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Background Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT. Materials and methods Ninety patients with metachronous oligometastatic prostate cancer received SBRT for 1-3 lymph node metastases diagnosed on 68Ga-PSMA-PET/CT. The primary end point was progression free survival (PFS), with disease progression defined as occurrence of either target lesion progression, new metastatic lesion or biochemical progression. Secondary outcomes were biochemical PFS (BPFS), ADT-free survival (ADT-FS), toxicity and quality of life (QoL). Baseline patient characteristics were tested for association with PFS and a preliminary risk score was created. Results Median follow-up was 21 months (interquartile range 10-31 months). Median PFS and BPFS were 16 and 21 months, respectively. Median ADT-FS was not reached (73% (95%-CI 62-86%) at 24 months). In multivariable analysis, younger age, higher PSA prior to SBRT and extrapelvic location were associated with shorter PFS. Grade 1 fatigue was the most predominant acute toxicity (34%). Highest grade toxicity was grade 2 for acute and late events. QoL analysis showed mild, transient increase in fatigue at 1-4 weeks after SBRT. Conclusion A median PFS of 16 months was attained after SBRT for patients with PSMA-PET positive oligometastatic lymph nodes from prostate cancer. Higher pre-SBRT PSA, younger age and extrapelvic location were found to be predictors of shorter PFS.

BACKGROUND AND PURPOSE The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules. METHODS 27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n = 26 cranial, n = 24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2α/β=10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20 fractions, V95% ≥ 99%, D0.1cm3 ≤ 107%) and hypofractionated (15/10/5/3 fractions, V100% ≥ 95%, D0.1cm3 ≤ 120%). Relative EQD2 differences in OARs Dmean between the different schedules were compared. RESULTS PTV coverage was met for all plans independently of the fractionation schedule and for all lesions (V95% range 95.5-100%, V100% range 95.1-100%), with exception of the vertebrae (V100% range 63.5-91.0%). For most OARs, relative mean reduction in the Dmean was seen for the hypofractionated plans compared to the conventional plans, with largest sparing in the 5 fractions (< 43%) followed by the 3 fractions schedule (< 40%). In case of PTV overlap with an OAR, a significant increase in dose for the OAR was observed with hypofractionation. CONCLUSIONS For the majority of the cases, iso-effective plans with hypofractionation were feasible with similar or less dose in the OARs. The most suitable fractionation schedule should be personalised depending on the spatial relationship between the PTV and OARs and the prescription dose.

Purpose At our department, MR-guided stereotactic body radiation therapy (SBRT) using the 1.5T MR-linac system (Unity, Elekta AB, Stockholm, Sweden) has been initiated for patients with lymph node oligometastases. Superior soft tissue contrast and the possibility for online plan adaptation on the Unity may allow for hypofractionated treatment. The purpose of this study was to investigate the dosimetric feasibility and compare the plan quality of different hypofractionated schemes. Methods and materials Data was used from 12 patients with single lymph node oligometastases (10 pelvic, 2 para-aortic), which were all treated on the Unity with a prescribed dose of 5x7 Gy to 95% of the PTV. Hypofractionation was investigated for 3x10 Gy and 1x20 Gy schemes (all 60 Gy BED α/β = 10). The pre-treatment plans were evaluated based on dose criteria and plan quality. If all criteria were met, the number of online adapted plans which also met all dose criteria was investigated. For pre-treatment plans meeting the criteria for all three fractionation schemes, the plan quality after online adaptation was compared using the four parameters described in the NRG-BR001 phase 1 trial. Results Pre-treatment plans met all clinical criteria for the three different fractionation schemes in 10, 9 and 6 cases. 50/50, 45/45 17/30 of the corresponding online adapted plans met all criteria, respectively. Violations were primarily caused by surrounding organs at risk overlapping or adjacent to the PTV. The 1x20 Gy treatment plans were, in general, of lesser quality than the 5x7 Gy and 3x10 Gy plans. Conclusion Hypofractionated radiotherapy for lymph node oligometastases on the 1.5T MR-linac is feasible based on dose criteria and plan quality metrics. The location of the target relative to critical structures should be considered in choosing the most suitable fractionation scheme. Especially for single fraction treatment, meeting all dose criteria in the pre-treatment situation does not guarantee that this also applies during online treatment.

Background and purpose Patients were treated at our institute for single and multiple lymph node oligometastases on the 1.5T MR-linac since August 2018. The superior soft-tissue contrast and additional software features of the MR-linac compared to CBCT-linacs allow for online adaptive treatment planning. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with conventional CBCT-linac treatment. Materials and methods Patient data was used from 14 patients with single lymph node oligometastases and 6 patients with multiple (2–3) metastases. All patients were treated on the 1.5T MR-linac with a prescribed dose of 5 × 7 Gy to 95% of the PTV and a CBCT-linac plan was created for each patient. The difference in target coverage between these plans was compared and plans were evaluated based on dose criteria for each fraction after calculating the CBCT-plan on the daily anatomy. The GTV coverage was evaluated based on the online planning and the post-delivery MRI. Results For both single and multiple lymph node oligometastases the GTV V35Gy had a median value of 100% for both the MR-linac plans and CBCT-plans pre- and post-delivery and did not significantly differ. The percentage of plans that met all dose constraints was improved from 19% to 84% and 20% to 67% for single and multiple lymph node cases, respectively. Conclusion Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment shows a smaller amount of unplanned violations of high dose criteria. The GTV coverage was comparable. Benefit is primarily gained in patients treated for multiple lymph node oligometastases: geometrical deformations are accounted for, dose can be delivered in one plan and margins can be reduced.

