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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 MRLinac 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. (c) 2021 Published by Elsevier Inc.

We present the first case in the literature of a patient with a histology-proven intimal sarcoma of the heart, recurrent after surgery, treated with stereotactic MR-guided online adaptive radiation therapy on an MR-Linac machine. The treatment was feasible and well tolerated. The CT scan 6 months after the last treatment showed stable disease.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Purpose The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging—guided brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles. Methods and Materials This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS clinical ) with an additionally generated optimized plan without needle use (IC study ). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV). Results A total of 54 needles (range, 1–6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4–35%) and 7% (range, 2–14%) of the implant treatment time, respectively. The total (external-beam radiotherapy + brachytherapy) D90 HR-CTV for the IC study and the IC/IS clinical were on average 79.5 (SD 7.4) Gy α/β10 and 83.9 (SD 6.7) Gy α/β10 , respectively, with an average gain of 4.4 (SD 2.3) Gy α/β10 for the second application. Conclusions Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us deeper understanding of the possibilities in magnetic resonance imaging—guided (pre)treatment planning with the IC/IS Utrecht applicator.

Purpose The aim of this study was to determine the changes in the excision cavity volume due to the resolution of the surgical effects during the whole breast treatment. Materials and Methods Seventy-seven patients with early-stage (T1-2 N0) breast cancer treated with breast-conserving therapy were included for this study. All patients underwent a standard planning computed tomography (CT) scan before irradiation treatment. A second CT scan was performed in the week before the start of the boost. Excision cavity volumes were delineated based on the surgical clips and the (surrounding) seroma or hematoma or other surgical changes on both scans by an experienced physician. This resulted in the gross tumor volumes GTV1 and GTV2. Results The delineated volumes of the GTVs were on average 78.7 cm 3 (range, 1.1–236.0 cm 3 ) and 29.7 cm 3 (range, 1.3–123.6 cm 3 ) for, respectively, GTV1 and GTV2. The time between the CT scans was on average 37 days (range, 29–74 days). This resulted in a reduction of on average 62%. The absolute reduction per day of the GTV1 was –1.3 cm 3 /day (range, 0.3 to –5.4 cm 3 /day). A linear correlation (correlation coefficient r 2 = 0.81) was observed between the absolute volume of GTV1 and the absolute reduction per day. Conclusion A significant reduction in excision cavity volume during whole breast irradiation was shown. The observed correlation might be helpful in the decision to perform a second CT scan to adapt the treatment plan.

For breast boost radiotherapy or accelerated partial breast irradiation, the tumor bed (TB) is delineated by the radiation oncologist on a planning computed tomography (CT) scan. The aim of the present study was to investigate whether the interobserver variability (IOV) of the TB delineation is reduced by providing the radiation oncologist with additional magnetic resonance imaging (MRI) or CT scans. A total of 14 T1-T2 breast cancer patients underwent a standard planning CT in the supine treatment position following lumpectomy, as well as additional pre-and postoperative imaging in the same position. Post-lumpectomy TBs were independently delineated by four breast radiation oncologists on standard postoperative CT and on CT registered to an additional imaging modality. The additional imaging modalities used were postoperative MRI, preoperative contrast-enhanced (CE)-CT and preoperative CE-MRI. A cavity visualization score (CVS) was assigned to each standard postoperative CT by each observer. In addition, the conformity index (CI), volume and distance between centers of mass (dCOM) of the TB delineations were calculated. On CT, the median CI was 0.57, with a median volume of 22 cm3 and dCOM of 5.1 mm. The addition of postoperative MRI increased the median TB volume significantly to 28 cm3 (P3, respectively (both P

Background and purpose To determine the interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation. Patients and methods Eighteen consecutive patients with left sided breast cancer treated by breast conserving surgery agreed to participate in our study. Volumes of the glandular breast tissue (CTV breast) and of the boost (CTV boost) were delineated by five observers. We determined ‘conformity indices’ (CI) and the ratio between the volume of each CTV and the mean volume of all CTVs (CTV ratio). Subsequently we determined the most medial, lateral, anterior, posterior, cranial and caudal extensions both of CTV breast and CTV boost for all observers separately. Results The mean CI breast was 0.87. For one observer we noted the highest CTV ratio in 17 out of 18 cases. No association was noted between CI breast and menopausal status. The mean CI boost was 0.56. We did not find a relation between the presence or absence of clips and the CI boost. For another observer we noted the lowest CTV boost ratio in 10 out of 17 cases. Conclusions We recommend that each institute should determine its interobserver variability with respect to CTV breast and CTV boost before implementing the delineation of target volumes by planning CT in daily practice.

