MR-guided Stereotactic Body Radiation Therapy Research Articles

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer – Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial

BackgroundDue to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methodsA total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. ResultsThere were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. ConclusionDaily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer

Background and purposeThis prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes.Materials and methodsThirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1–3 months), subacute (4–12 months), and late (> 12 months) phases.ResultsThe median follow-up was 390 days (range 28–823) and the median age was 70 years (range 58–82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6–15.3), and the median length of the spacer was 45.9 mm (range 16.8–62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4–99.8] for spacer vs. 97.8% [range 69.6–99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0–4.6] for spacer vs. 4.9 cc [range 0–12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains.ConclusionsMRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

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

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. 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. 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. 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.

Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases

PurposeWhile dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. MethodsThis is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). ResultsMedian follow up from MRgSBRT was 16.4 months (range [R]: 1.1–39 months). Median age was 67 years (R: 28–84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6–7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30–60 Gy) in 5–10 fractions with a median BED10 of 100 Gy (R: 48–132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0–10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. ConclusionsWe demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

Dosimetric predictors for genitourinary toxicity in MR-guided stereotactic body radiation therapy (SBRT): Substructure with fraction-wise analysis.

MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients. (1) To identify dosimetric predictors, potentially in combination with clinical parameters, of GU toxicity following SBRT by leveraging MRgRT to accurately monitor daily dose, beyond predicted dose calculated during planning. (2) Improve awareness of toxicity-sensitive bladder substructures, specifically the trigone and urethra. Sixty-nine prostate cancer patients (NCT04384770 clinical trial) were treated on a ViewRay MRIdian MRgRT system, with 40Gy prescribed to 95% of the PTV in over five fractions. Overall, 17 (24.6%) prostate patients reported acute grade 2 GU toxicity. The CTV, PTV, bladder, bladder wall, trigone, urethra, rectum, and rectal wall were contoured on the planning and daily treatment MRIs. Planning and daily treatment DVHs (0.1Gy increments), organ doses (min, max, mean), and organ volumes were recorded. Daily dose was estimated by transferring the planning dose distributions to the daily MRI based on the daily setup alignment. Patients were partitioned into a training (55) and testing set (14). Dose features were pre-filtered using a t-test followed by maximum relevance minimum redundancy (MRMR) algorithm. Logistic regression was investigated with regularization to select dosimetric predictors. Specifically, two approaches: time-group least absolute shrinkage and selection (LASSO), and interactive grouped greedy algorithm (IGA) were investigated. Shared features across the planning and five treatment fractions were grouped to encourage consistency and stability. The conventional flat non-temporally grouped LASSO was also evaluated to provide a solid benchmark. After feature selection, a final logistic regression model was trained. Dosimetric regression models were compared to a clinical regression model with only clinical parameters (age, baseline IPSS, prostate gland size, ADT usage, etc.) and a hybrid model, combining the best performing dosimetric features with the clinical parameters, was evaluated. Final model performance was evaluated on the testing set using accuracy, sensitivity, and specificity determined by the optimal threshold of the training set. IGA had the best testing performance with an accuracy/sensitivity/specificity of 0.79/0.67/0.82, selecting 12 groups covering the bladder (V19.8Gy, V20.5Gy), bladder wall (19.7Gy), trigone (15.9, 18.2, 43.3Gy), urethra (V41.4Gy, V41.7Gy), CTV (V41.9Gy), rectum (V8.5Gy), and rectal wall (1.2, 44.1Gy) dose features. Absolute bladder V19.8Gy and V20.5Gy were the most important features, followed by relative trigone 15.9 and 18.2Gy. Inclusion of clinical parameters in the hybrid model with IGA did not significantly change regression performance. Overall, IGA feature selection resulted in the best GU toxicity prediction performance. This exploratory study demonstrated the feasibility of identification and analysis of dosimetric toxicity predictors with awareness to sensitive substructures and daily dose to potentially provide consistent and stable dosimetric metrics to guide treatment planning. Further patient accruement is warranted to further assess dosimetric predictor and perform validation.

Improvement of 2D cine image quality using 3D priors and cycle generative adversarial network for low field MRI-guided radiation therapy.

