MRI-guided Adaptive Radiotherapy Research Articles

Surrogate gating strategies for the Elekta Unity MR-Linac gating system.

MRI-guided adaptive radiotherapy can directly monitor the anatomical positioning of the intended target during treatment with no additional imaging dose. Elekta has recently released its comprehensive motion management (CMM) solution that enables automatic radiation beam-gating on the Unity MR-Linac. Easily visualized targets that are distinct from the surrounding anatomy can be used to drive automatic gating decisions from the MRI cine imaging. However, poorly visualized targets can compromise the tracking and gating capabilities and may require surrogate tracking structures. This work presents strategies to generate robust tracking surrogates for a variety of treatment sites, enabling a wider application of CMM. Surrogate tracking strategies were developed from a cohort of patients treated using the CMM system on the Unity MR-Linac for treatment sites of the lung, pancreas, liver, and prostate. These sites posed challenging visualization or tracking of the primary target thereby compromising the tracking accuracy. Surrogate structures were developed using site-specific strategies to improve the imaging textured detail within the tracking volume while avoiding the dynamic overwhelming hypo- or hyper-intense anatomical structures. These surrogate volumes were applied within the anatomical positioning monitoring system as a proxy that drove the CMM gating decisions on the treatment unit. Robust site-specific surrogate structures were developed. Surrogate tracking structures for centrally located thoracic targets were created by expanding the target peripherally away from the heart and great vessels and into the lung. Pancreas surrogates required a vertically expanded column intersecting with the inferior liver edge. For the liver and prostate, surrogate structures consisted of a uniform expansion of the target, with liver surrogates intersecting the proximal liver edge or diaphragm while avoiding nearby ribs. These surrogate strategies have enabled the gating of complex moving targets among different treatment sites at our institution.

P188 Stereotactic MRI-guided adaptive radiotherapy for renal tumors in a solitary kidney

P188 Stereotactic MRI-guided adaptive radiotherapy for renal tumors in a solitary kidney

A patient-specific auto-planning method for MRI-guided adaptive radiotherapy in prostate cancer

Background and purposeFast and automated generation of treatment plans is desirable for magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). This study proposed a novel patient-specific auto-planning method and validated its feasibility in improving the existing online planning workflow. Materials and methodsData from 40 patients with prostate cancer were collected retrospectively. A patient-specific auto-planning method was proposed to generate adaptive treatment plans. First, a population dose-prediction model (M0) was trained using data from previous patients. Second, a patient-specific model (Mps) was created for each new patient by fine-tuning M0 with the patient’s data. Finally, an auto plan was optimized using the parameters derived from the predicted dose distribution by Mps. The auto plans were compared with manual plans in terms of plan quality, efficiency, dosimetric verification, and clinical evaluation. ResultsThe auto plans improved target coverage, reduced irradiation to the rectum, and provided comparable protection to other organs-at-risk. Target coverage for the planning target volume (+0.61 %, P = 0.023) and clinical target volume 4000 (+1.60 %, P < 0.001) increased. V2900cGy (−1.06 %, P = 0.004) and V1810cGy (−2.49 %, P < 0.001) to the rectal wall and V1810cGy (−2.82 %, P = 0.012) to the rectum were significantly reduced. The auto plans required less planning time (−3.92 min, P = 0.001), monitor units (−46.48, P = 0.003), and delivery time (−0.26 min, P = 0.004), and their gamma pass rates (3 %/2 mm) were higher (+0.47 %, P = 0.014). ConclusionThe proposed patient-specific auto-planning method demonstrated a robust level of automation and was able to generate high-quality treatment plans in less time for MRIgART in prostate cancer.

Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion. A regression analysis was performed to measure how the volume of air within the rectum might further impact rectal dose secondary to the electron return effect (ERE). One hundred percent of CTV target objectives were achieved on the MRI taken prior to beam-on-time. The post-delivery MRI showed that high-dose CTV coverage was achieved in 90% of sub-fractions (each fraction is delivered in two sub-fractions) in the 2-fraction cohort and in 88% of fractions the 5-fraction cohort. Rectal D1 cm3 was the most exceeded constraint; three patients exceeded the D1 cm3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm3 < 36 Gy in the 5-fraction cohort. The volume of rectal gas within 1 cm of the prostate was directly proportional to the increase in rectal D1 cm3, with a strong (R = 0.69) and very strong (R = 0.90) correlation in the 2-fraction and 5-fraction cohort respectively. Dose delivery specified in HERMES is feasible, although for some patients delivered doses to both target and OARs may vary from those planned.

