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.

First experimental demonstration of VMAT combined with MLC tracking for single and multi fraction lung SBRT on an MR-linac.

BACKGROUND AND PURPOSE: VMAT is not currently available on MR-linacs but could maximize plan conformality. To mitigate respiration without compromising delivery efficiency, MRI-guided MLC tumour tracking was recently developed for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) in combination with IMRT. Here, we provide a first experimental demonstration of VMAT + MLC tracking for several lung SBRT indications. MATERIALS AND METHODS: We created central patient and phantom VMAT plans (8×7.5 Gy, 2 arcs) and we created peripheral phantom plans (3×18 & 1×34 Gy, 4 arcs). A motion phantom mimicked subject-recorded respiratory motion (A‾=11 mm, f‾=0.33 Hz, drift‾=0.3 mm/min). This was monitored using 2D-cine MRI at 4 Hz to continuously realign the beam with the target. VMAT + MLC tracking performance was evaluated using 2D film dosimetry and a novel motion-encoded and time-resolved pseudo-3D dosimetry approach. RESULTS: We found an MLC leaf and jaw end-to-end latency of 328.05(±3.78) ms and 317.33(±4.64) ms, which was mitigated by a predictor. The VMAT plans required maximum MLC speeds of 12.1 cm/s and MLC tracking superimposed an additional 1.48 cm/s. A local 2%/1 mm gamma analysis with a static measurement as reference, revealed pass-rates of 28-46% without MLC tracking and 88-100% with MLC tracking for the 2D film analysis. Similarly, the pseudo-3D gamma passing-rates increased from 22-77% to 92-100%. The dose area histograms showed that MLC tracking increased the GTV D98% by 5-20% and the PTV D95% by 7-24%, giving similar target coverage as their respective static reference. CONCLUSION: MRI-guided VMAT + MLC tracking is technically feasible on the MR-linac and results in highly conformal dose distribution.

Delivered dose quantification in prostate radiotherapy using online 3D cine imaging and treatment log files on a combined 1.5T magnetic resonance imaging and linear accelerator system.

BACKGROUND AND PURPOSE: Monitoring the intrafraction motion and its impact on the planned dose distribution is of crucial importance in radiotherapy. In this work we quantify the delivered dose for the first prostate patients treated on a combined 1.5T Magnetic Resonance Imaging (MRI) and linear accelerator system in our clinic based on online 3D cine-MR and treatment log files. MATERIALS AND METHODS: A prostate intrafraction motion trace was obtained with a soft-tissue based rigid registration method with six degrees of freedom from 3D cine-MR dynamics with a temporal resolution of 8.5-16.9 s. For each fraction, all dynamics were also registered to the daily MR image used during the online treatment planning, enabling the mapping to this reference point. Moreover, each fraction's treatment log file was used to extract the timestamped machine parameters during delivery and assign it to the appropriate dynamic volume. These partial plans to dynamic volume combinations were calculated and summed to yield the delivered fraction dose. The planned and delivered dose distributions were compared among all patients for a total of 100 fractions. RESULTS: The clinical target volume underwent on average a decrease of 2.2% ± 2.9% in terms of D99% coverage while bladder V62Gy was increased by 1.6% ± 2.3% and rectum V62Gy decreased by 0.2% ± 2.2%. CONCLUSIONS: The first MR-linac dose reconstruction results based on prostate tracking from intrafraction 3D cine-MR and treatment log files are presented. Such a pipeline is essential for online adaptation especially as we progress to MRI-guided extremely hypofractionated treatments.

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.

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.

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.

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.

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 patient's 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.

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 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 patient's 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.