Cine magnetic resonance (MR) images have been used for real-time MR guided radiation therapy (MRgRT). However, the onboard MR systems with low-field strength face the problem of limited image quality. To improve the quality of cine MR images in MRgRT using prior image information provided by the patient planning and positioning MR images. This study employed MR images from 18 pancreatic cancer patients who received MR-guided stereotactic body radiation therapy. Planning 3D MR images were acquired during the patient simulation, and positioning 3D MR images and 2D sagittal cine MR images were acquired before and during the beam delivery, respectively. A deep learning-based framework consisting of two cycle generative adversarial networks (CycleGAN), Denoising CycleGAN and Enhancement CycleGAN, was developed to establish the mapping between the 3D and 2D MR images. The Denoising CycleGAN was trained to first denoise the cine images using the time domain cine image series, and the Enhancement CycleGAN was trained to enhance the spatial resolution and contrast by taking advantage of the prior image information from the planning and positioning images. The denoising performance was assessed by signal-to-noise ratio (SNR), structural similarity index measure, peak SNR, blind/reference-less image spatial quality evaluator (BRISQUE), natural image quality evaluator, and perception-based image quality evaluator scores. The quality enhancement performance was assessed by the BRISQUE and physician visual scores. In addition, the target contouring was evaluated on the original and processed images. Significant differences were found for all evaluation metrics after Denoising CycleGAN processing. The BRISQUE and visual scores were also significantly improved after sequential Denoising and Enhancement CycleGAN processing. In target contouring evaluation, Dice similarity coefficient, centroid distance, Hausdorff distance, and average surface distance values were significantly improved on the enhanced images. The whole processing time was within 20ms for a typical input image size of 512 × 512. Taking advantage of the prior high-quality positioning and planning MR images, the deep learning-based framework enhanced the cine MR image quality significantly, leading to improved accuracy in automatic target contouring. With the merits of both high computational efficiency and considerable image quality enhancement, the proposed method may hold important clinical implication for real-time MRgRT.

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT)

BackgroundUltra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT–utilizing potentially fewer treatments–is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment.Methods/DesignA total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10–14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7–10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score.DiscussionFORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa.Trial registrationClinicaltrials.gov identifier: NCT04984343. Date of registration: July 30, 2021.Protocol version: 4.0, Nov 8, 2022.

Outcomes of Tolerability, Acute Toxicity and Quality of Life from MR-Guided Radiation Therapy (1.5T MR-Linac) for Liver Metastases in the MOMENTUM Study

Stereotactic body radiation therapy (SBRT) offers an important treatment option for metastatic liver tumors. The introduction of magnetic resonance (MR) guided SBRT has paved the way for optimal tumor visualization and daily plan adaptation. The purpose of this study is to review tolerability of MR-guided SBRT of liver metastases and to present early toxicity and quality of life outcomes. All patients with liver metastases who were treated on a 1.5T MR-Linac and enrolled in the MOMENTUM study (NTC04075305) were included. Patients were treated between April 2019 and December 2022 in 5 different institutes across 3 countries. Descriptive statistics were used to present the tolerability of treatment, toxicity (CTCAE v5.0) and quality of life outcomes (QLQ C30 and EQ 5D-5L) at baseline and 3 months after treatment. A total of 127 patients with liver metastases were included in the analysis. There were 64 females and 63 men, with a median age of 66 years (range 31 to 93). The median ECOG-score was 0 (range 0-2). The most common primary origin was colorectal cancer (66%), followed by bronchus and lung cancer (12%), with ocular melanoma, pancreatic and breast cancer being joint third (all 6-7%). Fractionation schedules ranged from 12 - 67.5 Gy in 2 - 12 fractions. The most commonly prescribed fractionation dose was 60 Gy in 3-5 fractions (53% and 13% respectively) and 50 Gy in 5 fractions (11%). Completion data was available for 116 patients. 112 patients (97%) received all fractions. 4 Patients (3%) did not complete treatment due to technical issues and 2 of the 4 receiving no treatment on the MR-Linac. Physician reported toxicity at 3 months was recorded for 82 patients (66%). No grade 4 or 5 toxicities were reported. There were 12 grade 3 toxicities reported in 6 (7%) patients with 5 deemed radiation therapy related (Table 1) and 34 grade 2 toxicities in 21 (26%) patients. We have presented the largest cohort (to our knowledge) of 127 patients treated using 1.5 Tesla MR Guidance for metastatic liver tumors. 97% of treatments were completed successfully with all treatments being well tolerated. Acute grade 3 toxicity was reported in 7% of patients with no grade 4 or 5 toxicities present. These outcomes suggest radiotherapy on the MR-Linac is a safe and promising treatment for patients with liver metastases. Additional prospective follow up is ongoing for late toxicity events and long-term control data. Table 1: Grade ≥3 toxicity at 3 months related to radiation therapy (total No. of patients was 82) There was QLQ-C30 data on 89 patients at baseline and on 62 patients at 3 months. At 3 months the median score was worse for physical functioning, VAS score and pain.

