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Purpose: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium., Methods and Materials: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment)., Results: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed., Conclusions: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging., (Copyright © 2021. Published by Elsevier Inc.)

Background and purpose: In this study we developed a workflow for fully-automated generation of deliverable IMRT plans for a 1.5 T MR-Linac (MRL) based on contoured CT scans, and we evaluated automated MRL planning for rectal cancer. Methods: The Monte Carlo dose calculation engine used in the clinical MRL TPS (Monaco, Elekta AB, Stockholm, Sweden), suited for high accuracy dose calculations in a 1.5 T magnetic field, was coupled to our in-house developed Erasmus-iCycle optimizer. Clinically deliverable plans for 23 rectal cancer patients were automatically generated in a two-step process, i.e., multi-criterial fluence map optimization with Erasmus-iCycle followed by a conversion into a deliverable IMRT plan in the clinical TPS. Automatically generated plans (AUTOplans) were compared to plans that were manually generated with the clinical TPS (MANplans). Results: With AUTOplanning large reductions in planning time and workload were obtained; 4-6 h mainly hands-on planning for MANplans vs ∼1 h of mainly computer computation time for AUTOplans. For equal target coverage, the bladder and bowel bag D mean was reduced in the AUTOplans by 1.3 Gy (6.9%) on average with a maximum reduction of 4.5 Gy (23.8%). Dosimetric measurements at the MRL demonstrated clinically acceptable delivery accuracy for the AUTOplans. Conclusions: A system for fully automated multi-criterial planning for a 1.5 T MR-Linac was developed and tested for rectal cancer patients. Automated planning resulted in major reductions in planning workload and time, while plan quality improved. Negative impact of the high magnetic field on the dose distributions could be avoided.

Background: The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer., Methods: Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary., Results: All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers., Conclusions: Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning., Trial Registration: The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

Background and Purpose: A GTV boost is suggested to result in higher complete response rates in rectal cancer patients, which is attractive for organ preservation. Fiducials may offer GTV position verification on (CB)CT, if the fiducial-GTV spatial relationship can be accurately defined on MRI. The study aim was to evaluate the MRI visibility of fiducials inserted in the rectum., Materials and Methods: We tested four fiducial types (two Visicoil types, Cook and Gold Anchor), inserted in five patients each. Four observers identified fiducial locations on two MRI exams per patient in two scenarios: without (scenario A) and with (scenario B) (CB)CT available. A fiducial was defined to be consistently identified if 3 out of 4 observers labeled that fiducial at the same position on MRI. Fiducial visibility was scored on an axial and sagittal T2-TSE sequence and a T1 3D GRE sequence., Results: Fiducial identification was poor in scenario A for all fiducial types. The Visicoil 0.75 and Gold Anchor were the most consistently identified fiducials in scenario B with 7 out of 9 and 8 out of 11 consistently identified fiducials in the first MRI exam and 2 out of 7 and 5 out of 10 in the second MRI exam, respectively. The consistently identified Visicoil 0.75 and Gold Anchor fiducials were best visible on the T1 3D GRE sequence., Conclusion: The Visicoil 0.75 and Gold Anchor fiducials were the most visible fiducials on MRI as they were most consistently identified. The use of a registered (CB)CT and a T1 3D GRE MRI sequence is recommended., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Day-to-day shape variation in the rectum CTV results in considerable geometric uncertainties during rectal cancer radiotherapy. To ensure coverage a large CTV-to-PTV margin is required. The purpose of this study was to increase the accuracy of treatment delivery by building a population based library of planning CTVs for rectal cancer patients and to evaluate its potential for rectum PTV margin and PTV volume reduction., Methods: Analysis was done retrospectively on 33 early-stage rectal cancer patients with daily repeat CTs who received short-course pre-operative radiotherapy in 5 fractions of 5 Gy. We created signed distance maps from the planning rectum CTV to each of the repeat CTVs, from which we calculated the group mean, systematic and random error. The correlation between different regions of the rectum CTV was analyzed and used in combination with the distance maps to create the library of nine planning CTVs. For each of the repeat CTVs the best fitting CTV structure in the library was automatically selected defined by the plan that minimized the mean absolute distance between the repeat and library CTV. Residual distance maps were calculated from which a new PTV margin was constructed. Bootstrapping was performed on the margin difference to assess its significance., Results: Residual errors were found to decrease with the number of plans in the library, but adding more than five plans yields negligible further error reduction. Margin reduction of up to 50% was achieved at the upper-anterior site of the mesorectum. The average PTV volume decreased by 15.5% when a library is introduced., Conclusions: A library of plans strategy for rectal cancer based on population statistics is feasible and results in a considerably reduced average rectum PTV volume compared to conventional radiotherapy., (© 2018 American Association of Physicists in Medicine.)

