An essentially radiation-transparent body coil integrated with a patient rotation system for MR-guided particle therapy.

BACKGROUND: The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. PURPOSE: In MR-guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR-guided particle therapy was developed with minimal ion attenuation while maintaining flexibility in treatment. METHODS: A birdcage coil consisting of nearly radiation-transparent materials was designed and constructed for a closed-bore 1.5 T MR system. Additionally, the coil was mounted on a rotatable patient capsule for flexible positioning of the patient relative to the beam. The ion attenuation of the RF coil was investigated in theory and via measurements of the Bragg peak position. To characterize the imaging quality of the RF coil, transmit and receive field distributions were simulated and measured inside a homogeneous tissue-simulating phantom for various rotation angles of the patient capsule ranging from 0° to 345° in steps of 15°. Furthermore, simulations with a heterogeneous human voxel model were performed to better estimate the effect of real patient loading, and the RF coil was compared to the internal body coil in terms of SNR for a full rotation of the patient capsule. RESULTS: The RF coil (total water equivalent thickness (WET) ≈ 420 µm, WET of conductor ≈ 210 µm) can be considered to be radiation-transparent, and a measured transmit power efficiency (B1 +/ P $\sqrt {\mathrm{P}} $ ) between 0.17 µT/ W $\sqrt {\mathrm{W}} $ and 0.26 µT/ W $\sqrt {\mathrm{W}} $ could be achieved in a volume (Δz = 216 mm, complete x and y range) for the 24 investigated rotation angles of the patient capsule. Furthermore, homogeneous transmit and receive field distributions were measured and simulated in the transverse, coronal and sagittal planes in a homogeneous phantom and a human voxel model. In addition, the SNR of the radiation-transparent RF coil varied between 103 and 150, in the volume (Δz = 216 mm) of a homogeneous phantom and surpasses the SNR of the internal body coil for all rotation angles of the patient capsule. CONCLUSIONS: A radiation-transparent RF coil was developed and built that enables flexible patient to beam positioning via full rotation capability of the RF coil and patient relative to the beam, with results providing promising potential for adaptive MR-guided particle therapy.

Dosimetric benefit of online treatment plan adaptation in stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer.

Background: Apart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer. Materials and methods: 32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models. Results: In 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage ≥95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage ≥98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were <38.5 Gy in 93% vs. 100% before and after online adaptation. The constraint at the urethra with a dose of <37.5 Gy was achieved in 59% vs. 93% before and after online adaptation. Conclusion: Online adaptive plan adaptation improves target volume coverage and reduces doses to OAR in MR-guided SBRT of localized prostate cancer. Online plan adaptation could potentially further reduce acute and long-term side effects and improve local failure rates in MR-guided SBRT of localized prostate cancer.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer.

Background and purpose: Ultra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methods: Twenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5 × 7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p < 0.05). Results: Normalized to the baseline, the accumulated PTV* D95% increased significantly by 2.7 % ([1.5, 4.3]%) through adaptation, and the CTV* D98% by 1.2 % ([0.1, 1.7]%). For the OARs after adaptation, accumulated bladder D0.2cc decreased by 0.4 % ([-1.2, 0.4]%), urethra+2mmD0.2cc by 0.8 % ([-1.6, -0.1]%), while rectum D0.2cc increased by 2.6 % ([1.2, 4.9]%). For all patients, rectum D0.2cc was still below the clinical constraint. Results of both DIR approaches differed on average by less than 0.2 %. Conclusions: Online adaptation in MRgRT improved target coverage and OARs sparing at the level of accumulated dose.

Essential parameters needed for a U-Net-based segmentation of individual bones on planning CT images in the head and neck region using limited datasets for radiotherapy application.

