Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Simultaneous implementation of unrelated tumour sites on the MR Linac: A review of the commissioning process from a radiographer perspective and lessons learned.

INTRODUCTION: This work reports on a systematic approach to select MRI sequences, quantify inter-observer image registration variation and determine patient positioning for the clinical implementation of MR-guided adaptive radiotherapy (MRgRT) in patients with oropharyngeal (H&N) and lung cancer. METHODS: A total of 30 participants (N=10 H&N and N=10 lung cancer patients and N=10 healthy participants) were scanned on the Elekta Unity Magnetic Resonance Linear Accelerator (MRL). Participant experience questionnaires were used to determine the most appropriate positioning device for lung treatments and tolerability of H&N immobilization devices within the confined MR Linac environment. Visual guided assessments (VGAs) completed by three observers (one oncologist and two radiographers) were used to determine the most suitable tissue weighting (using vendor-provided 3D T1w and T2w sequences) for online image registration. Offline MRI to CT and MRI to MRI rigid registrations were undertaken by nine radiographers using bony and soft tissue matching. Single-factor ANOVA and paired t-tests were utilized to determine the interobserver variation. RESULTS: Based on oncologist and patient feedback, lung cancer patients would be treated in a vac-bag with their arms by their sides, while H&N cancer patients would be immobilized using a 5-point fixation device and 5-point personalized thermoplastic shell. There was no clear preference for T1w or T2w images in the H&N cohort. However, observers preferred T2w sequences for tumour and organ at risk (OAR) visualization in the lung images. When a bony match was conducted, single-factor ANOVA tests showed no statistically significant differences between all H&N image registration types (p=0.09). For the soft-tissue registrations, T1w-CT and T1w-T1w registrations showed a statistically significant (p=0.01) reduction in inter-observer variability over T2w-CT registrations. Paired t-tests showed no statistically significant differences for bony or soft tissue matches using T1w or T2w sequences to the planning CT in the lung cohorts (p=0.63 and p=0.52, respectively). CONCLUSION: We describe the systematic approach to the selection of strategies for imaging, immobilization, and online image registration we used for H&N and lung cancer treatments on the MRL. This has facilitated the selection of the most appropriate adaptive MRgRT strategies for treating these sites at our institution.

Accelerated Hypofractionated Magnetic Resonance Guided Adaptive Radiation Therapy for Ultracentral Lung Tumors.

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-changer for tumors in these challenging locations, in close proximity to central organs at risk, such as the trachea, proximal bronchial tree, and esophagus. In this series, 13 consecutive patients, predominantly male (n = 9), with a median age of 71 (range (R): 46-85), underwent 195 MRgART fractions (all 60 Gy in 15 fractions) to metastatic (n = 12) or primary ultra-central lung tumors (n = 1). The median gross tumor volumes (GTVs) and planning target volumes (PTVs) were 20.72 cc (R: 0.54-121.65 cc) and 61.53 cc (R: 3.87-211.81 cc), respectively. The median beam-on time per fraction was 14 min. Adapted treatment plans were generated for all fractions, and indications included GTV/PTV undercoverage, OARs exceeding tolerance doses, or both indications in 46%, 18%, and 36% of fractions, respectively. Eight patients received concurrent systemic therapies, including immunotherapy (four), chemotherapy (two), and targeted therapy (two). The crude in-field loco-regional control rate was 92.3%. No CTCAE grade 3+ toxicities were observed. Our results offer promising insights, suggesting that MRgART has the potential to mitigate toxicities, enhance treatment precision, and improve overall patient care in the context of ultracentral lung tumors.

Impact of a contouring atlas on radiographer inter-observer variation in male pelvis radiotherapy.