Clinical outcomes of patients with unresectable primary liver cancer treated with MR-guided stereotactic body radiation Therapy: A Six-Year experience.

Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) with optional online adaptation has shown promise in delivering ablative doses to unresectable primary liver cancer. However, there remain limited data on the indications for online adaptation as well as dosimetric and longer-term clinical outcomes following MRgSBRT. Patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CCA) who completed MRgSBRT to 50Gy in 5 fractions between June of 2015 and December of 2021 were analyzed. The necessity of adaptive techniques was evaluated. The cumulative incidence of local progression was evaluated and survival and competing risk analyses were performed. Ninety-nine analyzable patients completed MRgSBRT during the study period and 54% had planning target volumes (PTVs) within 1cm of the duodenum, small bowel, or stomach at the time of simulation. Online adaptive RT was used in 53% of patients to correct organ-at-risk constraint violation and/or to improve target coverage. In patients who underwent adaptive RT planning, online replanning resulted in superior target coverage when compared to projected, non-adaptive plans (median coverage≥95% at 47.5Gy: 91% [IQR: 82-96] before adaptation vs 95% [IQR: 87-99] after adaptation, p<0.01). The median follow-up for surviving patients was 34.2months for patients with HCC and 10.1months for patients with CCA/cHCC-CCA. For all patients, the 2-year cumulative incidence of local progression was 9.8% (95% CI: 1.5-18%) for patients with HCC and 9.0% (95% CI: 0.1-18) for patients with CCA/cHCC-CCA. Grade 3 through 5 acute and late clinical gastrointestinal toxicities were observed in<10% of the patients. MRgSBRT, with the option for online adaptive planning when merited, allows delivery of ablative doses to primary liver tumors with excellent local control with acceptable toxicities. Additional studies evaluating the efficacy and safety of MRgSBRT in the treatment of primary liver cancer are warranted.

Automated Analysis of Treatment Log Files and Videos for MR-Guided Stereotactic Body Radiation Therapy Treatments of Thoracic and Abdominal Tumors

<h3>Purpose/Objective(s)</h3> MR-guided stereotactic body radiation therapy (MRgSBRT) is a novel method of treating mobile tumors with robust real-time gating and on-table adaptive planning. Delivery log files and cine videos of the treatment generated by the software system can be a rich source of information for assessing MRgSBRT treatment sessions. We hypothesized that developing scripts for automated review of MRgSBRT treatments using delivery logs and cine videos would be feasible. We have included a summary of our findings from our initial experience using this automated analysis. <h3>Materials/Methods</h3> We conducted a retrospective review of patients undergoing MRgSBRT for treatment of liver, lung, and pancreas tumors. Custom Python scripts were written to automatically extract treatment delivery information from log files and export data neatly into to a spreadsheet. A separate Python script was written to extract information from delivery cine videos using optical character recognition (OCR), color thresholding, and morphological processing as well. <h3>Results</h3> Using our automated system we were able to extract the following data points from the log files: treatment site, date and time of treatment, tracking algorithm configuration, average treatment duration, total dose, fraction (fx) number, MU per fx, couch shifts, and need for plan re-optimization. Additionally, through automated analysis of treatment cine video files we were able to extract frame by frame information for tracking structure centroid displacement, beam on/off status, frame-frame similarity, and tracking confidence (TC) over the course of treatment. Table 1 is an example of the data output. <h3>Conclusion</h3> Automated analysis of MRgSBRT delivery log files and log videos is feasible and can serve as a rich resource for QA/QI to improve treatment efficiency on an MR-LINAC by quantifying a multitude of measurable parameters and formulating strategies to address any unrealized bottlenecks in the process. Future plans include expanding our automation to examine total patient time on table, monitor units per beam segment, and predicting internal tumor volumes (ITV) based on tracking target displacement obtained from the delivery videos.

