C Kontaxis

Towards adaptive IMRT sequencing for the MR-linac

The MRI linear accelerator (MR-linac) that is currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to track the patients target(s) and Organ(s) At Risk during radiation delivery. In this paper, we present a treatment planning system for intensity-modulated radiotherapy (IMRT). It is capable of Adaptive Radiotherapy and consists of a GPU Monte Carlo dose engine, an inverse dose optimization algorithm and a novel adaptive sequencing algorithm. The system is able to compensate for patient anatomy changes and enables radiation delivery immediately from the first calculated segment. IMRT plans meeting all clinical constraints were generated for two breast cases, one spinal bone metastasis case, two prostate cases with integrated boost regions and one head and neck case. These plans were generated by the segment weighted version of our algorithm, in a 0 T environment in order to test the feasibility of the new sequencing strategy in current clinical conditions, yielding very small differences between the fluence and sequenced distributions. All plans went through stringent experimental quality assurance on Delta4 and passed all clinical tests currently performed in our institute. A new inter-fraction adaptation scheme built on top of this algorithm is also proposed that enables convergence to the ideal dose distribution without the need of a final segment weight optimization. The first results of this method confirm that convergence is achieved within the first fractions of the treatment. These features combined will lead to a fully adaptive intra-fraction planning system able to take into account patient anatomy updates during treatment.

A new methodology for inter- and intrafraction plan adaptation for the MR-linac

The new era of hybrid MRI and linear accelerator machines, including the MR-linac currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to provide the actual anatomy and real-time anatomy changes of the patients target(s) and organ(s) at risk (OARs) during radiation delivery. In order to be able to take advantage of this input, a new generation of treatment planning systems is needed, that will allow plan adaptation to the latest anatomy state in an online regime. In this paper, we present a treatment planning algorithm for intensity-modulated radiotherapy (IMRT), which is able to compensate for patient anatomy changes. The system consists of an iterative sequencing loop open to anatomy updates and an inter- and intrafraction adaptation scheme that enables convergence to the ideal dose distribution without the need of a final segment weight optimization (SWO). The ability of the system to take into account organ motion and adapt the plan to the latest anatomy state is illustrated using artificial baseline shifts created for three different kidney cases. Firstly, for two kidney cases of different target volumes, we show that the system can account for intrafraction motion, delivering the intended dose to the target with minimal dose deposition to the surroundings compared to conventional plans. Secondly, for a third kidney case we show that our algorithm combined with the interfraction scheme can be used to deliver the prescribed dose while adapting to the changing anatomy during multi-fraction treatments without performing a final SWO.

On-line MR imaging for dose validation of abdominal radiotherapy

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial.Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant.In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur.The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions.In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose.Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  -2.3-1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  -2.5 to 1.9 Gy could be traced back.

Dosimetric feasibility of intensity modulated proton therapy in a transverse magnetic field of 1.5 T

Proton therapy promises higher dose conformality in comparison with regular radiotherapy techniques. Also, image guidance has an increasing role in radiotherapy and MRI is a prime candidate for this imaging. Therefore, in this paper the dosimetric feasibility of Intensity Modulated Proton Therapy (IMPT) in a magnetic field of 1.5 T and the effect on the generated dose distributions compared to those at 0 T is evaluated, using the Monte Carlo software TOol for PArticle Simulation (TOPAS). For three different anatomic sites IMPT plans are generated. It is shown that the generation of an IMPT plan in a magnetic field is feasible, the impact of the magnetic field is small, and the resulting dose distributions are equivalent for 0 T and 1.5 T. Also, the framework of Monte Carlo simulation combined with an inverse optimization method can be used to generate IMPT plans. These plans can be used in future dosimetric comparisons with e.g. IMRT and conventional IMPT. Finally, this study shows that IMPT in a 1.5 T magnetic field is dosimetrically feasible.

Towards fast online intrafraction replanning for free-breathing stereotactic body radiation therapy with the MR-linac

The hybrid MRI-radiotherapy machines, like the MR-linac (Elekta AB, Stockholm, Sweden) installed at the UMC Utrecht (Utrecht, The Netherlands), will be able to provide real-time patient imaging during treatment. In order to take advantage of the systems capabilities and enable online adaptive treatments, a new generation of software should be developed, ranging from motion estimation to treatment plan adaptation. In this work we present a proof of principle adaptive pipeline designed for high precision stereotactic body radiation therapy (SBRT) suitable for sites affected by respiratory motion, like renal cell carcinoma (RCC). We utilized our research MRL treatment planning system (MRLTP) to simulate a single fraction 25 Gy free-breathing SBRT treatment for RCC by performing inter-beam replanning for two patients and one volunteer. The simulated pipeline included a combination of (pre-beam) 4D-MRI and (online) 2D cine-MR acquisitions. The 4DMRI was used to generate the mid-position reference volume, while the cine-MRI, via an in-house motion model, provided three-dimensional (3D) deformable vector fields (DVFs) describing the anatomical changes during treatment. During the treatment fraction, at an inter-beam interval, the mid-position volume of the patient was updated and the delivered dose was accurately reconstructed on the underlying motion calculated by the model. Fast online replanning, targeting the latest anatomy and incorporating the previously delivered dose was then simulated with MRLTP. The adaptive treatment was compared to a conventional mid-position SBRT plan with a 3 mm planning target volume margin reconstructed on the same motion trace. We demonstrate that our system produced tighter dose distributions and thus spared the healthy tissue, while delivering more dose to the target. The pipeline was able to account for baseline variations/drifts that occurred during treatment ensuring target coverage at the end of the treatment fraction.

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.