Objective.The field of radiotherapy is highly marked by the lack of datasets even with the availability of public datasets. Our study uses a very limited dataset to provide insights on essential parameters needed to automatically and accurately segment individual bones on planning CT images of head and neck cancer patients.Approach.The study was conducted using 30 planning CT images of real patients acquired from 5 different cohorts. 15 cases from 4 cohorts were randomly selected as training and validation datasets while the remaining were used as test datasets. Four experimental sets were formulated to explore parameters such as background patch reduction, class-dependent augmentation and incorporation of a weight map on the loss function.Main results.Our best experimental scenario resulted in a mean Dice score of 0.93 ± 0.06 for other bones (skull, mandible, scapulae, clavicles, humeri and hyoid), 0.93 ± 0.02 for ribs and 0.88 ± 0.03 for vertebrae on 7 test cases from the same cohorts as the training datasets. We compared our proposed solution approach to a retrained nnU-Net and obtained comparable results for vertebral bones while outperforming in the correct identification of the left and right instances of ribs, scapulae, humeri and clavicles. Furthermore, we evaluated the generalization capability of our proposed model on a new cohort and the mean Dice score yielded 0.96 ± 0.10 for other bones, 0.95 ± 0.07 for ribs and 0.81 ± 0.19 for vertebrae on 8 test cases.Significance.With these insights, we are challenging the utilization of an automatic and accurate bone segmentation tool into the clinical routine of radiotherapy despite the limited training datasets.

Leaf-individual calibration for a double stack multileaf collimator in photon radiotherapy.

Background and Purpose: In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs. Materials and Methods: MLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan. Results: All positions in the motor step - position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2 ± 0.1 mm for X1 (left bank) and 0.2 ± 0.2 mm for X2 (right bank). The accuracy of the leaf position evaluation was 0.2 mm (95% confidence level). The MLC calibration remained stable over four months. Small MLC leaf position errors (e.g. 1.2 mm field size reduction) resulted in important dose errors (-5.8 %) for small quadratic fields of 0.83 × 0.83 cm2. Single stack position accuracy was essential for highly modulated treatment plans. Conclusions: LIMCA is a new double stack MLC calibration method that increases treatment accuracy from four angles and for all moving leaves.

Long-Term Clinical Results of MR-Guided Stereotactic Body Radiotherapy of Liver Metastases.

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rank p = 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging.

Quality assurance and temporal stability of a 1.5 T MRI scanner for MR-guided Photon and Particle Therapy.

PURPOSE: To describe performance measurements, adaptations and time stability over 20 months of a diagnostic MR scanner for integration into MR-guided photon and particle radiotherapy. MATERIAL AND METHODS: For realization of MR-guided photon and particle therapy (MRgRT/MRgPT), a 1.5 T MR scanner was installed at the Heidelberg Ion Beam Therapy Center. To integrate MRI into the treatment process, a flat tabletop and dedicated coil holders for flex coils were used, which prevent deformation of the patient external contour and allow for the use of immobilization tools for reproducible positioning. The signal-to-noise ratio (SNR) was compared for the diagnostic and therapy-specific setup using the flat couch top and flexible coils for the a) head & neck and b) abdominal region as well as for different bandwidths and clinical pulse sequences. Additionally, a quality assurance (QA) protocol with monthly measurements of the ACR phantom and measurement of geometric distortions for a large field-of-view (FOV) was implemented to assess the imaging quality parameters of the device over the course of 20 months. RESULTS: The SNR measurements showed a decreased SNR for the RT-specific as compared to the diagnostic setup of (a) 26% to 34% and (b) 11% to 33%. No significant bandwidth dependency for this ratio was found. The longitudinal assessment of the image quality parameters with the ACR and distortion phantom confirmed the long-term stability of the MRI device. CONCLUSION: A diagnostic MRI was commissioned for use in MR-guided particle therapy. Using a radiotherapy specific setup, a high geometric accuracy and signal homogeneity was obtained after some adaptions and the measured parameters were shown to be stable over a period of 20 months.

Comparison of different dose accumulation strategies to estimate organ doses after stereotactic magnetic resonance-guided adaptive radiotherapy.

