Simulated dosimetric impact of online replanning for stereotactic body radiation therapy of lymph node oligometastases on the 1.5T MR-linac.

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.

Physically constrained voxel-based penalty adaptation for ultra-fast IMRT planning.

Conventional treatment planning in intensity-modulated radiation therapy (IMRT) is a trial-and-error process that usually involves tedious tweaking of optimization parameters. Here, we present an algorithm that automates part of this process, in particular the adaptation of voxel-based penalties within normal tissue. Thereby, the proposed algorithm explicitly considers a priori known physical limitations of photon irradiation. The efficacy of the developed algorithm is assessed during treatment planning studies comprising 16 prostate and 5 head and neck cases. We study the eradication of hot spots in the normal tissue, effects on target coverage and target conformity, as well as selected dose volume points for organs at risk. The potential of the proposed method to generate class solutions for the two indications is investigated. Run-times of the algorithms are reported. Physically constrained voxel-based penalty adaptation is an adequate means to automatically detect and eradicate hot-spots during IMRT planning while maintaining target coverage and conformity. Negative effects on organs at risk are comparably small and restricted to lower doses. Using physically constrained voxel-based penalty adaptation, it was possible to improve the generation of class solutions for both indications. Considering the reported run-times of less than 20 s, physically constrained voxel-based penalty adaptation has the potential to reduce the clinical workload during planning and automated treatment plan generation in the long run, facilitating adaptive radiation treatments.

Towards mid-position based Stereotactic Body Radiation Therapy using online magnetic resonance imaging guidance for central lung tumours.

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac. Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk's margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins. Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; p < 0.042 ). Automatically derived margins agreed within one millimeter with manually derived margins. Conclusions: This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage.

Clinical application of a sub-fractionation workflow for intrafraction re-planning during prostate radiotherapy treatment on a 1.5 Tesla MR-Linac: A practical method to mitigate intrafraction motion.

BACKGROUND: Intrafraction motion during radiotherapy limits margin reduction and dose escalation. Magnetic resonance (MR)-guided linear accelerators (MR-Linac) have emphasised this issue by enabling intrafraction imaging. We present and clinically apply a new workflow to counteract systematic intrafraction motion during MR-guided stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: With the sub-fractionation workflow, the daily dose is delivered in multiple sequential parts (sub-fractions), each adapted to the latest anatomy. As each sub-fractionation treatment plan complies with the dose constraints, no online dose accumulation is required. Imaging and treatment planning are executed in parallel with dose delivery to minimise dead time, enabling an efficient workflow. The workflow was implemented on a 1.5 T MR-Linac and applied in 15 prostate cancer (PCa) patients treated with 5 × 7.25 Gy in two sub-fractions of 3.625 Gy (10 × 3.625 Gy in total). Intrafraction clinical target volume (CTV) motion was determined and compared to a workflow with single-plan delivery. Furthermore, required planning target volume (PTV) margins were determined. RESULTS: Average on-table time was 42.7 min. Except for two fractions, all fractions were delivered within 60 min. Average intrafraction 3D CTV displacement (±standard deviation) was 1.1 mm (± 0.7) with the sub-fractionation workflow, whereas this was up to 3.5 mm (± 2.4) without sub-fractionation. Calculated PTV margins required with sub-fractionation were 1.0 mm (left-right), 2.4 mm (cranial-caudal), and 2.6 mm (anterior-posterior). CONCLUSION: Feasibility of the sub-fractionation workflow was demonstrated in 15 PCa patients treated with two sub-fractions on a 1.5 T MR-Linac. The workflow allows for significant PTV margin reduction in these patients by reducing systematic intrafraction motion during SBRT.

Impact of magnetic resonance-guided versus conventional radiotherapy workflows on organ at risk doses in stereotactic body radiotherapy for lymph node oligometastases.

Background and purpose: Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery. Materials and methods: For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D0.5cc and D10cc values were evaluated, focusing on bowelbag and duodenum. Results: Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D0.5cc and D10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac. Conclusions: Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning.

Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients.

STUDY TYPE: Prognostic (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper. OBJECTIVE: To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT. PATIENTS AND METHODS: In 932 patients, who were treated with external radiotherapy (N=311) or brachytherapy (N=621) for their T1-3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. Associations between the different fat measurements and risk of having high-risk (according to Ash et al., PSA>20 or Gleason score≥8 or T3) disease was measured. RESULTS: The median age (IQR) was 67.0 years (62.0-71.0) and median BMI (IQR) was 25.8 (24.2-28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04-1.08], P<0.001) CONCLUSION: Patients with a higher PFD had more often aggressive prostate cancer.

Influence of eye movement on lens dose and optic nerve target coverage during craniospinal irradiation.