Dosimetric Effect of Respiratory Phase in MR-Guided SBRT for Locally Advanced Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Dose escalation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) has traditionally been limited by organs-at-risk (OARs) tolerance; however, MR-guided SBRT (MRgSBRT) is currently being evaluated for dose escalation in multi-institutional trials. This novel treatment method incorporates soft tissue gating and on-table adaptive planning to achieve optimal dosimetry. Moreover, respiratory gating has previously been employed to minimize dose to OARs for tumors that sit close to the diaphragm. It can be inferred that the superior position of the diaphragm in end exhale breath hold (EE) allows for greater abdominal organ separation than in deep inspiration breath hold (DI). Therefore, we hypothesized that patients (pts) treated during EE for LAPC would demonstrate favorable treatment planning metrics including increased target coverage and decreased monitor unit delivery compared to pts treated in DI. <h3>Materials/Methods</h3> Five pts with LAPC previously treated with MRgSBRT were included in this analysis. For each pt, at the time of simulation, a CT scan was performed for heterogeneity corrections followed by two planning MRI scans: one in end exhale (MR_EE) and one in deep inspiration (MR_DI). All pts were ultimately treated in DI. For this study, both MR_EE and MR_DI scans were anonymized for contouring of targets and OARs. CTV was defined as the gross tumor (GTV) plus elective nodal coverage of the superior mesenteric (SM) and celiac axis (CA) nodes. PTV was defined as a 3 mm expansion on the CTV. The prescription dose was 50 Gy in 5 fractions every other day. Each plan was normalized by taking one of the luminal GI OARs (stomach, duodenum, small bowel, or large bowel) to the maximum tolerance of 33Gy to 0.5cc. Treatment plans were created using 18-21 beams per plan with a constant number of available beams per patient. A two-tailed t-test of equal variance was used to compare CTV coverage, PTVopt coverage, and monitor units per fraction (MU/fx) between the plans created on the MR_EE and MR_DI scans. <b>Results:</b> <h3>Conclusion</h3> Dose-escalated MRgSBRT for LAPC results in adequate target coverage while also respecting OAR tolerances. However, we were not able to demonstrate any statistically significant difference between the two breath hold techniques (EE vs DI) for CTV coverage, PTVopt coverage or monitor units per fraction for our cohort. Therefore, we recommend treating using the most comfortable and reproducible breath hold per pt. Further work is needed to characterize other factors such as patient compliance and gating efficiency.

An Essential Treatment Pattern of Lung Cancer: Magnetic Resonance-Guided Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) has emerged as an important treatment for non-resectable lung cancer. MR-Linac can offer superior soft-tissue contrast, have the ability to visualize cancer physiology and daily on-table treatment adaptation. Obviously combined SBRT with MR-Linac holds the promise to improve the accuracy of radiotherapy and reduce the toxicity of organs-at-risk (OAR). However, data on treatment effect and patient acceptance is still limited. <h3>Materials/Methods</h3> Between July 2019 and October 2021,14 patients with lung cancer were treated with an MRI-Linac guided SBRT, of them, 6 in left upper lobe, 1 in left lower lobe, 2 in right upper lobe and 5 in right lower lobe. The CT simulation used a Siemens big-bore CT scanner (syngo CT VA62A) for all patients. All patients were treated with step and shoot intensity modulated radiotherapy (IMRT). The online plan was created while the patient was on the treatment table and based on the online MRI images; pre-treatment CT was deformably registered to the online MRI to obtain position error. All patients used adapt to position (ATP) workflow. The curative effect and adverse reactions in the process of treatment need to be paid close attention to, and the adverse reactions should be treated and recorded in time. <h3>Results</h3> Fourteen patients (with n=2 metastases; n=12 primary tumor) received MR-guided SBRT. Median prescribed does was 60Gy(range:54Gy-70Gy) and median planning target volume was 28.8cc (range:11.1-93.4cc). Two patients occurred grade I bone marrow suppression and two occurred grade II bone marrow suppression. One patient occurred grade I gastrointestinal toxicity. No patient occurred grade III or higher toxicity. Only one patient developed left lung recurrence and left hilar lymph node metastasis ten months after treatment, one patient was not re-examined, and others were controlled locally. <h3>Conclusion</h3> In summary, MR-guided SBRT of lung cancer is well-effective and well-accepted. The results are promising that it holds with prominent local control and mild adverse events. The influence of magnetic field on dosimetry remains to be studied. The relevant work is also conducted.