INTRODUCTION: Re-irradiation is frequently performed in the era of precision oncology, but previous doses to organs-at-risk (OAR) must be assessed to avoid cumulative overdoses. Stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) enables highly precise ablation of tumors close to OAR. However, OAR doses may change considerably during adaptive treatment, which complicates potential re-irradiation. We aimed to compare the baseline plan with different dose accumulation techniques to inform re-irradiation. PATIENTS & METHODS: We analyzed 18 patients who received SMART to lung or liver tumors inside prospective databases. Cumulative doses were calculated inside the planning target volumes (PTV) and OAR for the adapted plans and theoretical non-adapted plans via (1) cumulative dose volume histograms (DVH sum plan) and (2) deformable image registration (DIR)-based dose accumulation to planning images (DIR sum plan). We compared cumulative dose parameters between the baseline plan, DVH sum plan and DIR sum plan using equivalent doses in 2 Gy fractions (EQD2). RESULTS: Individual patients presented relevant increases of near-maximum doses inside the proximal bronchial tree, spinal cord, heart and gastrointestinal OAR when comparing adaptive treatment to the baseline plans. The spinal cord near-maximum doses were significantly increased in the liver patients (D2% median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.4 Gy, p = 0.04; D0.1 cm³ median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.5 Gy, p = 0.04). Three OAR overdoses occurred during adaptive treatment (DIR sum: 1, DVH sum: 2), and four more intense OAR overdoses would have occurred during non-adaptive treatment (DIR sum: 4, DVH sum: 3). Adaptive treatment maintained similar PTV coverages to the baseline plans, while non-adaptive treatment yielded significantly worse PTV coverages in the lung (D95% median: baseline 86.4 Gy, DIR sum 82.4 Gy, DVH sum 82.2 Gy, p = 0.006) and liver patients (D95% median: baseline 87.4 Gy, DIR sum 82.1 Gy, DVH sum 81.1 Gy, p = 0.04). CONCLUSION: OAR doses can increase during SMART, so that re-irradiation should be planned based on dose accumulations of the adapted plans instead of the baseline plan. Cumulative dose volume histograms represent a simple and conservative dose accumulation strategy.

Stereotactic magnetic resonance-guided online adaptive radiotherapy of adrenal metastases combines high ablative doses with optimized sparing of organs at risk.

Purpose/Objective: To evaluate the potential of stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) to fulfill dose recommendations for stereotactic body radiotherapy (SBRT) of adrenal metastases and spare organs at risk (OAR). Materials and methods: In this subgroup analysis of a prospective registry trial, 22 patients with adrenal metastases were treated on a 0.35 T MR-Linac in 5-12 fractions with fraction doses of 4-10 Gy. Baseline plans were re-calculated to the anatomy of the day. These predicted plans were reoptimized to generate adapted plans. Baseline, predicted and adapted plans were compared with regard to PTV objectives, OAR constraints and published dose recommendations. Results: The cohort comprised patients with large GTV (median 36.0 cc) and PTV (median 66.6 cc) and predominantly left-sided metastases. 179 of 181 fractions (98.9 %) were adapted because of PTV and/or OAR violations. Predicted plans frequently violated PTV coverage (99.4 %) and adjacent OAR constraints (bowel: 32.9 %, stomach: 32.8 %, duodenum: 10.4 %, kidneys: 10.8 %). In the predicted plans, the volume exposed to the maximum dose was exceeded up to 16-fold in the duodenum and up to 96-fold in the spinal cord. Adapted plans significantly reduced OAR violations by 96.4 % for the bowel, 98.5 % for the stomach, 85.6 % for the duodenum and 83.3 % for the kidneys. Plan adaptation improved PTV coverage from 82.7 ± 8.1 % to 90.6 ± 4.9 % (p < 0.001). Furthermore, recently established target volume thresholds could easily be fulfilled with SMART. No toxicities > grade II occurred. Conclusion: SMART fulfills established GTV and PTV dose recommendations while simultaneously sparing organs at risk even in a challenging cohort.

To fly or not to fly: Stereotactic MR-guided adaptive radiotherapy effectively treats ultracentral lung tumors with favorable long-term outcomes.