PURPOSE/OBJECTIVE: To determine the impact of a MR-based contouring atlas for male pelvis radiotherapy delineation on inter-observer variation to support radiographer led real-time magnetic resonance image guided adaptive radiotherapy (MRgART). MATERIAL/METHODS: Eight RTTs contoured 25 MR images in the Monaco treatment planning system (Monaco 5.40.01), from 5 patients. The prostate, seminal vesicles, bladder, and rectum were delineated before and after the introduction of an atlas developed through multi-disciplinary consensus. Inter-observer contour variations (volume), time to contour and observer contouring confidence were determined at both time-points using a 5-point Likert scale. Descriptive statistics were used to analyse both continuous and categorical variables. Dice similarity coefficient (DSC), Dice-Jaccard coefficient (DJC) and Hausdorff distance were used to calculate similarity between observers. RESULTS: Although variation in volume definition decreased for all structures among all observers post intervention, the change was not statistically significant. DSC and DJC measurements remained consistent following the introduction of the atlas for all observers. The highest similarity was found in the bladder and prostate whilst the lowest was the seminal vesicles. The mean contouring time for all observers was reduced by 50% following the introduction of the atlas (53 to 27 minutes, p=0.01). For all structures across all observers, the mean contouring confidence increased significantly from 2.3 to 3.5 out of 5 (p=0.02). CONCLUSION: Although no significant improvements were observed in contour variation amongst observers, the introduction of the consensus-based contouring atlas improved contouring confidence and speed; key factors for a real-time RTT-led MRgART.

Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial.

BACKGROUND: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Dosimetric feasibility of direct post-operative MR-Linac-based stereotactic radiosurgery for resection cavities of brain metastases.

BACKGROUND: Post-operative radiosurgery (SRS) of brain metastases patients is typically planned on a post-recovery MRI, 2-4 weeks after resection. However, the intracranial metastasis may (re-)grow in this period. Planning SRS directly on the post-operative MRI enables shortening this time interval, anticipating the start of adjuvant systemic therapy, and so decreasing the chance of extracranial progression. The MRI-Linac (MRL) allows the simultaneous execution of the post-operative MRI and SRS treatment. The aim of this work was investigating the dosimetric feasibility of MRL-based post-operative SRS. METHODS: MRL treatments based on the direct post-operative MRI were simulated, including thirteen patients with resectable single brain metastases. The gross tumor volume (GTV) was contoured on the direct post-operative scans and compared to the post-recovery MRI GTV. Three plans for each patient were created: a non-coplanar VMAT CT-Linac plan (ncVMAT) and a coplanar IMRT MRL plan (cIMRT) on the direct post-operative MRI, and a ncVMAT plan on the post-recovery MRI as the current clinical standard. RESULTS: Between the direct post-operative and post-recovery MRI, 15.5 % of the cavities shrunk by > 2 cc, and 46 % expanded by ≥ 2 cc. Although the direct post-operative cIMRT plans had a higher median gradient index (3.6 vs 2.7) and median V3Gy of the skin (18.4 vs 1.1 cc) compared to ncVMAT plans, they were clinically acceptable. CONCLUSION: Direct post-operative MRL-based SRS for resection cavities of brain metastases is dosimetrically acceptable, with the advantages of increased patient comfort and logistics. Clinical benefit of this workflow should be investigated given the dosimetric plausibility.

Feasibility of delta radiomics-based pCR prediction for rectal cancer patients treated with magnetic resonance-guided adaptive radiotherapy.

Magnetic resonance-guided adaptive radiotherapy (MRgART) represents the latest frontier in precision radiotherapy. It is distinguished from other modalities by the possibility of acquiring high-contrast soft tissue images, combined with the ability to recalculate and re-optimize the plan on the daily anatomy. The extensive database of available images offers ample scope for using disciplines such as radiomics to try to correlate features and outcomes. This study aimed to correlate the change of radiomics feature along the treatment to pathological complete response (pCR) for locally advanced rectal cancer (LARC) patients. Twenty-eight LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT) with a short course (25 Gy, 5 Gy × 5f) MRgART at 1.5 Tesla MR-Linac were enrolled. The T2-weighted images acquired at each fraction, corresponding target delineation, pCR result of the surgical specimen, and clinical variables were collected. Seven families of features [First Order, Shape, Gray-level Co-occurrence Matrix (GLCM), Gray-level Dependence Matrix (GLDM), Gray-level Run Length Matrix (GLRLM), Gray-level Size Zone Matrix (GLSZM), and Neighborhood Gray Tone Difference Matrix (NGTDM)] were extracted, and delta features were calculated from the ratio of features of each successive fraction to those of the first fraction. Mann-Whitney U test and LASSO were utilized to reduce the dimension of features and select those features that are most significant to pCR. At last, the radiomics signatures were established by linear regression with the final set of features and their coefficients. A total of 581 radiomics features were extracted, and 2,324 delta features were calculated for each patient. Nineteen features and delta features, and one clinical variable (cN) were significant (p< 0.05) to pCR; seven predictive features were further selected and included in the linear regression to construct the radiomics signature significantly discriminating pCR and non-pCR groups (p< 0.05). Delta features based on MRI images acquired during a short course MRgART could potentially be used to predict treatment response in LARC patients undergoing nCRT.

