positron-Emission-Tomography (PET) as well as Computed Tomography (CT) radiomics have been shown to be prognostic for radiotherapy outcome. Here, we investigate the stratification potential of CT-radiomics in head and neck cancer (HNC) patients and test if CT-radiomics is a surrogate predictor for hypoxia as identified by PET. Materials and methods: Two independent cohorts of HNC patients were used for model development and validation, HN1 (n = 149) and HN2 (n = 47). The training set HN1 consisted of native planning CT data whereas for the validation cohort HN2 also hypoxia PET/CT data was acquired using [18F]-Fluoromisonidazole (FMISO). Machine learning algorithms including feature engineering and classifier selection were trained for two-year loco-regional control (LRC) to create optimal CT-radiomics signatures.Secondly, a pre-defined [18F]FMISO-PET tumour-to-muscle-ratio (TMRpeak ≥ 1.6) was used for LRC prediction. Comparison between risk groups identified by CT-radiomics or [18F]FMISO-PET was performed using area-under–the-curve (AUC) and Kaplan-Meier analysis including log-rank test. Results: The best performing CT-radiomics signature included two features with nearest-neighbour classification (AUC = 0.76 ± 0.09), whereas AUC was 0.59 for external validation. In contrast, [18F]FMISO TMRpeak reached an AUC of 0.66 in HN2. Kaplan-Meier analysis of the independent validation cohort HN2 did not confirm the prognostic value of CT-radiomics (p = 0.18), whereas for [18F]FMISO-PET significant differences were observed (p = 0.02). Conclusions: No direct correlation of patient stratification using [18F]FMISO-PET or CT-radiomics was found in this study. Risk groups identified by CT-radiomics or hypoxia PET showed only poor overlap. Direct assessment of tumour hypoxia using PET seems to be more powerful to stratify HNC patients.

Background and purpose: The professional quality of life of radiation oncology professionals can be influenced by different contributing factors, including personality traits. Alexithymia involves deficits in emotion processing and awareness. Empathy is the ability to understand another’s ‘state of mind/emotion’. We investigated professional quality of life, including burnout, in radiation oncology, exploring the role of alexithymia and empathy and targeting the population of medical physicists (MPs), since this professional category is usually underrepresented in surveys exploring professional well-being in radiation oncology and MPs may experience professional distress given the increasing complexity of multimodal cancer care. Material and methods: An online survey was addressed to ESTRO members. Participants filled out three questionnaires to evaluate alexithymia, empathy and professional quality of life: a) Toronto Alexithymia Scale (TAS-20); b) Interpersonal Reactivity Index (IRI); c) Professional Quality of Life Scale (ProQoL). Professional quality of life as per ProQoL was considered as dependent variable. The three domains of the ProQoL, namely compassion satisfaction (CS), secondary traumatic stress (STS) and burnout were correlated with alexithymia (as per TAS-20) and empathy (as per IRI with three subcategories: empathic concern, perspective taking and personal distress) and demographic/professional characteristics as independent variables. Generalized linear modeling was used. Significant covariates on univariate linear regression analysis were included in the multivariate linear regression model. Results: A total of 308 medical physicists completed all questionnaires. Alexithymia as per TAS-20 was correlated to decreased CS (β = −0.25, p

Abstract Background As optic nerve sheath meningiomas (ONSM) are rare, there are no prospective studies. Our retrospective analysis focusses on a cohort of patients with uniform disease characteristics all treated with the same radiotherapy regimen. We describe treatment decision making, radiotherapy planning and detailed neuro-ophthalmological outcome of the patients. Methods 26 patients with unilateral ONSM extending only to the orbit and the optic canal were evaluated for neuro-ophthalmological outcome. Radiation treatment was planned in a simultaneous integrated boost approach to gross tumor volume (GTV) + 2 mm / 5 mm to 54 Gy / 51 Gy in 1.8 Gy / 1.7 Gy fractions. Follow-up was done by specialized neuro-ophthalmologists. Visual acuity and visual field defects were evaluated after therapy as well as during follow-up. Results Interdisciplinary treatment decision for patients with ONSM follows a rather complex decision tree. Radiation treatment planning (equivalent uniform dose (EUD), maximum dose to the optic nerve) improved with experience over time. With this patient selection visual acuity as well as visual field improved significantly at first follow-up after treatment. For visual acuity this also applied to patients with severe defects before treatment. Long term evaluation showed 16 patients with improved visual function, 6 were stable, in 4 patients visual function declined. Interdisciplinary case discussion rated the visual decline as radiation-associated in two patients. Conclusions With stringent patient selection radiotherapy for unilateral primary ONSM to 51 Gy / 54 Gy is safe and leads to significantly improved visual function. Interdisciplinary treatment decision and experience of the radiation oncology team play a major role.