BACKGROUND: Stereotactic radiotherapy of ultracentral lung tumors (ULT) is challenging as it may cause overdoses to sensitive mediastinal organs with severe complications. We aimed to describe long-term outcomes after stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) as an innovative treatment of ULT. PATIENTS & METHODS: We analyzed 36 patients that received SMART to 40 tumors between 02/2020 - 08/2021 inside prospective databases. ULT were defined by planning target volume (PTV) overlap with the proximal bronchial tree or esophagus. We calculated Kaplan Meier estimates for overall survival (OS) and progression-free survival (PFS), and competing risk estimates for the incidence of tumor progression and treatment-related toxicities. ULT patients (N = 16) were compared to non-ULT patients (N = 20). RESULTS: Baseline characteristics were similar between ULT and non-ULT, but ULT were larger (median PTV: ULT 54.7 cm3, non-ULT 19.2 cm3). Median follow-up was 23.6 months. ULT and non-ULT showed a similar OS (2-years: ULT 67%, non-ULT 60%, p = 0.7) and PFS (2-years: ULT 37%, non-ULT 34%, p = 0.73). Progressions occurred mainly at distant sites (2-year incidence of distant progression: ULT 63%, non-ULT 61%, p = 0.77), while local tumor control was favorable (2-year incidence of local progression: ULT 7%, non-ULT 0%, p = 0.22). Treatment of ULT led to significantly more toxicities ≥ grade (G) 2 (ULT: 9 (56%), non-ULT: 1 (5%), p = 0.002). Most toxicities were moderate (G2). Two ULT patients developed high-grade toxicities: 1) esophagitis G3 and bronchial bleeding G4 after VEGF treatment, 2) bronchial bleeding G3. Estimated incidence of high-grade toxicities was 19% (3-48%) in ULT, and no treatment-related death occurred. CONCLUSION: Our small series supports SMART as potentially effective treatment of ULT. SMART with careful fractionation could reduce severe complications, but treatment of ULT remains a high-risk procedure and needs careful benefit-risk-assessment.

A body mass index-based method for "MR-only" abdominal MR-guided adaptive radiotherapy.

PURPOSE: Dose calculation for MR-guided radiotherapy (MRgRT) at the 0.35 T MR-Linac is currently based on deformation of planning CTs (defCT) acquired for each patient. We present a simple and robust bulk density overwrite synthetic CT (sCT) method for abdominal treatments in order to streamline clinical workflows. METHOD: Fifty-six abdominal patient treatment plans were retrospectively evaluated. All patients had been treated at the MR-Linac using MR datasets for treatment planning and plan adaption and defCT for dose calculation. Bulk density CTs (4M-sCT) were generated from MR images with four material compartments (bone, lung, air, soft tissue). The relative electron densities (RED) for bone and lung were extracted from contoured CT structure average REDs. For soft tissue, a correlation between BMI and RED was evaluated. Dose was recalculated on 4M-sCT and compared to dose distributions on defCTs assessing dose differences in the PTV and organs at risk (OAR). RESULTS: Mean RED of bone was 1.17 ±â€¯0.02, mean RED of lung 0.17 ±â€¯0.05. The correlation between BMI and RED for soft tissue was statistically significant (p < 0.01). PTV dose differences between 4M-sCT and defCT were Dmean: -0.4 ±â€¯1.0%, D1%: -0.3 ±â€¯1.1% and D95%: -0.5 ±â€¯1.0%. OARs showed D2%: -0.3 ±â€¯1.9% and Dmean: -0.1 ±â€¯1.4% differences. Local 3D gamma index pass rates (2%/2mm) between dose calculated using 4M-sCT and defCT were 96.8 ±â€¯2.6% (range 89.9-99.6%). CONCLUSION: The presented method for sCT generation enables precise dose calculation for MR-only abdominal MRgRT.

Dosimetric Benefit of Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Liver Metastases.

(1) Background: To assess dosimetry benefits of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of liver metastases. (2) Methods: This is a subgroup analysis of an ongoing prospective registry including patients with liver metastases. Patients were treated at the MRIdian Linac between February 2020 and April 2022. The baseline plan was recalculated based on the updated anatomy of the day to generate the predicted plan. This predicted plan could then be re-optimized to create an adapted plan. (3) Results: Twenty-three patients received 30 SMART treatment series of in total 36 liver metastases. Most common primary tumors were colorectal- and pancreatic carcinoma (26.1% respectively). Most frequent fractionation scheme (46.6%) was 50 Gy in five fractions. The adapted plan was significantly superior compared to the predicted plan in regard to planning-target-volume (PTV) coverage, PTV overdosing, and organs-at-risk (OAR) dose constraints violations (91.5 vs. 38.0%, 6 vs. 19% and 0.6 vs. 10.0%; each p < 0.001). Plan adaptation significantly increased median BEDD95 by 3.2 Gy (p < 0.001). Mean total duration of SMART was 72.4 min. (4) Conclusions: SMART offers individualized ablative irradiation of liver metastases tailored to the daily anatomy with significant superior tumor coverage and improved sparing of OAR.