Evaluation and mitigation of deformable image registration uncertainties for MRI-guided adaptive radiotherapy.

We evaluate the performance of a deformable image registration (DIR) software package in registering abdominal magnetic resonance images (MRIs) and then develop a mechanical modeling method to mitigate detected DIR uncertainties. Three evaluation metrics, namely mean displacement to agreement (MDA), DICE similarity coefficient (DSC), and standard deviation of Jacobian determinants (STD-JD), are used to assess the multi-modality (MM), contour-consistency (CC), and image-intensity (II)-based DIR algorithms in the MIM software package, as well as an in-house developed, contour matching-based finite element method (CM-FEM). Furthermore, we develop a hybrid FEM registration technique to modify the displacement vector field of each MIM registration. The MIM and FEM registrations were evaluated on MRIs obtained from 10 abdominal cancer patients. One-tailed Wilcoxon-Mann-Whitney (WMW) tests were conducted to compare the MIM registrations with their FEM modifications. For the registrations performed with the MIM-CC, MIM-MM, MIM-II, and CM-FEM algorithms, their average MDAs are 0.62±0.27, 2.39±1.30, 3.07±2.42, 1.04±0.72mm, and average DSCs are 0.94±0.03, 0.80±0.12, 0.77±0.15, 0.90±0.11, respectively. The p-values of the WMW tests between the MIM registrations and their FEM modifications are less than 0.0084 for STD-JDs and greater than 0.87 for MDA and DSC. Among the three MIM DIR algorithms, MIM-CC shows the smallest errors in terms of MDA and DSC but exhibits significant Jacobian uncertainties in the interior regions of abdominal organs. The hybrid FEM technique effectively mitigates the Jacobian uncertainties in these regions.

Narrative review of the utility of magnetic resonance imaging in radiotherapy for cervical cancer.

In radiotherapy (RT) for locally advanced cervical cancer, high soft tissue contrast on magnetic resonance imaging (MRI) can ensure accurate delineation of target volumes (TVs) and optimal dose distribution to the RT target and organs at risk (OAR). MRI-guided adaptive RT (MRIgART) is a novel technology that revises RT plans according to anatomical changes occurring throughout the treatment to improve target coverage and minimise OAR toxicity. This review aims to assess the evidence and gaps of MRI use in RT planning and MRIgART in the treatment of cervical cancer, as well as challenges in its clinical implementation. Ovid Medline and PubMed were searched using keywords for MRI in RT for cervical cancer. After applying the inclusion and exclusion criteria, the initial search was deduced to 32 studies. A total of 37 final studies were reviewed, including eight additional articles from references. In the primary studies, TVs and organ motion were assessed before, during, and after treatment. MRI was used to investigate dose distribution and therapeutic response to the treatment in association with its outcome. Lastly, rationales for MRIgART were evaluated. It was concluded that MRI enables accurate target delineation, assessment of organ motion and interfraction changes, and monitoring of treatment response through dynamic parameters. Enhanced target coverage and reduced OAR irradiation through MRIgART can improve local control and the overall outcome, although its rationales against the logistical challenges need to be evaluated on further research.

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

BackgroundMagnetic 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).MethodsEighteen 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.ResultsThe 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.ConclusionsThe 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.

A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging.

An artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care. In collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics. The observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs. This study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

MRI Guided Adaptive Radiotherapy (MRgART) in Primary and Metastatic Liver Lesions