Multi-Institutional Experience of MR-Guided Stereotactic Body Radiation Therapy for Adrenal Gland Metastases

<h3>Purpose/Objective(s)</h3> While dose-escalation is associated with improved local control (LC) for adrenal gland metastases (AGM), the proximity of gastrointestinal (GI) structures limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The relative advantages of magnetic resonance guided SBRT (MRgSBRT), including tumor tracking, treatment under breath hold, and online plan adaptation, create the potential for safe dose escalation. The present study investigated the efficacy and safety of MRgSBRT for treatment of AGMs across multiple institutions. <h3>Materials/Methods</h3> This is a multi-institutional retrospective review of 57 consecutive patients who underwent MRgSBRT on a 0.35-T MR Linac to 61 AGMs from April 2019 to September 2021. Univariate analysis (UVA) with the Kaplan-Meier (KM) method was used to estimate time-to-event outcomes, including overall survival (OS), progression-free survival (PFS), and LC, with group differences compared by log-rank testing. Median follow up was calculated with the reverse KM method. <h3>Results</h3> Median follow up was 12.2 months (95% CI 8.1-17.2 months). Median age at the time of SBRT was 67 years (range: 28-84 years). Primary histologies included non-small cell lung cancer (N=38), renal cell carcinoma (N=6), and melanoma (N=5), amongst others. Most AGMs were left-sided (N=32) with a median maximum diameter of 2.7cm (range: 0.6-7.6cm) treated to a median total dose of 50 Gy (range: 30-60 Gy) in 5-10 fractions with a median BED₁₀ 100 Gy (range: 48-132 Gy). Forty-five cases (74%) required adaptation, more frequently in left-sided lesions due to the proximity of the stomach and small bowel (88% vs 59%). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N=1) and 40 Gy in 5 fractions (N=2). One-year LC, PFS, and OS were 90%, 40%, and 76%, respectively. On UVA, only melanoma histology predicted for inferior 1-year LC (53% vs 92%, <i>p</i>=0.022). There was a nonsignificant improvement in LC for BED₁₀ of 132 Gy (1-year LC 100% vs 87%, <i>p</i>=0.148). No patients who received BED₁₀ 132 Gy (N=13) experienced local failure. There were no instances of grade 3+ acute or late toxicity. <h3>Conclusion</h3> Our early outcomes demonstrate MRgSBRT achieves favorable LC and no grade 3+ toxicity despite prescribing a median BED₁₀ of 100 Gy to targets in proximity of GI organs at risk. The unique advantages of MR guidance and online adaptive replanning may be especially beneficial for achieving safe dose escalation of radioresistant histologies such as melanoma.

Economic Evaluations of Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A Systematic Review.

Objectives: This review systematically summarizes the evidence on the economic impact of magnetic resonance image-guided RT (MRIgRT). Methods: We systematically searched INAHTA, MEDLINE, and Scopus up to March 2022 to retrieve health economic studies. Relevant data were extracted on study type, model inputs, modeling methods and economic results. Results: Five studies were included. Two studies performed a full economic assessment to compare the cost-effectiveness of MRIgRT with other forms of image-guided radiation therapy. One study performed a cost minimization analysis and two studies performed an activity-based costing, all comparing MRIgRT with X-ray computed tomography image-guided radiation therapy (CTIgRT). Prostate cancer was the target condition in four studies and hepatocellular carcinoma in one. Considering the studies with a full economic assessment, MR-guided stereotactic body radiation therapy was found to be cost effective with respect to CTIgRT or conventional or moderate hypofractionated RT, even with a low reduction in toxicity. Conversely, a greater reduction in toxicity is required to compete with extreme hypofractionated RT without MR guidance. Conclusions: This review highlights the great potential of MRIgRT but also the need for further evidence, especially for late toxicity, whose reduction is expected to be the real added value of this technology.