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to [Formula: see text] of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

SU‐C‐17A‐07: The Development of An MR Accelerator‐Enabled Planning‐To‐Delivery Technique for Stereotactic Palliative Radiotherapy Treatment of Spinal Metastases

PURPOSE To develop an MR accelerator-enabled online planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases. The technical challenges include; automated stereotactic treatment planning, online MR-based dose calculation and MR guidance during treatment. METHODS Using the CT data of 20 patients previously treated at our institution, a class solution for automated treatment planning for spinal bone metastases was created. For accurate dose simulation right before treatment, we fused geometrically correct online MR data with pretreatment CT data of the target volume (TV). For target tracking during treatment, a dynamic T2-weighted TSE MR sequence was developed. An in house developed GPU based IMRT optimization and dose calculation algorithm was used for fast treatment planning and simulation. An automatically generated treatment plan developed with this treatment planning system was irradiated on a clinical 6 MV linear accelerator and evaluated using a Delta4 dosimeter. RESULTS The automated treatment planning method yielded clinically viable plans for all patients. The MR-CT fusion based dose calculation accuracy was within 2% as compared to calculations performed with original CT data. The dynamic T2-weighted TSE MR Sequence was able to provide an update of the anatomical location of the TV every 10 seconds. Dose calculation and optimization of the automatically generated treatment plans using only one GPU took on average 8 minutes. The Delta4 measurement of the irradiated plan agreed with the dose calculation with a 3%/3mm gamma pass rate of 86.4%. CONCLUSIONS The development of an MR accelerator-enabled planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases was presented. Future work will involve developing an intrafraction motion adaptation strategy, MR-only dose calculation, radiotherapy quality-assurance in a magnetic field, and streamlining the entire treatment process on an MR accelerator.

SU-F-J-105: Towards a Novel Treatment Planning Pipeline Delivering Pareto- Optimal Plans While Enabling Inter- and Intrafraction Plan Adaptation

PURPOSE To develop a new IMRT treatment planning methodology suitable for the new generation of MR-linear accelerator machines. The pipeline is able to deliver Pareto-optimal plans and can be utilized for conventional treatments as well as for inter- and intrafraction plan adaptation based on real-time MR-data. METHODS A Pareto-optimal plan is generated using the automated multicriterial optimization approach Erasmus-iCycle. The resulting dose distribution is used as input to the second part of the pipeline, an iterative process which generates deliverable segments that target the latest anatomical state and gradually converges to the prescribed dose. This process continues until a certain percentage of the dose has been delivered. Under a conventional treatment, a Segment Weight Optimization (SWO) is then performed to ensure convergence to the prescribed dose. In the case of inter- and intrafraction adaptation, post-processing steps like SWO cannot be employed due to the changing anatomy. This is instead addressed by transferring the missing/excess dose to the input of the subsequent fraction. In this work, the resulting plans were delivered on a Delta4 phantom as a final Quality Assurance test. RESULTS A conventional static SWO IMRT plan was generated for two prostate cases. The sequencer faithfully reproduced the input dose for all volumes of interest. For the two cases the mean relative dose difference of the PTV between the ideal input and sequenced dose was 0.1% and -0.02% respectively. Both plans were delivered on a Delta4 phantom and passed the clinical Quality Assurance procedures by achieving 100% pass rate at a 3%/3mm gamma analysis. CONCLUSION We have developed a new sequencing methodology capable of online plan adaptation. In this work, we extended the pipeline to support Pareto-optimal input and clinically validated that it can accurately achieve these ideal distributions, while its flexible design enables inter- and intrafraction plan adaptation. This research is financially supported by Elekta AB, Stockholm, Sweden.

SU-D-207A-07: The Effects of Inter-Cycle Respiratory Motion Variation On Dose Accumulation in Single Fraction MR-Guided SBRT Treatment of Renal Cell Carcinoma.

PURPOSE To assess the dose deposition in simulated single-fraction MR-Linac treatments of renal cell carcinoma, when inter-cycle respiratory motion variation is taken into account using online MRI. METHODS Three motion characterization methods, with increasing complexity, were compared to evaluate the effect of inter-cycle motion variation and drifts on the accumulated dose for an SBRT kidney MR-Linac treatment: 1) STATIC, in which static anatomy was assumed, 2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, based on the respiratory phase and 3) PCA, in which 3D volumes were generated using a PCA-model, enabling the detection of inter-cycle variations and drifts. An experimental ITV-based kidney treatment was simulated in a 1.5T magnetic field on three volunteer datasets. For each volunteer a retrospectively sorted 4D-MRI (ten respiratory phases) and fast 2D cine-MR images (temporal resolution = 476ms) were acquired to simulate MR-imaging during radiation. For each method, the high spatio-temporal resolution 3D volumes were non-rigidly registered to obtain deformation vector fields (DVFs). Using the DVFs, pseudo-CTs (generated from the 4D-MRI) were deformed and the dose was accumulated for the entire treatment. The accuracies of all methods were independently determined using an additional, orthogonal 2D-MRI slice. RESULTS Motion was most accurately estimated using the PCA method, which correctly estimated drifts and inter-cycle variations (RMSE=3.2, 2.2, 1.1mm on average for STATIC, AVG-RESP and PCA, compared to the 2DMRI slice). Dose-volume parameters on the ITV showed moderate changes (D99=35.2, 32.5, 33.8Gy for STATIC, AVG-RESP and PCA). AVG-RESP showed distinct hot/cold spots outside the ITV margin, which were more distributed for the PCA scenario, since inter-cycle variations were not modeled by the AVG-RESP method. CONCLUSION Dose differences were observed when inter-cycle variations were taken into account. The increased inter-cycle randomness in motion as captured by the PCA model mitigates the local (erroneous) hotspots estimated by the AVG-RESP method.