The role of stereotactic body radiotherapy (SBRT) in the management of primary hepatic and metastatic tumors has increased significantly over the past few years. MR-Linac is rapidly gaining evidence in the delivery of ablative doses using MR guided adaptive radiotherapy (MRgART) with improved accuracy and dose coverage to the lesions. We report local control and toxicity of patients with primary and metastatic liver lesions treated with MR guided adaptive SBRT. All patients were treated with MRgART on the Unity 1.5T MR Linacs at two institutions and consented to the ADAPT-MRL study (1). A 4DCT and MRI with abdominal compression were obtained at simulation and the primary MRI sequence used for online treatment included a T2 3D navigated scan. A balanced turbo field echo (btFFE) 2D cine motion scan was also acquired at every fraction to determine movement of the tumor to aid in internal target volume margin. All plans were treated with SBRT prescribed to 3-5 alternate daily fractions. Acute toxicity was reported according to Common Terminology Criteria for Adverse Events version 5 (CTCAE) v.5. Patient demographics, prescribed dose fractionation, acute toxicity and clinical response at 6 months were analyzed. Clinical response to treatment was measured according to RECIST criteria 1.1. Between February 2021 to January 2023 a total of 30 patients were treated with 149 fractions to the liver. Patients were majority male (70%) with a median age of 66 (range 36-83). 16 patients were treated for primary hepatocellular carcinoma (HCC) of the liver and 14 patients for metastatic liver lesions. The median prescribed dose was 48 Gy (range 30-50Gy) in median 5 fractions (range (3-5 fractions). All patients completed treatment with no interruptions. The mean time from 'patient setup' to 'beam-off' was 52.6 minutes (range 37-73 minutes). Data on acute toxicity at 3 month follow up was available for 28 patients. Of these patients 7/28 (25%) had grade 1 or 2 toxicity and no >/ = grade 3 toxicity was reported. Clinical response at 6 months was available for 18 patients and showed complete response in 44% (8/18), partial response in 22% (4/18), stable disease in 22% (4/18) and progressive disease in 11.1% (2/18). Our experience on MRgART to the liver has shown good local control and minimal acute toxicity in the treatment of primary and metastatic liver lesions. We continue to collect data on patient reported outcomes, clinical response and toxicity to determine the feasibility and safety of this system.

Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

Randomized Trial of Five or Two MRI-guided Adaptive Radiotherapy Treatments for Prostate Cancer (FORT)

The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 - 1 3. IPSS < 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP < 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from "no problem" to "very small problem") or one of the symptoms worsening by 2 levels (i.e., loose stool change from "no problem" to "small problem"). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Twenty patients. To be determined. To be determined.

Randomized trial of five or two MRI-guided adaptive radiotherapy treatments for prostate cancer (FORT).

TPS399 Background: The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged &gt; 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 – 1 3. IPSS &lt; 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP &lt; 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Eleven patients. Clinical trial information: NCT04984343 .

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9months and 11.6months, respectively. Calculated from SMART, the median PFS was 2.4months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

A pilot study of same-day MRI-only simulation and treatment with MR-guided adaptive palliative radiotherapy (MAP-RT)

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3–5 toxicities occurred.

Estimation of Cumulative Organ Maximum Dose and Confidence Intervals for MRI-Guided Adaptive Radiotherapy of Abdominal Cancer

<h3>Purpose/Objective(s)</h3> The maximum dose (Dmax), e.g., D0.03cc (dose to 0.03cc volume), of adjacent organs at risk (OARs) is a primary dose-limiting constraint in MRI-guided adaptive radiotherapy (MRgART) of abdominal cancer. We utilized inverse consistency error (ICE) maps to estimate voxel-wise uncertainties in deformable image registration (DIR) based dose accumulation (DDA) and confidence intervals in cumulative OARs Dmax during MRgART for pancreatic cancer. <h3>Materials/Methods</h3> Motion-average reference (first fraction) and subsequent daily MRIs, collected in MRgART for five pancreatic cancer patients treated with 33 Gy in 5 fractions on a 1.5T MR-Linac, were registered using a free-form DIR algorithm based on feature similarity scoring metrics and were used to accumulate daily doses. Forward and reverse DIRs were performed, and ICE maps were calculated in the reference image. The correlation between ICE and actual registration error (RE) was assessed by identifying anatomical landmarks (63) in a reference-daily image pair and measuring the landmark REs (after forward-DIR) and ICEs (after forward and reverse DIRs). To account for the deformation vector field spatial uncertainty affecting the DDA, for each voxel in the reference image we associated a cloud of dose grid points centered at the voxel landing coordinates in the daily image with a radius proportional to the ICE length. We considered that the cloud would encompass the "true" registration point with a high likelihood. The uncertainty in the dose mapped to each voxel from each fraction was determined as the standard deviation of the grid point doses within the cloud. The maxima and minima of the dose distributions were computed from the cumulative uncertainties, and confidence intervals for Dmax were determined. <h3>Results</h3> The measured REs and ICEs for landmarks indicated a positive correlation between these errors (Pearson's correlation coefficient r=0.795, p-value=7.04 × 10⁻¹⁵), RE being about twice ICE. The ICEs averaged 1.5 mm and 2.5 mm in the duodenum and stomach. For the duodenum, cumulative D0.03cc and D1cc at the end of treatment ranged from 85.7% to 100.4% of the plan constraint value (confidence intervals included). The uncertainty intervals were between 1.1% and 2.2% in four cases and approximately 7% for the fifth case. Cumulative D0.03cc in the stomach varied from 89.4% to 102.8%, with uncertainty intervals that extended from 2.5% to 6.4%. All Dmax lower limits were below 100%. <h3>Conclusion</h3> Voxel-wise uncertainties in DIR-based dose accumulation during MRgART of abdominal cancer can be estimated using an ICE-based technique. The derived confidence intervals for cumulative Dmax (D1cc or D0.03cc) of OARs (the duodenum and stomach) can be utilized to guide daily dose adaptation throughout MRgART.

