Experimental characterization of four ionization chamber types in magnetic fields including intra-type variation.

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.

Full daily re-optimization improves plan quality during online adaptive radiotherapy.

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.

Reproducibility of diffusion-weighted magnetic resonance imaging in head and neck cancer assessed on a 1.5 T MR-Linac and comparison to parallel measurements on a 3 T diagnostic scanner.

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 mm2/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.

Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).

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.

MRI-Guided Adaptive Radiation Therapy.

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.

Impact of MRI on target volume definition in head and neck cancer patients.

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.

Longitudinal monitoring of Apparent Diffusion Coefficient (ADC) in patients with prostate cancer undergoing MR-guided radiotherapy on an MR-Linac at 1.5 T: a prospective feasibility study.

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 (MRI3T) 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 mm2/s vs. mean MRL-ADC during radiotherapy 1.38 ± 0.3 × 10-3 mm2/s, yielding a mean lesion ADC elevation of 0.41 ± 0.20 × 10-3 mm2/s, p < 0.001). Mean MRI3T-ADC at baseline was 0.78 ± 0.165 × 10-3 mm2/s vs. mean MRI3T-ADC during radiotherapy 0.99 ± 0.175 × 10-3 mm2/s, yielding a mean lesion ADC elevation of 0.21 ± 0.96 × 10-3 mm2/s p < 0.001). The absolute ADC values from MRL were consistently significantly higher than those from MRI3T at baseline and during radiotherapy (p < = 0.001). However, there was a strong positive correlation between MRL-ADC and MRI3T-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.

Automatic AI-based contouring of prostate MRI for online adaptive radiotherapy.

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.

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

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 .

Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models.

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 (SUVmean/peak/max) and tumor-to-muscle-ratios (TMRpeak/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 ADCvalley showed significant correlation to radiation resistance ([Formula: see text]). After 2 weeks of RT, FMISO_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.

Prospective evaluation of in vivo and phantom repeatability and reproducibility of diffusion-weighted MRI sequences on 1.5 T MRI-linear accelerator (MR-Linac) and MR simulator devices for head and neck cancers.

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 EPIMR-linac, SPLICE, TSE, EPIMR sim, BLADE, RESOLVE. Repeatability/reproducibility wCV for EPIMR-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 mm2/s for most vials (EPIMR-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 EPIMR-linac, SPLICE, TSE, EPIMR 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.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

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.

Impact of endorectal filling on interobserver variability of MRI based rectal primary tumor delineation.

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 < 0.005 for approach 1 and 0.76 vs 0.64, p < 0.0001 for approach 2) and 95 %HD (6.9 mm vs 4.2 mm for approach 1, p = 0.04 and 8.9 mm vs 6.1 mm, p = 0.04 for approach 2). Delineated median tumor volumes and inter-quartile ranges were 26.99 cc [18.01-50.34 cc] in MRI_e and 44.20 [19.72-61.59 cc] in MRI_f scans respectively, p = 0.012. Conclusions: Although limited by the small number of patients, in this study the application of rectal ultrasound gel resulted in higher interobserver agreement in rectal GTV delineation. The endorectal gel filling might be a useful tool for future dose escalation strategies.

Clinical use of positron emission tomography for radiotherapy planning - Medical physics considerations.

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.

Soy lecithin: A beneficial substance for adjusting the ADC in aqueous solutions to the values of biological tissues.

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/mm2 ) were applied for ADC measurements. Quantitative relaxometry and MRS were performed for assessment of T1 , T2 , 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/mm2 ). ADC values ranged from 2.02 × 10-3  mm2 /s to 0.48 × 10-3  mm2 /s and cover the entire physiological range reported on biological tissue. Measured T1 /T2 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 T2 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 T2 values (by adding agar) almost independently of each other.

Online MR guided dose escalated radiotherapy for organ preservation in distal rectal cancer.

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.

Potential of Deep Learning in Quantitative Magnetic Resonance Imaging for Personalized Radiotherapy.

Quantitative magnetic resonance imaging (qMRI) has been shown to provide many potential advantages for personalized adaptive radiotherapy (RT). Deep learning models have proven to increase efficiency, robustness and speed for different qMRI tasks. Therefore, this article discusses the current state-of-the-art and potential future opportunities as well as challenges related to the use of deep learning in qMRI for target contouring, quantitative parameter estimation and also the generation of synthetic computerized tomography (CT) data based on MRI in personalized RT.

First Experience and Prospective Evaluation on Feasibility and Acute Toxicity of Online Adaptive Radiotherapy of the Prostate Bed as Salvage Treatment in Patients with Biochemically Recurrent Prostate Cancer on a 1.5T MR-Linac.

INTRODUCTION: Novel MRI-linear accelerator hybrids (MR-Linacs, MRL) promise an optimization of radiotherapy (RT) through daily MRI imaging with enhanced soft tissue contrast and plan adaptation on the anatomy of the day. These features might potentially improve salvage RT of prostate cancer (SRT), where the clinical target volume is confined by the mobile organs at risk (OAR) rectum and bladder. So far, no data exist about the feasibility of the MRL technology for SRT. In this study, we prospectively examined patients treated with SRT on a 1.5 T MRL and report on workflow, feasibility and acute toxicity. PATIENTS AND METHODS: Sixteen patients were prospectively enrolled within the MRL-01 study (NCT: NCT04172753). All patients were staged and had an indication for SRT after radical prostatectomy according to national guidelines. RT consisted of 66 Gy in 33 fractions or 66.5/70 Gy in 35 fractions in case of a defined high-risk region. On the 1.5 T MRL, daily plan adaption was performed using one of two workflows: adapt to shape (ATS, using contour adaptation and replanning) or adapt to position (ATP, rigid replanning onto the online anatomy with virtual couch shift). Duration of treatment steps, choice of workflow and treatment failure were recorded for each fraction of each patient. Patient-reported questionnaires about patient comfort were evaluated as well as extensive reporting of acute toxicity (patient reported and clinician scored). RESULTS: A total of 524/554 (94.6%) of fractions were successfully treated on the MRL. No patient-sided treatment failures occurred. In total, ATP was chosen in 45.7% and ATS in 54.3% of fractions. In eight cases, ATP was performed on top of the initial ATS workflow. Mean (range) duration of all fractions (on-table time until end of treatment) was 25.1 (17.6-44.8) minutes. Mean duration of the ATP workflow was 20.60 (17.6-25.2) minutes and of the ATS workflow 31.3 (28.2-34.1) minutes. Patient-reported treatment experience questionnaires revealed high rates of tolerability of the treatment procedure. Acute toxicity (RTOG, CTC as well as patient-reported CTC, IPSS and ICIQ) during RT and 3 months after was mild to moderate with a tendency of recovery to baseline levels at 3 months post RT. No G3+ toxicity was scored for any item. CONCLUSIONS: In this first report on SRT of prostate cancer patients on a 1.5 T MRL, we could demonstrate the feasibility of both available workflows. Daily MR-guided adaptive SRT of mean 25.1 min per fraction was well tolerated in this pretreated collective, and we report low rates of acute toxicity for this treatment. This study suggests that SRT on a 1.5 T MRL can be performed in clinical routine and it serves as a benchmark for future analyses.