Purpose: MRI guidance during radiotherapy has the potential to enable more accurate dose delivery, optimizing the balance between local control and treatment related toxicity. However, the presence of a permanent magnetic field influences the dose delivery, especially around air cavities. Here, electrons are able to return to the surface through which they entered the air cavity (electron return effect, ERE) locally resulting in dose hot- and cold-spots. Where RT of rectal cancer patients might benefit from MRI guidance for margin reduction, air cavities in and around the target volume are frequently present. The purpose of this research is to evaluate the impact of the presence of a 1.5 T transverse magnetic field on dose delivery in patients with rectal cancer., Methods: Ten patients treated with 5 × 5 Gy RT having large changes in pelvic air content were selected out of a cohort of 33 patients. On the planning CT, a 1.5 T, 6 MV, 7-field intensity modulated radiotherapy (IMRT) plan was created. This plan was subsequently recalculated on daily CT scans. For each daily CT, the CTV V95% and V107% and bowel area V(5Gy), V(10Gy), V(15Gy), V(20Gy), and V(25Gy) were calculated to evaluate the changes in dose distribution from fraction to fraction. For comparison, the authors repeated this procedure for the 0 T situation. To study the effect of changing air cavities separate from other anatomical changes, the authors also generated artificial air cavities in the CTV of one patient (2 and 5 cm diameter), in the high dose gradient region (2 cm), and in the low dose area (2 cm). Treatment plans were optimized without and with each simulated air cavity. For appearing and disappearing air cavities, the CTV V95% and V107% were evaluated. The authors also evaluated the ERE separate from attenuation changes locally around appearing gas pockets., Results: For the ten patients, at 1.5 T, the V95% was influenced by both appearing and disappearing air, and dropped to <98% in 2 out of 50 fractions due a disappearing air cavity of 150 cm(3). V95% differences between 0 and 1.5 T were all within 2%. The V107% was below 1% in 46 out of 50 fractions, and increased to 3% in the remaining fractions due to appearing air of around 120 cm(3). For comparison, V107% was <1% at 0 T for all fractions. In the bowel area, the V15Gy varied strongest from fraction to fraction, but differences between 1.5 and 0 T were minimal with an average difference of 2.3 cm(3) (SD = 18.7 cm(3), p = 0.38). For the simulated air cavities, the ERE resulted in cold-spots maximally 5% lower than prescribed and hot-spots maximally 6% higher than prescribed., Conclusions: The presence of a 1.5 T magnetic field has an impact on the dose distribution when the air content changes of within a few percent in these selected rectal cancer patients. The authors consider this influence of the transverse magnetic field on the dose distribution in IMRT for rectal cancer patients clinically acceptable.