Synthetic CT generation for MRI-guided adaptive radiotherapy in prostate cancer.

Current MRI-guided adaptive radiotherapy (MRgART) workflows require fraction-specific electron and/or mass density maps, which are created by deformable image registration (DIR) between the simulation CT images and daily MR images. Manual density overrides may also be needed where DIR-produced results are inaccurate. This approach slows the adaptive radiotherapy workflow and introduces additional dosimetric uncertainties, especially in the presence of the magnetic field. This study investigated a method based on a conditional generative adversarial network (cGAN) with a multi-planar method to generate synthetic CT images from low-field MR images to improve efficiency in MRgART workflows for prostate cancer. Fifty-seven male patients, who received MRI-guided radiation therapy to the pelvis using the ViewRay MRIdian Linac, were selected. Forty-five cases were randomly assigned to the training cohort with the remaining twelve cases assigned to the validation/testing cohort. All patient datasets had a semi-paired DIR-deformed CT-sim image and 0.35T MR image acquired using a true fast imaging with steady-state precession (TrueFISP) sequence. Synthetic CT images were compared with deformed CT images to evaluate image quality and dosimetric accuracy. To evaluate the dosimetric accuracy of this method, clinical plans were recalculated on synthetic CT images in the MRIdian treatment planning system. Dose volume histograms for planning target volumes (PTVs) and organs-at-risk (OARs) and dose distributions using gamma analyses were evaluated. The mean-absolute-errors (MAEs) in CT numbers were 30.1 ± 4.2 HU, 19.6 ± 2.3 HU and 158.5 ± 26.0 HU for the whole pelvis, soft tissue, and bone, respectively. The peak signal-to-noise ratio was 35.2 ± 1.7 and the structural index similarity measure was 0.9758 ± 0.0035. The dosimetric difference was on average less than 1% for all PTV and OAR metrics. Plans showed good agreement with gamma pass rates of 99% and 99.9% for 1%/1 mm and 2%/2 mm, respectively. Our study demonstrates the potential of using synthetic CT images created with a multi-planar cGAN method from 0.35T MRI TrueFISP images for the MRgART treatment of prostate radiotherapy. Future work will validate the method in a large cohort of patients and investigate the limitations of the method in the adaptive workflow.

MRI-guided adaptive radiotherapy for prostate cancer: When do we need to account for intra-fraction motion?

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate.

Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]: A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy

IntroductionRadiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. MethodsThe PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues.The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. DiscussionThe PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk.Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021.Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021.

Interobserver variability in target volume delineation for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer.