Magnetic resonance guided adaptive stereotactic body radiotherapy for lung tumors in ultracentral location: the MAGELLAN trial (ARO 2021-3).

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT). PATIENTS AND METHODS: MAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc. ) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED3/10: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED3/10: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts. DISCUSSION: The results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT. Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.

SMART ablation of lymphatic oligometastases in the pelvis and abdomen: Clinical and dosimetry outcomes.

PURPOSE: To demonstrate dosimetry benefits and report clinical outcomes of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of abdominopelvic lymphatic oligometastases. PATIENTS & METHODS: Prospective registry data of 26 patients with 31 oligoprogressive lymphatic metastases (1-2 lesions) who received SMART between April 2020 and April 2021 was analyzed. Prostate cancer was the most common histology (69%). Most patients (63%) had received previous abdominopelvic radiotherapy (RT). SMART was delivered in 3-7 fractions based on planning target volume (PTV) location and previous dose exposures. For SMART, the baseline plan was recalculated on daily 3D MR-imaging (predicted plan), and plan adaptation was mandatory in case of planning objective violations. RESULTS: Plan adaptation was mostly performed due to violation of planning objectives in the predicted plan (134/140 fractions, 96%) and significantly improved plan dosimetry: (1) PTV coverage was increased (predicted: median 89%, adapted: median 95%, p < 0.001), (2) organs-at-risk (OAR) overdoses were reduced (predicted: 27/140 (19%), adapted: 1/140 (1%), p < 0.001) and (3) PTV overdoses were reduced (predicted: 21/140 (15%), adapted: 1/140 (1%), p < 0.001). After a median follow-up of 9.8 months, one patient had in-field tumor progression and twelve patients had out-field tumor progression (at 6 months: progression-free survival: 63% [46-88%], local control rate: 97% [90-100%]). Treatment was tolerated well and no grade ≥3 toxicity was reported. CONCLUSION: SMART improves target volume coverage and yields superior OAR protection compared to non-adaptive radiotherapy, thus representing an innovative approach to challenging cases, such as repeated radiotherapy.

Quality assurance for on-table adaptive magnetic resonance guided radiation therapy: A software tool to complement secondary dose calculation and failure modes discovered in clinical routine.

Online adaption of treatment plans on a magnetic resonance (MR)-Linac enables the daily creation of new (adapted) treatment plans using current anatomical information of the patient as seen on MR images. Plan quality assurance (QA) relies on a secondary dose calculation (SDC) that is required because a pretreatment measurement is impossible during the adaptive workflow. However, failure mode and effect analysis of the adaptive planning process shows a large number of error sources, and not all of them are covered by SDC. As the complex multidisciplinary adaption process takes place under time pressure, additional software solutions for pretreatment per-fraction QA need to be used. It is essential to double-check SDC input to ensure a safe treatment delivery. Here, we present an automated treatment plan check tool for adaptive radiotherapy (APART) at a 0.35 T MR-Linac. It is designed to complement the manufacturer-provided adaptive QA tool comprising SDC. Checks performed by APART include contour analysis, electron density map examinations, and fluence modulation complexity controls. For nine of 362 adapted fractions (2.5%), irregularities regarding missing slices in target volumes and organs at risks as well as in margin expansion of target volumes have been found. This demonstrates that mistakes occur and can be detected by additional QA measures, especially contour analysis. Therefore, it is recommended to implement further QA tools additional to what the manufacturer provides to facilitate an informed decision about the quality of the treatment plan.