PURPOSE: To affirm the effectiveness and complication rate of postoperative single-dose beta-irradiation (RT) with (90)Sr in the case of primary pterygium in a clinical trial. Pterygium is a benign disease of the supporting orbital tissue that can cause impairment of visual function. Depending on the technique used for surgery, recurrence is described in up to 70% of cases-a reason to combine the initial treatment with radiotherapy or chemotherapy. METHODS AND MATERIALS: This trial was designed as a prospective, randomized, multicenter, double-blind study. Surgery was performed in all cases according to the bare sclera technique. Ninety-one patients with 96 pterygia were postoperatively randomized to either beta-RT or sham RT. In the case of beta-RT, a (90)Sr eye applicator was used to deliver 2500 cGy to the sclera surface at a dose rate of between 200 and 250 cGy/min. Sham RT was given using the same type of applicator without the (90)Sr layer. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. RESULTS: Between February 1998 and September 2002, 96 eyes with primary pterygium were operated on according to the trial protocol. Additional treatment was performed within 24 hours postoperatively. Ten patients were lost to follow-up, resulting in 86 patients who could be analyzed. In the 44 eyes randomized to receive beta-RT, 3 relapses occurred compared with 28 recurrences in the 42 eyes that received sham RT, for a crude control rate of 93.2% vs. 33.3%, respectively. At a mean follow-up of 18 months, major treatment complications had not been observed. CONCLUSION: Single-dose beta-RT after bare sclera surgery is a simple, effective, and safe treatment that reduces the risk of primary pterygium recurrence

Dosimetric intra-fraction uncertainties in MRI-guided brachytherapy were analysed for HR-CTV and OARs. While dose differences were generally small, individual outliers occurred. In contrast to HDR, patients treated with PDR show increased mean rectal dose over time. Re-imaging prior to dose delivery helps to detect unfavorable anatomical changes, and allows for intervention.

Background: Accurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy.Methods: Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), center of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist.Results: Preoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p < 0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p = 0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range 30-153 cm3) on MRI (p < 0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI.Conclusions: This study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy.Trial registration: International Clinical Trials Registry Platform NTR3198. © 2014 den Hartogh et al.; licensee BioMed Central Ltd.

Contains fulltext : 118155.pdf (Publisher’s version ) (Closed access) PURPOSE: To evaluate dosimetric parameters and clinical outcome for cervical cancer patients treated with chemo-radiation and MR-image guided adaptive brachytherapy (MR-IGABT) using tandem-ovoid applicators for intracavitary or combined intracavitary/interstitial approaches. METHOD: This retrospective analysis includes 46 patients treated between 2006 and 2008. Dose-volume parameters D90 HR-CTV (high-risk clinical target volume) and D2cc OARs (organs at risk) were determined and converted into biologically equivalent doses in 2Gy fractions (EQD2). Clinical outcome parameters (local control (LC), progression free survival (PFS) and overall survival (OS)) were analysed actuarially and late morbidity crude rates were scored using CTCAEv3.0. RESULTS: Mean D90 HR-CTV was 84 (SD9) Gy EQD2 for HR-CTV volumes of mean 57 (SD37) cm(3) at time of first brachytherapy (BT). Median follow-up was 41 (range, 4-67)months. Three year LC, PFS, and OS rates were 93, 71, and 65%, respectively. Node negative patients had significantly higher 3-year survival rates compared to node positive ones (PFS 85 versus 53% (p=0.013), OS 77 versus 50% (p=0.032), respectively) with an even larger difference for patients with FIGO stages IB-IIB (PFS 87 versus 42% (p=0.002), OS 83 versus 46% (p=0.007), respectively). Late grade 3-4 mainly gastrointestinal or vaginal morbidity was observed in 4 patients (9.5%). No correlations were seen between morbidity and D2cc OAR values. CONCLUSION: (Chemo-) radiation and MR-IGABT with tandem-ovoid applicators result in high LC and promising survival rates with reasonable morbidity. 01 april 2013

Background and purpose The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV–PTV margins. We also studied their correlation with surrounding organ filling. Materials and methods Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage. Results The vaginal CTVs change their position in the pelvis during time with a maximum in anterior–posterior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV–PTV margin ⩾5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior–posterior. Conclusion To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior–posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder.