A new workflow of the on-line 1.5-T MR-guided adaptive radiation therapy.

PURPOSE: The aim of this study was to develop a new workflow for 1.5-T magnetic resonance (MR)-guided on-line adaptive radiation therapy (MRgART) and assess its feasibility in achieving dose constraints. MATERIALS AND METHODS: We retrospectively evaluated the clinical data of patients who underwent on-line adaptive radiation therapy using a 1.5-T MR linear accelerator (MR-Linac). The workflow in MRgART was established by reviewing the disease site, number of fractions, and re-planning procedures. Five cases of prostate cancer were selected to evaluate the feasibility of the new workflow with respect to achieving dose constraints. RESULTS: Between December 2021 and September 2022, 50 consecutive patients underwent MRgART using a 1.5-T MR-Linac. Of these, 20 had prostate cancer, 10 had hepatocellular carcinoma, 6 had pancreatic cancer, 5 had lymph node oligo-metastasis, 3 had renal cancer, 3 had bone metastasis, 2 had liver metastasis from colon cancer, and 1 had a mediastinal tumor. Among a total of 247 fractions, 235 (95%) were adapt-to-shape (ATS)-based re-planning. The median ATS re-planning time in all 50 cases was 17 min. In the feasibility study, all dose constraint sets were met in all 5 patients by ATS re-planning. Conversely, a total of 14 dose constraints in 5 patients could not be achieved by virtual plan without using adaptive re-planning. These dose constraints included the minimum dose received by the highest irradiated volume of 1 cc in the planning target volume and the maximum dose of the rectal/bladder wall. CONCLUSION: A new workflow of 1.5-T MRgART was established and found to be feasible. Our evaluation of the dose constraint achievement demonstrated the effectiveness of the workflow.

Clinical Implementational and Site-Specific Workflows for a 1.5T MR-Linac.

MR-guided adaptive radiotherapy (MRgART) provides opportunities to benefit patients through enhanced use of advanced imaging during treatment for many patients with various cancer treatment sites. This novel technology presents many new challenges which vary based on anatomic treatment location, technique, and potential changes of both tumor and normal tissue during treatment. When introducing new treatment sites, considerations regarding appropriate patient selection, treatment planning, immobilization, and plan-adaption criteria must be thoroughly explored to ensure adequate treatments are performed. This paper presents an institution's experience in developing a MRgART program for a 1.5T MR-linac for the first 234 patients. The paper suggests practical treatment workflows and considerations for treating with MRgART at different anatomical sites, including imaging guidelines, patient immobilization, adaptive workflows, and utilization of bolus.

The impact of gadolinium-based MR contrast on radiotherapy planning for oropharyngeal treatment on the MR Linac.

PURPOSE: Gadolinium-based contrast agents (GBCAs) may add value to magnetic resonance (MR)-only radiotherapy (RT) workflows including on hybrid machines such as the MR Linac. The impact of GBCAs on RT dose distributions however have not been well studied. This work used retrospective GBCA-enhanced datasets to assess the dosimetric effect of GBCAs on head and neck plans. METHODS: Ten patients with oropharyngeal squamous cell carcinoma receiving RT from November 2018 to April 2020 were included in this study. RT planning included contrast-enhanced computed tomography (CT) and MR scans. A contrast agent "contour" was defined by delineating GBCA-enhanced regions using an agreed window/level threshold, transferred to the planning CT and given a standardized electron density (ED) of 1.149 in the Monaco treatment planning system (Elekta AB). Four plans were per patient calculated and compared using two methods: (1) optimized without contrast (Plan A) then recalculated with ED (Plan B), and (2) optimized with contrast ED (Plan C) then without (Plan D). For target parameters minimum and maximum doses to 1cc of PTVs, D95 values, and percent dose differences were calculated. Dose differences for organs-at-risk (OARs) were calculated as a percentage of the clinical tolerance value. For the purposes of this study, ±2% over the whole treatment course was considered to be a clinically acceptable dose deviation. Wilcoxon-signed rank tests were used to determine any dose differences within and between the two methods of optimization and recalculation (p < 0.05). Pearson's correlations were used to establish the relationship between gadolinium uptake volume in a structure (i.e., proportion of structure covered by a density override) and the resulting dose difference. RESULTS: The median percent dose differences for key reportable dosimetric parameters between non-contrast and simulated contrast plans were <1.2% over all fractions over all patients for reportable target parameters (mean 0.34%, range 0.22%-1.02%). The percent dose differences for maximum dose to 1cc of both PTV1 and PTV2 were significantly different after application of density override (p < 0.05) but only in method 2 (Plan C vs. Plan D). For D95 PTV1, there was a statistically significant effect of density override (p < 0.01), however only in method 1 (Plan A vs. Plan B). There were no significant differences between calculation methods of the impact of contrast in most target parameters with the exception of D95 PTV1 (p < 0.01) and for D95 PTV2 (p < 0.05). The median percent dose differences for reportable OAR parameters as a percentage of clinical planning tolerances were <2.0% over a full treatment course (mean 0.65%, range 0.27%-1.62%). There were no significant differences in dose to OARs within or between methods for contrast impact assessment. CONCLUSIONS: Dose differences to targets and OARs in oropharyngeal cancer treatment due to the presence of GBCA were minimal, and this work suggests that prospective in vivo evaluations of impact may not be necessary in this clinical site. Accounting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.