Purpose: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction., Methods and Materials: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry., Results: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed., Conclusions: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Hydrogel injected between the rectum and prostate prior to radiotherapy provides a possible means of increased dose sparing to the rectum. Here the authors evaluate the overlap volume histogram (OVH) metric as a means to predict the rectal dose following hydrogel injection. Whether OVH predicted dose can serve as the dose objective or constraint for automated treatment planning was also investigated., Methods: Treatment planning was performed on 21 prostate cancer patients both pre- and posthydrogel injection, with five-field IMRT delivering 78 Gy to the planning target volume (PTV). The authors quantify the geometrical relationship between the rectum and the prostate PTV using an OVH metric which determines the fractional volume of the rectum that is within a specified distance of the PTV. For an OVH distance the authors selected, L(20), the PTV expansion distance at which 20% of the rectum overlaps. The authors calculated the rectal dose, D(20), received by 20% of the rectum volume on the dose volume histogram. Linear regression was used to examine the correlation between the L(20) and D(20), and between ΔL(20) and ΔD(20) (i.e., the change of L(20) and D(20) posthydrogel injection). Additionally, rectal dose D(15), D(25), D(35), D(50), and bladder dose D(15) were predicted from the OVH (L(15), L(25), L(35), L(50), for rectum and L(15) for bladder) by the L(x)-D(x) linear regression. The predicted doses were applied to the objectives for automated treatment planning of ten plans from five patients. Automatically generated plans were compared with plans manually generated on trial-and-error basis., Results: The rectal L(20) was increased and dose D(20) decreased due to the enlarged separation of rectum caused by the hydrogel injection. Linear regression showed an inverse linear correlation between L(20) and D(20), and between ΔL(20) and ΔD(20) (r(2) = 0.77, 0.60, respectively; p < 0.0001). The increase in rectal sparing (ΔD(20)) is only weakly correlated with the volume of injected hydrogel (r(2) = 0.17; p = 0.07), indicating OVH is a more predictive indicator of rectal sparing than the volume of hydrogel itself. Application of the predicted rectum and bladder doses to automated planning produced acceptable treatment plans, with rectal dose reduced for eight of ten plans., Conclusions: The OVH metric can predict the rectal dose in the external beam prostate radiotherapy for patients with hydrogel injection. The predicted doses can be applied to the objectives of optimization in automated treatment planning to produce acceptable treatment plans.

Purpose: To quantify the potential margin reduction with adaptive radiotherapy (ART) during neo-adjuvant treatment of locally-advanced rectal cancer., Methods and Materials: Repeat CT scans were acquired for 28 patients treated with 25×2 Gy, daily during the first week, and followed by weekly scans. The CTV was delineated on all scans, and shape variation was estimated. Five ART strategies were tested, consisting of an average CTV over the planning CT and one to five repeat CTs. Required PTV margins were calculated for adapted and non-adapted treatment. The strategy with the least PTV volume over the whole treatment was selected and bowel area dose reduction was estimated., Results: Substantial systematic and random shape variation demanded for a PTV margin up to 2.4 cm at the upper-anterior part of the CTV. Plan adaptation after fraction 4 resulted in a maximum 0.7 cm margin reduction and a significant PTV reduction from 1185 to 1023 cc (p<0.0001). The bowel area volume receiving 15, 45, and 50 Gy was reduced from 436 to 402 cc, 111 to 81 cc, and 49 to 29 cc, respectively (p<0.0001)., Conclusions: With adaptive radiotherapy, maximum required PTV margins can be reduced from 2.4 to 1.7 cm, resulting in significantly less dose to the bowel area., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To quantify the inter-fraction shape variation of the CTV in rectal-cancer patients treated with 5 × 5 (SCRT) and 25 × 2 Gy (LCRT) and derive PTV margins., Methods and Materials: Thirty-three SCRT with daily repeat CT scans and 30 LCRT patients with daily scans during the first week followed by weekly scans were included. The CTV was delineated on all scans and local shape variation was calculated with respect to the planning CT. Margin estimation was done using the local shape variation to assure 95% minimum dose for at least 90% of patients., Results: Using 482 CT scans, systematic and random CTV shape variation was heterogeneous, ranging from 0.2 cm close to bony structures up to 1.0 cm SD at the upper-anterior CTV region. A significant reduction in rectal volume during LCRT resulted in an average 0.5 cm posterior shift of the upper-anterior CTV. Required margins ranged from 0.7 cm close to bony structures up to 3.1 and 2.3 cm in the upper-anterior region for SCRT and LCRT, respectively., Conclusions: Heterogeneous shape variation demands anisotropic PTV margins. Required margins were substantially larger in the anterior direction compared to current clinical margins. These larger margins were, however, based on strict delineated CTVs, resulting in smaller PTVs compared to current practice., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)