Accumulated bladder wall dose is correlated with patient-reported acute urinary toxicity in prostate cancer patients treated with stereotactic, daily adaptive MR-guided radiotherapy

Background and purposeMagnetic resonance (MR)-guided linear accelerators (MR-Linac) enable accurate estimation of delivered doses through dose accumulation using daily MR images and treatment plans. We aimed to assess the association between the accumulated bladder (wall) dose and patient-reported acute urinary toxicity in prostate cancer (PCa) patients treated with stereotactic body radiation therapy (SBRT). Materials and methodsOne-hundred-and-thirty PCa patients treated on a 1.5 T MR-Linac were included. Patients filled out International Prostate Symptom Scores (IPSS) questionnaires at baseline, 1 month, and 3 months post-treatment. Deformable image registration-based dose accumulation was performed to reconstruct the delivered dose. Dose parameters for both bladder and bladder wall were correlated with a clinically relevant increase in IPSS (≥ 10 points) and/or start of alpha-blockers within 3 months using logistic regression. ResultsThirty-nine patients (30%) experienced a clinically relevant IPSS increase and/or started with alpha-blockers. Bladder D5cm3, V10–35Gy (in %), and Dmean and Bladder wall V10–35Gy (cm3 and %) and Dmean were correlated with the outcome (odds ratios 1.04–1.33, p-values 0.001–0.044). Corrected for baseline characteristics, bladder V10–35Gy (in %) and Dmean and bladder wall V10–35Gy (cm3 and %) and Dmean were still correlated with the outcome (odds ratios 1.04–1.30, p-values 0.001–0.028). Bladder wall parameters generally showed larger AUC values. ConclusionThis is the first study to assess the correlation between accumulated bladder wall dose and patient-reported urinary toxicity in PCa patients treated with MR-guided SBRT. The dose to the bladder wall is a promising parameter for prediction of patient-reported urinary toxicity and therefore warrants prospective validation and consideration in treatment planning.

Initial observation of contrast profiles for 3D and 2D MRI sequences in MR-guided radiation therapy for locally advanced pancreatic cancer.

541 Background: MR-guided stereotactic body radiation therapy (MR-SBRT) is a novel method of treating mobile tumors with soft-tissue gating and on-table adaptive planning. In our experience using the ViewRay MRIdian system (VR) for treating locally advanced pancreatic cancer (PA) with MR-SBRT, the true-fast imaging with steady-state free precession (TRUFI) sequences on the VR impart differing intensities for relevant structures seen on the pre-treatment high resolution 3D MRI (3D MRI) versus the real-time 2D cine MRI (2D cine) used for target tracking. Since these variations can confound target tracking selection, we propose that an understanding of the differing contrast profiles could improve selection of tracking structures and optimize treatment delivery. Methods: We retrospectively reviewed both 3D MRI and 2D cine images for patients (pts) with PA (n =20) treated on the VR. At simulation, an appropriate tracking target was identified and contoured on a single 3mm sagittal slice of the 3D MRI. This sagittal slice was directly compared to the registered 7mm 2D cine to identify structures with notable discrepancies in signal intensity. The 3D MRI was then explored in additional planes to confirm structure identities. For quantitative verification of the clinically observed differences, the pixel intensity distributions of 3D MRI and 2D cine DICOM image datasets were statistically compared. Results: In all pts reviewed, arteries (aorta, celiac, SMA) appeared with similar contrast profiles on both images. However, veins (portal vein, SMV) appeared hypointense on 3D MRI but hyperintense on 2D cine. Biliary structures appeared hyperintense on 3D MRI but only mildly hyperintense on 2D cine. The pixel intensity distributions extracted from 3D MRI and 2D cine images were confirmed to differ significantly (two sample Kolmogorov-Smirnov test; test statistic =0.40; p &lt; 0.001). Conclusions: There are significant variations in image intensity between the initial treatment planning 3D MRI and the immediate pre-treatment 2D cine obtained with the VR. Understanding these discrepancies can guide radiation oncologists in choosing optimal tracking targets. Future work will focus on identifying the particular causes and frequencies of target tracking failures and exploring alternative tracking algorithms using artificial intelligence which could ultimately allow for VMAT on the ViewRay system.