Purpose To study the impact of MRI-guided treatment planning on dose/volume parameters in pulsed dose rate (PDR) brachytherapy (BT) for cervical cancer. Additionally, we investigated the potential benefit of an intracavitary/interstitial (IC/IS) modification of the classical tandem ovoid applicator. Material and methods For 24 patients we compared Standard PDR BT plans, Scaled Standard plans and MRI-guided Optimised plans. The total EBRT/BT prescribed dose to Manchester point A or to 90% of the HR-CTV (D90 HR-CTV) [1] expressed in EQD 2 was 80 Gy αβ10 in 17 patients (Period I) and 84 Gy αβ10 in 7 patients (Period II). The constraints to 2 cm 3 of the OAR were 90 Gy αβ3 for bladder and 75 Gy αβ3 for rectum, sigmoid and bowel. Most cases were treated with a traditional intracavitary tandem ovoid applicator. In 6 patients we used a newly designed combined IC/IS modification for the second PDR fraction and investigated the benefit of the interstitial part. Results The average gain of MRI-guided optimisation expressed in D90 HR-CTV was 4 ± 9 Gy αβ10 ( p αβ10 ( p = 0.003) in the two periods. The dose to 2 cm 3 of the OAR met the constraints. In the group that was treated with the combined IC/IS approach, we could increase the D90 HR-CTV for the second PDR fraction with 5.4 ± 4.2 Gy αβ10 ( p = 0.005) and the D100 with 4.8 ± 3.1 Gy αβ10 ( p = 0.07). Conclusions Three-dimensional MRI-guided treatment planning and optimisation improves the DVH parameters compared to conventional planning strategies. Additional improvement can be achieved by using a combined IC/IS approach.

Background and Purpose For cervical cancer patients the CTV consists of multiple structures, exhibiting complex inter-fraction changes. The purpose of this study is to use weekly MR imaging to derive PTV margins that accommodate these changes. Materials and methods Twenty patients with cervical cancer underwent a T2-weighted MRI exam before and weekly during IMRT. The CTV, GTV and surrounding organs were delineated. PTV margins were derived from the boundaries of the GTV and CTV in the six main directions and correlated with changes in the volumes of organs at risk. Results Around the GTV a margin of 12, 14, 12, 11, 4 and 8 mm to the anterior, posterior, right lateral, left lateral, superior and inferior directions was needed. The CTV required margins of 24, 17, 12, 16, 11 and 8 mm. The shift of the GTV and CTV in the AP directions correlated weakly with the change in rectal volume. For the bladder the correlations were even weaker. Conclusions We used weekly MRI scans to derive inhomogeneous PTV margins that accommodate changes in GTV and CTV. The weak correlations with rectum and bladder volume suggest that measures to control filling status of these organs may not be very effective.

Background and Purpose: For cervical cancer patients the CTV consists of multiple structures, exhibiting complex inter-fraction changes. The purpose of this study is to use weekly MR imaging to derive PTV margins that accommodate these changes. Materials and methods: Twenty patients with cervical cancer underwent a T2-weighted MRI exam before and weekly during IMRT. The CTV, GTV and surrounding organs were delineated. PTV margins were derived from the boundaries of the GTV and CTV in the six main directions and correlated with changes in the volumes of organs at risk. Results: Around the GTV a margin of 12, 14, 12, 11, 4 and 8 mm to the anterior, posterior, right lateral, left lateral, superior and inferior directions was needed. The CTV required margins of 24, 17, 12, 16, 11 and 8 mm. The shift of the GTV and CTV in the AP directions correlated weakly with the change in rectal volume. For the bladder the correlations were even weaker. Conclusions: We used weekly MRI scans to derive inhomogeneous PTV margins that accommodate changes in GTV and CTV. The weak correlations with rectum and bladder volume suggest that measures to control filling status of these organs may not be very effective. c 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 88 (2008) 233–240.