Assessment of MRI-Linac Economics under the RO-APM.

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (-89%) and pancreatic cancer (-83%). The total annual reimbursement discrepancy amounted to -78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of -47% for lung cancer and -46% for pancreatic cancer, mitigating the overall annual reimbursement difference to -54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM.

Therapeutic Radiographers at the Helm: Moving Towards Radiographer-Led MR-Guided Radiotherapy.

INTRODUCTION: Magnetic resonance-guided adaptive radiotherapy (MRgART) has the potential to improve treatment processes and outcomes for a variety of tumour sites; however, it requires significant clinical resources. Magnetic resonance linear accelerator (MR-linac) treatments require a daily multidisciplinary presence for delivery. To facilitate sustainable MRgART models, agreed protocols facilitating therapeutic radiographer (RTT)-led delivery must be developed to establish a service similar to conventional image-guided radiotherapy (IGRT). This work provides a clinical perspective on the implementation of a protocol-driven 'clinician-lite' MRgART workflow at one institution. METHODS: To identify knowledge, skills, and competence required at each step in the MRgART workflow, an interdisciplinary informal survey and needs assessment were undertaken to identify additional or enhanced skills required for MRgART, over and above those required for conventional cone-beam computed tomography-based IGRT. The MRgART pathway was critically evaluated by relevant professionals to encourage multidisciplinary input and discussion, allowing an iterative development of the RTT-led workflow. Starting with the simplest online adaptation strategy, consisting of a virtual couch shift and online replanning, clear guidelines were established for the delivery of radical prostate radiotherapy with a reduction in staff numbers present. RESULTS: The MRgART-specific skills identified included MRI safety and screening, MR image acquisition, MRI-based anatomy, multimodality image interpretation and registration, and treatment plan evaluation. These skills were developed in RTTs via tutorials, workshops, focussed self-directed reading, teaching of colleagues, and end-to-end workflow testing. After initial treatments and discussions, roles and responsibilities of the three professional groups (clinicians, RTTs, and physicists) have evolved to achieve a 'clinician-lite' workflow for simple radical prostate treatments. DISCUSSION: Through applying a definitive framework and establishing agreed threshold and action levels for action within anticipated treatment scenarios similar to those in cone-beam computed tomography-based IGRT, we have implemented a 'clinician-lite' workflow for simple adaptive treatments on the MR-linac. The responsibility for online plan evaluation and approval now rests with physicists and RTTs to streamline MRgART. Early evaluation of the framework after treatment of 10 patients has required minimal online clinician input (1.5% of 200 fractions delivered). CONCLUSION: A 'clinician-lite' prostate treatment workflow has been successfully introduced on the MR-linac at our institution and will serve as a model for other tumour sites, using more complex adaptive strategies. Early indications are that this framework has the potential to improve patient throughput and efficiency. Further identification and validation of roles and responsibilities such as online contouring, and more interactive online planning, will facilitate RTTs to fully lead in the online workflow as adaptive radiotherapy becomes ever more complex.