Pathological outcomes of pancreatic adenocarcinoma (PA) after preoperative high biological effective dose (BED) magnetic resonance image-guided radiation therapy (MRgRT).

573 Background: Pre-operative radiotherapy (RT) for PA has the potential to reduce positive surgical margin rates and increase pathologic tumor response, which has been associated with improved survival. Increasing the BED can improve local control and overall survival for patients with unresectable PA. Use of stereotactic body radiation therapy (SBRT) to achieve a higher BED has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by MRgRT. We describe our use of MRgRT prior to potentially curative resection of localized PA. Methods: We performed a single institution retrospective analysis of all patients with localized PA who received high BED SBRT on the MR Linac followed by surgical resection with curative intent. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria (CAP-TRG), ranging from CAP 0 indicating pathologic complete response to CAP grade 3 indicating no response. Ordinal logistic regression model was used to assess the association between time from RT to surgery and TRG. Follow up included MRI or CT scans at least every three months. Results: We analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received high BED MRgRT followed by surgical resection. Median age at diagnosis was 68 years (34 - 86). Most patients received chemotherapy (80.8%) prior to RT, with 81% of these receiving FOLFINIRNOX and 19% receiving gemcitabine/nab-paclitaxel. All patients received MR-guided high BED SBRT to a median dose of 50 Gy (40 - 50) in 5 fractions. On-table adaptive replanning was performed in 88% of patients, with 74% having all 5 fractions adapted. No acute grade 2+ toxicity associated with RT was observed. The median time to resection was 50 days (37 – 115), and the procedure types included: Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Complete (0) or near-complete (1) pathologic response was observed in 35% of cases and the time from RT to surgery was positively associated with TRG (R2= 0.22, p = 0.0003). The median follow-up after RT was 16.5 months (3.9- 26.2) during which 9 patients recurred, and 3 patients died of disease. The derived median progression-free survival from RT was 13.2 months. Conclusions: These initial pathology outcomes following high BED MR-guided SBRT are encouraging and suggest that the time from SBRT to surgical resection is associated with response. This finding is consistent with results from other preoperative GI tumor sites and results from prospective studies using high BED SBRT with MRI guidance in combined modality therapy against PA are eagerly awaited.

Online adaptive MR-guided stereotactic radiotherapy for unresectable malignancies in the upper abdomen using a 1.5T MR-linac

Background Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. Material and methods Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective ‘Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac’ (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. Results Twenty-five consecutive patients with a median follow-up time of 8 (range 4–23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30–74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. Discussion Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies.

Clinical Outcomes of Patients With Hepatocellular Carcinoma Treated With MR-guided Stereotactic Body Radiation Therapy With Online Adaptive Planning