PURPOSE: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. METHODS: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. RESULTS: Mean eye structures' shift from neutral position was greatest in caudal gaze; -5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98OON) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range -8.1 to 10.0 Gy], and mean D98OON decreased up to 3.3 Gy [total ΔD98OON range -13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98OON significantly changed in 1 of 10 volunteers. CONCLUSION: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose.

Prone vs. supine accelerated partial breast irradiation on an MR-Linac: A planning study.

BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort. MATERIALS AND METHODS: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor <3 cm underwent 1.5 T MRI in prone and supine position. The tumor or tumor bed was delineated as GTV and a 2 cm CTV-margin and 0.5 cm PTV-margin were added. 1.5 T MR-Linac treatment plans (5 × 5.2 Gy) with 11 beams were created for both positions in each patient. We evaluated the number of plans that achieved the planning constraints and performed a dosimetric comparison between prone and supine position using the Wilcoxon signed-rank test (p-value <0.01 for significance). Patient experience during scanning was evaluated with a questionnaire. RESULTS: All 40 plans met the target coverage and OAR constraints, regardless of position. Heart Dmean was not significantly different (1.07 vs. 0.79 Gy, p-value: 0.027). V5Gy to the ipsilateral lung (4.4% vs. 9.8% median, p-value 0.009) and estimated delivery time (362 vs. 392 s, p-value: 0.003) were significantly lower for prone position. PTV coverage and dose to other OAR were comparable between positions. The majority of patients (13/20) preferred supine position. CONCLUSION: APBI on the MR-Linac is dosimetrically feasible in prone and supine position. Mean heart dose was similar in both positions. Ipsilateral lung V5Gy was lower in prone position.

Dosimetric feasibility of hypofractionation for SBRT treatment of lymph node oligometastases on the 1.5T MR-linac.

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/ß = 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.

Comparison of Library of Plans with two daily adaptive strategies for whole bladder radiotherapy.

BACKGROUND AND PURPOSE: Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments. METHODS AND MATERIALS: Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images. RESULTS: MRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0-23%) compared to 0% (0-20%) and 0% (0-10%), respectively. CONCLUSIONS: Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.

Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness.

OBJECTIVE: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC. PATIENTS AND METHODS: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: <25, 25-75 and >75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined. RESULTS: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease. CONCLUSIONS: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.

Clinical implementation of MRI-based organs-at-risk auto-segmentation with convolutional networks for prostate radiotherapy.

BACKGROUND: Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT). PURPOSE: In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI. MATERIALS AND METHODS: We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD95), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD95 and mean distances were calculated against the clinically used delineations. RESULTS: DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved. CONCLUSION: High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study.

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.

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.

Evaluation of plan adaptation strategies for stereotactic radiotherapy of lymph node oligometastases using online magnetic resonance image guidance.

BACKGROUND AND PURPOSE: Recent studies have shown that the use of magnetic resonance (MR) guided online plan adaptation yields beneficial dosimetric values and reduces unplanned violations of the dose constraints for stereotactic body radiation therapy (SBRT) of lymph node oligometastases. The purpose of this R-IDEAL stage 0 study was to determine the optimal plan adaptation approach for MR-guided SBRT treatment of lymph node oligometastases. MATERIALS AND METHODS: Using pre-treatment computed tomography (CT) and repeated MR data from five patients with in total 17 pathological lymph nodes, six different methods of plan adaptation were performed on the daily MRI and contours. To determine the optimal plan adaptation approach for treatment of lymph node oligometastases, the adapted plans were evaluated using clinical dose criteria and the time required for performing the plan adaptation. RESULTS: The average time needed for the different plan adaptation methods ranged between 11 and 119 s. More advanced adaptation methods resulted in more plans that met the clinical dose criteria [range, 0-16 out of 17 plans]. The results show a large difference between target coverage achieved by the different plan adaptation methods. CONCLUSION: Results suggested that multiple plan adaptation methods, based on plan adaptation on the daily anatomy, were feasible for MR-guided SBRT treatment of lymph node oligometastases. The most advanced method, in which a full online replanning was performed by segment shape and weight optimization after fluence optimization, yielded the most favourable dosimetric values and could be performed within a time-frame acceptable (<5 min) for MR-guided treatment.

Individual lymph nodes: "See it and Zap it".