Stereotactic body radiotherapy of lymph node metastases under MR-guidance: First clinical results and patient-reported outcomes.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is a noninvasive treatment option for lymph node metastases (LNM). Magnetic resonance (MR)-guidance offers superior tissue contrast and enables treatment of targets in close vicinity to radiosensitive organs at risk (OAR). However, literature on MR-guided SBRT of LNM is scarce with no report on outcome parameters. MATERIALS AND METHODS: We report a subgroup analysis of a prospective observational study comprising patients with LNM. Patients received MR-guided SBRT at our MRIdian Linac (ViewRay Inc., Mountain View, CA, USA) between January 2019 and February 2020. Local control (LC), progression-free survival (PFS) and overall survival (OS) analysis were performed using the Kaplan-Meier method with log rank test to test for significance (p < 0.05). Our patient-reported outcome questionnaire was utilized to evaluate patients' perspective. The CTCAE (Common Terminology Criteria for Adverse Events) v. 5.0 was used to describe toxicity. RESULTS: Twenty-nine patients (72.4% with prostate cancer; 51.7% with no distant metastases) received MR-guided SBRT for in total 39 LNM. Median dose was 27 Gy in three fractions, prescribed to the 80% isodose. At 1­year, estimated LC, PFS and OS were 92.6, 67.4 and 100.0%. Compared to baseline, six patients (20.7%) developed new grade I toxicities (mainly fatigue). One grade II toxicity occurred (fatigue), with no adverse event grade ≥III. Overall treatment experience was rated particularly positive, while the technically required low room temperature still represents the greatest obstacle in the pursuit of the ideal patient acceptance. CONCLUSION: MR-guided SBRT of LNM was demonstrated to be a well-accepted treatment modality with excellent preliminary results. Future studies should evaluate the clinical superiority to conventional SBRT.

Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Liver Tumors: Initial Clinical Experience and Patient-Reported Outcomes.

PURPOSE/OBJECTIVE: Stereotactic body radiation therapy (SBRT) has emerged as a valid treatment alternative for non-resectable liver metastases or hepatocellular carcinomas (HCC). Magnetic resonance (MR) guided SBRT has a high potential of further improving treatment quality, allowing for higher, tumoricidal irradiation doses whilst simultaneously sparing organs at risk. However, data on treatment outcome and patient acceptance is still limited. MATERIAL/METHODS: We performed a subgroup analysis of an ongoing prospective observational study comprising patients with liver metastases or HCC. Patients were treated with ablative MR-guided SBRT at the MRIdian Linac in the Department of Radiation Oncology at Heidelberg University Hospital between January 2019 and February 2020. Local control (LC) and overall survival (OS) analysis was performed using the Kaplan-Meier method. An in-house designed patient-reported outcome questionnaire was used to measure patients' experience with the MR-Linac treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). RESULTS: Twenty patients (with n = 18 metastases; n = 2 HCC) received MR-guided SBRT for in total 26 malignant liver lesions. Median biologically effective dose (BED at α/ß = 10) was 105.0 Gy (range: 67.2-112.5 Gy) and median planning target volume was 57.20 ml (range: 17.4-445.0 ml). Median treatment time was 39.0 min (range: 26.0-67.0 min). At 1-year, LC was 88.1% and OS was 84.0%. Grade I° gastrointestinal toxicity °occurred in 30.0% and grade II° in 5.0% of the patients with no grade III° or higher toxicity. Overall treatment experience was rated positively, with items scoring MR-Linac staff's performance and items concerning the breath hold process being among the top positively rated elements. Worst scored items were treatment duration, positioning and low temperature. CONCLUSION: MR-guided SBRT of liver tumors is a well-tolerated and well-accepted treatment modality. Initial results are promising with excellent local control and only mildest toxicity. However, prospective studies are warranted to truly assess the potential of MR-guided liver SBRT and to identify which patients profit most from this new versatile technology.

Artificial Intelligence in magnetic Resonance guided Radiotherapy: Medical and physical considerations on state of art and future perspectives.