Objectives:Quantify target volume delineation uncertainty for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer. Define optimal imaging sequences for target delineation.Methods:Six experienced radiation oncologists delineated clinical target volumes (CTVs) on CT and 2D and 3D-MRI in three patients with rectal cancer, using consensus contouring guidelines. Tumour GTV (GTVp) was also contoured on MRI acquired week 0 and 3 of radiotherapy. A STAPLE contour was created and volume and interobserver variability metrics were analysed.Results:There were statistically significant differences in volume between observers for CT and 2D-MRI-defined CTVs (p < 0.05). There was no significant difference between observers on 3D-MRI. Significant differences in volume were seen between observers for both 2D and 3D-MRI-defined GTVp at weeks 0 and 3 (p < 0.05). Good interobserver agreement (IOA) was seen for CTVs delineated on all imaging modalities with best IOA on 3D-MRI; median Conformity index (CI) 0.74 for CT, 0.75 for 2D-MRI and 0.77 for 3D-MRI. IOA of MRI-defined GTVp week 0 was better compared to CT; CI 0.58 for CT, 0.62 for 2D-MRI and 0.7 for 3D-MRI. MRI-defined GTVp IOA week three was worse compared to week 0.Conclusion:Delineation on MRI results in smaller volumes and better IOA week 0 compared to CT. 3D-MRI provides the best IOA in CTV and GTVp. MRI-defined GTVp on images acquired week 3 showed worse IOA compared to week 0. This highlights the need for consensus guidelines in GTVp delineation on MRI during treatment course in the context of dose escalation MRI-guided rectal boost studies.Advances in knowledge:Optimal MRI sequences for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer have been defined.

Should Daily Online Adaptive Replanning be Utilized for Every Treatment in MRI-Guided Radiotherapy for Pancreatic Cancer?

<h3>Purpose/Objective(s)</h3> Linear accelerators with onboard MRI caused a paradigm shift in radiotherapy by allowing for daily online MRI guided adaptive radiotherapy (MRgART). Customized plans can be generated and delivered using the acquired daily images while the patient is on the treatment table. However, online adaptive radiotherapy re-planning (OLAR) is labor intensive and time consuming. In this study, we investigate whether adapting the radiotherapy plan daily, accounting for interfractional organ motion, is necessary for every fraction during hypofractionated RT for pancreatic cancer. <h3>Materials/Methods</h3> Data from 70 fractions collected for pancreatic cancer patients treated with 30-35 Gy in 5 fractions using OLAR on a 1.5T MR-Linac were analyzed. For each daily MRI scan, a reposition (non-adaptive) plan was generated by re-calculating the initial undelivered reference plan based on the daily anatomy via rigid registration of the planning and daily images. The daily images were re-contoured during the OLAR process. Data for the non-adaptive plans was analyzed using the daily contours. The daily OLAR and non-adaptive plans were then compared to determine whether the non-adaptive plans would have been clinically acceptable and equivalent to the OLAR plan quality. Plan quality was defined by first prioritizing the dose constraints of the organs at risk (OAR) and second by the planning target volume (PTV) coverage. Statistical significance was determined by using a one-tailed t-test (<i>p</i> < 0.05). <h3>Results</h3> Dose constraints for the kidneys, spinal cord, liver, and skin were met for all OLAR and non-adaptive plans. For the OLAR plans, only 5.7% and 8.6% did not meet duodenum and small bowel dose constrains, respectively. For the non-adaptive plans, 45.7%, 5.7%, 28.6%, and 11.4% did not meet duodenum, small bowel, stomach, and colon dose constraints, respectively. The dose difference (17.5-1050 cGy) beyond what's clinically acceptable for the duodenum was the most statistically significant (<i>p</i> < 0.05). In addition, 32 OLAR plans and 12 non-adaptive plans met all planning objectives. From the 12 criteria-met non-adaptive plans, 4 had a significant (<i>p</i> < 0.05) increase in PTV coverage over the OLAR plans. Among all the 70 fractions, the non-adaptive plans were equivalent to the OLAR plans in 25 fractions (36%), i.e., OLAR was necessary in 45 treatment fractions (64%) (<i>p</i> < 0.05). <h3>Conclusion</h3> OLAR can significantly reduce GI OAR dose leading to an improvement in delivered plan quality in MRgART for pancreatic cancer. This study shows that the plan quality differences between the OLAR and non-adaptive plans justify the use of daily online adaptive re-planning for the majority (64%) of the treatments. To increase OLAR efficiency, a focus in online contouring and contour evaluation primarily on GI OAR structures may be warranted. With more automation for OLAR process being developed, the argument for not using OLAR for every fraction may become obsolete.