PurposeDaily quantitative MR imaging during radiotherapy of cancer patients has become feasible with MRI systems integrated with linear accelerators (MR-linacs). Quantitative images could be used for treatment response monitoring. With intravoxel incoherent motion (IVIM) MRI, it is possible to acquire perfusion information without the use of contrast agents. In this multicenter study, daily IVIM measurements were performed in prostate cancer patients to identify changes that potentially reflect response to treatment.Materials and MethodsForty-three patients were included, treated with 20 fractions of 3 Gy on a 1.5 T MR-linac. IVIM measurements were performed on each treatment day. The diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were calculated based on the median signal intensities in the non-cancerous prostate and the tumor. Repeatability coefficients (RCs) were determined based on the first two treatment fractions. Separate linear mixed-effects models were constructed for the three IVIM parameters.ResultsIn total, 726 fractions were analyzed. Pre-treatment average values, measured on the first fraction before irradiation, were 1.46 × 10−3 mm2/s, 0.086, and 28.7 × 10−3 mm2/s in the non-cancerous prostate and 1.19 × 10−3 mm2/s, 0.088, and 28.9 × 10−3 mm2/s in the tumor, for D, f, and D*, respectively. The repeatability coefficients for D, f, and D* in the non-cancerous prostate were 0.09 × 10−3 mm2/s, 0.05, and 15.3 × 10−3 mm2/s. In the tumor, these values were 0.44 × 10−3 mm2/s, 0.16, and 76.4 × 10−3 mm2/s. The mixed effects analysis showed an increase in D of the tumors over the course of treatment, while remaining stable in the non-cancerous prostate. The f and D* increased in both the non-cancerous prostate and tumor.ConclusionsIt is feasible to perform daily IVIM measurements on an MR-linac system. Although the repeatability coefficients were high, changes in IVIM perfusion parameters were measured on a group level, indicating that IVIM has potential for measuring treatment response.

In the past few years, radiotherapy (RT) has experienced a major technological innovation with the development of hybrid machines combining magnetic resonance (MR) imaging and linear accelerators. This new technology for MR-guided cancer treatment has the potential to revolutionize the field of adaptive RT due to the opportunity to provide high-resolution, real-time MR imaging before and during treatment application. However, from a technical point of view, several challenges remain which need to be tackled to ensure safe and robust real-time adaptive MR-guided RT delivery. In this manuscript, several technical challenges to MR-guided RT are discussed. Starting with magnetic field strength tradeoffs, the potential and limitations for purely MR-based RT workflows are discussed. Furthermore, the current status of real-time 3D MR imaging and its potential for real-time RT are summarized. Finally, the potential of quantitative MR imaging for future biological RT adaptation is highlighted.

Purpose: To review the potential and challenges of integrating diffusion weighted magnetic resonance imaging (DWI) into radiotherapy (RT). Content: Details related to image acquisition of DWI for RT purposes are discussed, along with the challenges with respect to geometric accuracy and the robustness of quantitative parameter extraction. An overview of diffusion- and perfusion-related parameters derived from mono- and bi-exponential models is provided, and their role as potential RT biomarkers is discussed. Recent studies demonstrating potential of DWI in different tumor sites such as the head and neck, rectum, cervix, prostate, and brain, are reviewed in detail. Conclusion: DWI has shown promise for RT outcome prediction, response assessment, as well as for tumor delineation and characterization in several cancer types. Geometric and quantification robustness is challenging and has to be addressed adequately. Evaluation in larger clinical trials with well designed imaging protocol and advanced analysis models is needed to develop the optimal strategy for integrating DWI in RT.

An amendment to this paper has been published and can be accessed via the original article.

In order to compensate for the increased oxygen consumption in growing tumors, tumors need angiogenesis and vasculogenesis to increase the supply. Insufficiency in this process or in the microcirculation leads to hypoxic tumor areas with a significantly reduced pO2, which in turn leads to alterations in the biology of cancer cells as well as in the tumor microenvironment. Cancer cells develop more aggressive phenotypes, stem cell features and are more prone to metastasis formation and migration. In addition, intratumoral hypoxia confers therapy resistance, specifically radioresistance. Reactive oxygen species are crucial in fixing DNA breaks after ionizing radiation. Thus, hypoxic tumor cells show a two- to threefold increase in radioresistance. The microenvironment is enriched with chemokines (e.g., SDF-1) and growth factors (e.g., TGFβ) additionally reducing radiosensitivity. During recent years hypoxia has also been identified as a major factor for immune suppression in the tumor microenvironment. Hypoxic tumors show increased numbers of myeloid derived suppressor cells (MDSCs) as well as regulatory T cells (Tregs) and decreased infiltration and activation of cytotoxic T cells. The combination of radiotherapy with immune checkpoint inhibition is on the rise in the treatment of metastatic cancer patients, but is also tested in multiple curative treatment settings. There is a strong rationale for synergistic effects, such as increased T cell infiltration in irradiated tumors and mitigation of radiation-induced immunosuppressive mechanisms such as PD-L1 upregulation by immune checkpoint inhibition. Given the worse prognosis of patients with hypoxic tumors due to local therapy resistance but also increased rate of distant metastases and the strong immune suppression induced by hypoxia, we hypothesize that the subgroup of patients with hypoxic tumors might be of special interest for combining immune checkpoint inhibition with radiotherapy.