BACKGROUND AND PURPOSE: With magnetic resonance imaging (MRI)-guided radiotherapy systems such as the 1.5T MR-linac the daily anatomy can be visualized before, during and after radiation delivery. With these treatment systems, seeing metastatic nodes with MRI and zapping them with stereotactic body radiotherapy (SBRT) comes into reach. The purpose of this study is to investigate different online treatment planning strategies and to determine the planning target volume (PTV) margin needed for adequate target coverage when treating lymph node oligometastases with SBRT on the 1.5T MR-linac. MATERIALS AND METHODS: Ten patients were treated for single pelvic or para-aortic lymph node metastases on the 1.5T MR-linac with a prescribed dose of 5x7Gy with a 3 mm isotropic GTV- PTV margin. Based on the daily MRI and actual contours, a completely new treatment plan was generated for each session (adapt to shape, ATS). These were compared with plans optimized on pre-treatment CT contours after correcting for the online target position (adapt to position, ATP). At the end of each treatment session, a post-radiation delivery MRI was acquired on which the GTV was delineated to evaluate the GTV coverage and PTV margins. RESULTS: The median PTV V35Gy was 99.9% [90.7-100%] for the clinically delivered ATS plans compared to 93.6% [76.3-99.7%] when using ATP. The median GTV V35Gy during radiotherapy delivery was 100% [98-100%] on the online planning and post-delivery MRIs for ATS and 100% [93.9-100%] for ATP, respectively. The applied 3 mm isotropic PTV margin is considered adequate. CONCLUSION: For pelvic and para-aortic metastatic lymph nodes, online MRI-guided adaptive treatment planning results in adequate PTV and GTV coverage when taking the actual patient anatomy into account (ATS). Generally, GTV coverage remained adequate throughout the treatment session for both adaptive planning strategies. "Seeing and zapping" metastatic lymph nodes comes within reach for MRI-guided SBRT.

Feasibility of stereotactic radiotherapy using a 1.5 T MR-linac: Multi-fraction treatment of pelvic lymph node oligometastases.

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.

Adaptive radiotherapy: The Elekta Unity MR-linac concept.

BACKGROUND AND PURPOSE: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods. MATERIALS AND METHODS: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured. RESULTS: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases. CONCLUSION: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Evaluation of Online Plan Adaptation Strategies for the 1.5T MR-linac Based on "First-In-Man" Treatments.

The superior soft tissue contrast provided by magnetic resonance (MR) images on the 1.5T MR-linac allows for the incorporation of patient anatomy information. In this retrospective case study, we present the simulated dosimetric effects and timings of full online replanning as compared to the five plan adaptation methods currently available on the 1.5T MR-linac treatment system. For this case, it is possible to create treatment plans with all six methods within a time slot suitable for an online treatment procedure. However, large dosimetric differences between the plan adaptation methods and full online replanning are present with regards to target coverage and dose to organs at risk (OARs).

Fast online replanning for interfraction rotation correction in prostate radiotherapy.

PURPOSE: To enable fast online replanning for prostate radiotherapy with the inclusion of interfraction rotations and translations and investigate the possibility for margin reduction via this regime. METHODS: Online daily replanning for a 35-fraction treatment for five prostate cases is simulated while accounting for anatomical transformations derived from fiducial marker data available in our clinic. Two online replanning strategies were simulated, compensating for: (a) rotation-only in combination with a couch shift and (b) both translation and rotation without a couch shift. They were compared against our current clinical protocol consisting of a single offline plan used over all fractions with daily couch repositioning (translations only). For every patient, the above methods were generated for several planning margins (0-8 mm with 2 mm increments) in order to assess the performance of online replanning in terms of target coverage and investigate the possible dosimetric benefit for the organs at risk. The daily DVHs for each treatment strategy were used for evaluation and the non tumor integral dose (NTID) for the different margins was calculated in order to quantify the overall reduction of the delivered energy to the patient. RESULTS: Our system is able to generate a daily automated prostate plan in less than 2 min. For every patient, the daily treatment plans produce similar dose distributions to the original approved plan (average CTV D99 relative difference: 0.2%). The inclusion of both shifts and rotations can be effectively compensated via replanning among all planning margins (average CTV D99 difference: 0.01 Gy between the two replanning regimes). Online replanning is able to maintain target coverage among all margins, while - as expected - the conventional treatment plan is increasingly affected by the interfraction rotations as the margins shrink (average CTV D99 decrease: 0.2 Gy at 8 mm to 2.9 Gy at 0 mm margin). The possible gain in total delivered energy to the patient was quantified by the decreased NTID ranging from 12.6% at 6 mm to 32.9% at 0 mm. CONCLUSIONS: We demonstrate that fast daily replanning can be utilized to account for daily rotations and translations based on the daily positioning protocol. A daily plan can be generated from scratch in less than 2 min making it suitable for online application. Given the large magnitude of prostate rotation around the LR axis, online correction for daily rotations can be beneficial even for the clinical 8 mm margin and could be utilized for treatments with small margin reduction mainly limited then by anatomical deformations and intrafraction motion. Our online replanning pipeline can be used in future treatments with online MR guidance that can lead to further safe reduction of the planning margins.

Interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation.

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.