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) for primary liver tumors may be limited by proximity to organs-at-risk (OAR). MR-guided SBRT (MRgSBRT) with online adaptive planning has shown promise in delivering ablative doses to the liver safely. We reported the clinical outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with MRgSBRT with online adaptive planning. <h3>Materials/Methods</h3> Patients with unresectable HCC treated with MRgSBRT between 2015 and 2019 with minimum 3 months of follow-up were retrospectively reviewed at a single institution. Local progression was defined by mRECIST. Survival analysis was performed with the Kaplan-Meier method. Toxicity was assessed using Common Terminology Criteria for Adverse Events Version 5. <h3>Results</h3> Thirty-five patients with a total of 41 HCC lesions, all treated to 50 Gy in 5 fractions, were analyzed. The median tumor size was 2.9 cm (IQR: 2.0-4.5). Barcelona-Clinic Liver Cancer (BCLC) Staging was 0, A, B, C, and D in 2 (6%), 8 (23%), 18 (51%), 6 (17%), and 1 (3%), respectively. Twenty-seven (77%) patients had previous liver-directed therapy (chemoembolization, radioembolization, cryoablation) to the target lesion with evidence of residual disease or progression on follow-up imaging. The median follow-up from completion of MRgSBRT was 21 months (IQR, 10-34). Online adaptive planning was performed for 19% of all fractions. It was done due to exceeding dose constraints to OARs in 26/33 (79%) fractions, and to improve tumor coverage in 7/33 (21%) fractions. Clinical response assessed at a median of 2.4 months (IQR: 2.0-3.0) after MRgSBRT revealed a complete response in 26% (9/35), partial response in 23% (8/35), stable disease in 40% (14/35), and progressive disease in 9% (3/35). One (3%) patient did not have repeat imaging at the time of initial clinical follow-up. The 1- and 2-year freedom from local progression (FFLP) rates were both 91% (95% CI: 83-100%). The 1- and 2-year freedom from progression elsewhere in the liver (FFELP) rates were 58% (95% CI: 44-78%) and 50% (95% CI: 35-72%), respectively. The 1- and 2-year overall survival were 83% (95% CI: 71-96%) and 58% (95% CI: 43-77%), respectively. The most commonly noted acute grade ≤2 clinical toxicities were fatigue, abdominal pain, and nausea. Four patients had grade 3 toxicity: 1 (3%) ascites, 1 (3%) portal hypertension, 2 (6%) hepatic failure. One patient (3%) had grade 4 gangrenous cholecystitis. Eleven (31%) patients later underwent an orthotopic liver transplant. <h3>Conclusion</h3> MRgSBRT with online adaptive planning allows delivery of ablative doses to HCC with excellent local control and acceptable toxicity. Additional studies evaluating the role of MRgSBRT in the treatment of liver tumors are warranted.

Target Coverage, Organ at Risk Metrics, and Tumor Control for Metastases to the Pancreas Treated With Adaptive MR-Guided Stereotactic Body Radiation Therapy

Metastases to the pancreas (MPs) are difficult to treat with radiation therapy (RT) due to respiratory and bowel motion and proximity to critical organs at risk (OARs). Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) may improve tumor coverage and OAR sparing through motion control with breath hold gating and continuous MR imaging during treatment, and the option for daily online adaptive replanning (ARP) to account for changes in tumor and/or OAR position. We evaluated the need for online adaptive MRgSBRT and its effect on target coverage, OAR metrics, and tumor control in patients with MPs.In this IRB-approved retrospective study, we reviewed the records of patients with MPs treated with MRgSBRT between July 2019 and January 2021. Patients were identified from a prospectively maintained database. Data were collected regarding dose to targets and OARs, use and rationale for ARP, toxicity, and outcomes. Treatment response was defined as a decrease in size of the treated MP. Local failures were defined as recurrences within the RT field. Descriptive statistics were used.We identified 8 MPs in 6 patients. Median age was 70 years (range, 61-88). Patients had oligoprogressive or oligometastatic renal cell carcinoma (n = 3), carcinoid (n = 1), hepatocellular carcinoma (n = 1), and lung adenocarcinoma (n = 1). The median time from diagnosis to development of metastatic disease was 17 months (range, 0-105 months) and to treatment of the MP was 36 months (range, 7-230 months). All patients received 40 Gy in 5 fractions with breath hold technique. The median GTV was 8.5 cc (range, 2.2-132.8 cc) and PTV was 27.7 cc (range, 8.3-175.7 cc). 35/40 (87%) fractions required ARP, necessary to meet stomach and duodenal metrics in 11 (27%) and 16 (40%) fractions, respectively. The mean stomach, duodenal, and PTV metrics before and after ARP are reported in Table 1. On average, ARP increased the PTV coverage by 4.9% and decreased the stomach V33, stomach V35, and duodenum V33 by 0.61 cc, 0.31 cc, and 1.10 cc, respectively. At a median follow-up of 5.0 months, 6/8 (75%) lesions had a partial response. There were no local failures. There was one distant failure 27 days after treatment. One patient developed a grade 2 pyloric ulcer which resolved with medical management. There were no other ≥ grade 2 toxicities.In this study, ARP was necessary in most MRgSBRT treatments to MPs. Adaptive MRgSBRT improved PTV coverage and OAR metrics, and it provided high rates of tumor control with minimal toxicity. Further study in larger patient populations and in peripancreatic metastases is needed.