Over the last years, technological innovation in Radiotherapy (RT) led to the introduction of Magnetic Resonance-guided RT (MRgRT) systems. Due to the higher soft tissue contrast compared to on-board CT-based systems, MRgRT is expected to significantly improve the treatment in many situations. MRgRT systems may extend the management of inter- and intra-fraction anatomical changes, offering the possibility of online adaptation of the dose distribution according to daily patient anatomy and to directly monitor tumor motion during treatment delivery by means of a continuous cine MR acquisition. Online adaptive treatments require a multidisciplinary and well-trained team, able to perform a series of operations in a safe, precise and fast manner while the patient is waiting on the treatment couch. Artificial Intelligence (AI) is expected to rapidly contribute to MRgRT, primarily by safely and efficiently automatising the various manual operations characterizing online adaptive treatments. Furthermore, AI is finding relevant applications in MRgRT in the fields of image segmentation, synthetic CT reconstruction, automatic (on-line) planning and the development of predictive models based on daily MRI. This review provides a comprehensive overview of the current AI integration in MRgRT from a medical physicist's perspective. Medical physicists are expected to be major actors in solving new tasks and in taking new responsibilities: their traditional role of guardians of the new technology implementation will change with increasing emphasis on the managing of AI tools, processes and advanced systems for imaging and data analysis, gradually replacing many repetitive manual tasks.

A practical implementation of risk management for the clinical introduction of online adaptive Magnetic Resonance-guided radiotherapy.

BACKGROUND AND PURPOSE: The clinical introduction of on-table adaptive radiotherapy with Magnetic Resonance (MR)-guided linear accelerators (Linacs) yields new challenges and potential risks. Since the adapted plan is created within a highly interdisciplinary workflow with the patient in treatment position, time pressure or erroneous communication may lead to various possibly hazardous situations. To identify risks and implement a safe workflow, a proactive risk analysis has been conducted. MATERIALS AND METHODS: A process failure mode, effects and criticality analysis (P-FMECA) was performed within a group of radiation therapy technologists, physicians and physicists together with an external moderator. The workflow for on-table adaptive MR-guided treatments was defined and for each step potentially hazardous situations were identified. The risks were evaluated within the team in order to homogenize risk assessment. The team elaborated and discussed possible mitigation strategies and carried out their implementation. RESULTS: In total, 89 risks were identified for the entire MR-guided online adaptive workflow. After mitigation, all risks could be minimized to an acceptable level. Overall, the need for a standardized workflow, clear-defined protocols together with the need for checklists to ensure protocol adherence were identified among the most important mitigation measures. Moreover, additional quality assurance processes and automated plan checks were developed. CONCLUSIONS: Despite additional workload and beyond the fulfilment of legal requirements, execution of the P-FMECA within an interdisciplinary team helped all involved occupational groups to develop and foster an open culture of safety and to ensure a consensus for an efficient and safe online adaptive radiotherapy workflow.

MR-guided radiotherapy of moving targets.

INTRODUCTION: Hybrid magnetic resonance (MR) linear accelerators (MR-Linacs) for radiotherapy allow for the visualization and tracking of moving target volumes during the entire treatment. This makes gated treatments possible, decreasing the irradiated volumes and thus sparing healthy tissue from unnecessary radiation dose. Conventionally, tumors that are subject to respiration motion are treated by irradiating the entire area of potential target presence (internal target volume, ITV). This study presents three patient cases (lung, adrenal gland, and liver tumors) treated with gated MR-guided radiotherapy and compares the treatment plans retrospectively with conventional ITV plans. MATERIALS AND METHODS: The gross tumor volume was delineated on MR and computed tomography (CT) images of the patients, and MR-Linac treatment plans were generated using additional clinical and planning target volume margins. The motion of the gross tumor volume was evaluated on two-dimensional cine-MRI images during the entire MR-Linac treatment. Based on the motion analysis, standard ITV-based plans were retrospectively created and compared by means of irradiated target volumes and dose-volume parameters. RESULTS: For the MR-Linac plans, the irradiated treatment volumes were reduced by an average of 62% across the three cases, and for one case the ITV-based target volume would have overlapped with a critical organ. Target volume coverage was much better and the lung and adrenal MR-Linac plans revealed superior sparing of the organs at risks thanks to gated treatments. CONCLUSION: Dosimetrically beneficial treatment plans with promising clinical outcomes can be applied when using gated MR-guided radiotherapy. Future studies will reveal which patients will benefit most from this technique. To utilize the full potential of online adaptive, individualized MR-guided therapy, the close collaboration of radio-oncology and radiology is needed.