BACKGROUND AND PURPOSE Vacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion. MATERIALS AND METHODS Thirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction. RESULTS Vacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

Background. In radiotherapy, the magnitude of respiratory-induced tumor motion is often measured using a single four-dimensional computed tomography (4DCT). This magnitude is required to determine the internal target volume. The aim of this study was to compare the magnitude of respiratory-induced motion of pancreatic tumors on a single 4DCT with the motion on daily cone beam CT (CBCT) scans during a 3–5-week fractionated radiotherapy scheme. In addition, we investigated changes in the respiratory motion during the treatment course.Material and methods. The mean peak-to-peak motion (i.e. magnitude of motion) of pancreatic tumors was measured for 18 patients using intratumoral gold fiducials visible on CBCT scans made prior to each treatment fraction (10–27 CBCTs per patient; 401 CBCTs in total). For each patient, these magnitudes were compared to the magnitude measured on 4DCT. Possible time trends were investigated by applying linear fits to the tumor motion determined from daily CBCTs as a function of treatment day.Results. We found a significant (p ≤ 0.01) difference between motion magnitude on 4DCT and on CBCT in superior-inferior, anterior-posterior and left-right direction, in 13, 9 and 12 of 18 patients, respectively. In the anterior- posterior and left-right direction no fractions had a difference ≥ 5 mm. In the superior-inferior direction the difference was ≥ 5 mm for 17% of the 401 fractions. In this direction, a significant (p ≤ 0.05) time trend in tumor motion was observed in 4 of 18 patients, but all trends were small (− 0.17–0.10 mm/day) and did not explain the large differences in motion magnitude between 4DCT and CBCT.Conclusion. A single measurement of the respiratory-induced motion magnitude of pancreatic tumors using 4DCT is often not representative for the magnitude during daily treatment over a 3–5-week radiotherapy scheme. For this patient group it may be beneficial to introduce breath-hold to eliminate respiratory-induced tumor motion.

PURPOSE: Online 1.5T MR imaging on the MR-linac gives better target visualization compared to CBCT and facilitates online adaptive treatment strategies including daily replanning. In this simulation study, the dosimetric impact of online replanning was investigated for SBRT of lymph node oligometastases as a method for correcting for inter-fraction anatomical changes. METHODS: Pre-treatment plans were created for 17 pelvic and para-aortic lymph nodes, with 3 and 8 mm PTV margins reflecting our clinical practice for lymph nodes with good and poor visibility on CBCT. The dose-volume parameters of the pre-treatment plans were evaluated on daily anatomy as visible on the repeated MRIs and compared to online replanning. RESULTS: With online MRI-based replanning significant dosimetric improvements are obtained for the rectum, bladder, bowel and sigmoid without compromising the target dose. The amount of unintended violations of the dose constraints for target and surrounding organs could be reduced by 75% for 8 mm and 66% for 3 mm PTV margins. CONCLUSION: The use of online replanning based on the actual anatomy as seen on repeated MRI compared to online position correction for lymph node oligometastases SBRT gives beneficial dosimetric outcomes and reduces the amount of unplanned violations of dose constraints.

BACKGROUND: Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. MATERIAL AND METHODS: In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined by dose-maps from EBRT and IGABT. All PET/CT scans were re-evaluated and nodal maximal standard uptake value (SUVmax) was determined. Nodal failures were registered to planning scans and related to boosted nodes and treated volume. Relation between SUVmax and nodal control as well as the pattern of regional nodal failure were analyzed. RESULTS: Eighty-four patients were node positive. Nine patients had all metastatic nodes surgically removed. Seventy-five patients had 209 nodes boosted with EBRT. Median nodal boost dose was 62 Gy EQD2 (53-69 Gy EQD2). Median SUVmax was 6 (2-22). No patients had persistent nodal disease, but six patients recurred in a boosted node. SUVmax was significantly higher in nodes that recurred (p = 0.02). However, there was no correlation to nodal dose or volume. Twenty-one patients had a nodal failure including para-aortic nodal (PAN) metastases above the irradiated volume. Nine patients had a PAN-only failure. Patients receiving ≤ 4 cycles of weekly cisplatin had higher risk of nodal failure (p < 0.01). CONCLUSION: Current RT practice provides a high level of control in both boosted nodes and the elective irradiated regional target. However, a high nodal SUVmax is a negative prognostic predictor for nodal control. Attention should be raised to administration of a complete schedule of concurrent chemotherapy as well as treatment of para-aortic nodes.

Purpose For patients with cervical cancer the delivery of chemotherapy with radiotherapy improves survival compared with radiotherapy alone. However, high rates of acute hematologic toxicity occur when combining both therapies due to the damage of the red bone marrow (RBM). This study aimed to reduce the radiation damage to the RBM. A tool has been developed for semi-automatic delineation of the red bone marrow based on MR-only. This delineation can be included into the treatment planning process to reduce the volume of RBM irradiated in patients receiving pelvic radiation therapy. Methods 13 patients with cervical cancer were enrolled. All the patients underwent MR, CT and FDG-PET imaging. A tool for RBM determination from water and fat MR images was developed. Our MR-based RBM tool was optimized and validated with the FDG-PET scans of the patients. Results Our tool identified RBM regions in the pelvic area. The mean total volume of these regions was 34% of the pelvic bone marrow. The corresponding SUV values based on the FDG-PET scans were above the reported threshold of active/red bone marrow. Conclusion This study shows that delineations of the RBM for the radiotherapy with RBM sparing can be generated semi-automatically using MR scans only.