Comparison of pancreatic respiratory motion management with three abdominal corsets for particle radiation therapy: Case study.

BACKGROUND AND PURPOSE: Abdominal organ motion seriously compromises the targeting accuracy for particle therapy in patients with pancreatic adenocarcinoma. This study compares three different abdominal corsets regarding their ability to reduce pancreatic motion and their potential usability in particle therapy. MATERIALS AND METHODS: A patient-individualized polyurethane (PU), a semi-individualized polyethylene (PE), and a patient-individualized three-dimensional-scan based polyethylene (3D-PE) corset were manufactured for one healthy volunteer. Time-resolved volumetric four-dimensional-magnetic resonance imaging (4D-MRI) and single-slice two-dimensional (2D) cine-MRI scans were acquired on two consecutive days to compare free-breathing motion patterns with and without corsets. The corset material properties, such as thickness variance, material homogeneity in Hounsfield units (HU) on computed tomography (CT) scans, and manufacturing features were compared. The water equivalent ratio (WER) of corset material samples was measured using a multi-layer ionization chamber for proton energies of 150 and 200 MeV. RESULTS: All corsets reduced the pancreatic motion on average by 9.6 mm in inferior-superior and by 3.2 mm in anterior-posterior direction. With corset, the breathing frequency was approximately doubled and the day-to-day motion variations were reduced. The WER measurements showed an average value of 0.993 and 0.956 for the PE and 3DPE corset, respectively, and of 0.298 for the PU corset. The PE and 3DPE corsets showed a constant thickness of 2.8 ± 0.2 and 3.8 ± 0.2 mm, respectively and a homogeneous material composition with a standard deviation (SD) of 31 and 32 HU, respectively. The PU corset showed a variable thickness of 4.2 - 25.6 mm and a heterogeneous structure with air inclusions with an SD of 113 HU. CONCLUSION: Abdominal corsets may be effective devices to reduce pancreatic motion. For particle therapy, PE-based corsets are preferred over PU-based corset due to their material homogeneity and constant thickness.

Comparing the effectiveness and efficiency of various gating approaches for PBS proton therapy of pancreatic cancer using 4D-MRI datasets.

Abdominal organ motion may lead to considerable uncertainties in pencil-beam scanning (PBS) proton therapy of pancreatic cancer. Beam gating, where irradiation only occurs in certain breathing phases in which the gating conditions are fulfilled, may be an option to reduce the interplay effect between tumor motion and the scanning beam. This study aims to, first, determine suitable gating windows with respect to effectiveness (low interplay effect) and efficiency (high duty cycles). Second, it investigates whether beam gating allows for a better mitigation of the interplay effect along the treatment course than free-breathing irradiations. Based on synthetic 4D-CTs, generated by warping 3D-CTs with vector fields extracted from time-resolved magnetic resonance imaging (4D-MRI) for 8 pancreatic cancer patients, 4D dose calculations (4DDC) were performed to analyze the duty cycle and homogeneity index HI = d5/d95 for four different gating scenarios. These were based on either fixed threshold values of CTV (clinical target volume) mean or maximum motion amplitudes (5 mm), relative CTV motion amplitudes (30%) or CTV overlap criteria (95%), respectively. 4DDC for 28-fractions treatment courses were performed with fixed and variable initial breathing phases to investigate the fractionation-induced mitigation of the interplay effect. Gating criteria, based on patient-specific relative 30% CTV motion amplitudes, showed the significantly best HI values with sufficient duty cycles, in contrast to inferior results by either fixed gating thresholds or overlap criteria. For gated treatments with 28 fractions, less fractionation-induced mitigation of the interplay effect was observed for gating criteria with gating windows ⩾30%, compared to free-breathing treatments. The gating effectiveness for multiple fractions was improved by allowing a variable initial breathing phase. Gating with relative amplitude thresholds are effective for proton therapy of pancreatic cancer. By combining beam gating with variable initial breathing phases, a pronounced mitigation of the interplay effect by fractionation can be achieved.

4DMRI-based investigation on the interplay effect for pencil beam scanning proton therapy of pancreatic cancer patients.

BACKGROUND: Time-resolved volumetric magnetic resonance imaging (4DMRI) offers the potential to analyze 3D motion with high soft-tissue contrast without additional imaging dose. We use 4DMRI to investigate the interplay effect for pencil beam scanning (PBS) proton therapy of pancreatic cancer and to quantify the dependency of residual interplay effects on the number of treatment fractions. METHODS: Based on repeated 4DMRI datasets for nine pancreatic cancer patients, synthetic 4DCTs were generated by warping static 3DCTs with 4DMRI deformation vector fields. 4D dose calculations for scanned proton therapy were performed to quantify the interplay effect by CTV coverage (v95) and dose homogeneity (d5/d95) for incrementally up to 28 fractions. The interplay effect was further correlated to CTV motion characteristics. For quality assurance, volume and mass conservation were evaluated by Jacobian determinants and volume-density comparisons. RESULTS: For the underlying patient cohort with CTV motion amplitudes < 15 mm, we observed significant correlations between CTV motion amplitudes and both the length of breathing cycles and the interplay effect. For individual fractions, tumor underdosage down to v95 = 70% was observed with pronounced dose heterogeneity (d5/d95 = 1.3). For full × 28 fractionated treatments, we observed a mitigation of the interplay effect with increasing fraction numbers. On average, after seven fractions, a CTV coverage with 95-107% of the prescribed dose was reached with sufficient dose homogeneity. For organs at risk, no significant differences were found between the static and accumulated dose plans for 28 fractions. CONCLUSION: Intrafractional organ motion exhibits a large interplay effect for PBS proton therapy of pancreatic cancer. The interplay effect correlates with CTV motion, but can be mitigated efficiently by fractionation, mainly due to different breathing starting phases in fractionated treatments. For hypofractionated treatments, a further restriction of motion may be required. Repeated 4DMRI measurements are a viable tool for pre- and post-treatment evaluations of the interplay effect.

4D dose calculation for pencil beam scanning proton therapy of pancreatic cancer using repeated 4DMRI datasets.

4D magnetic resonance imaging (4DMRI) has a high potential for pancreatic cancer treatments using proton therapy, by providing time-resolved volumetric images with a high soft-tissue contrast without exposing the patient to any additional imaging dose. In this study, we aim to show the feasibility of 4D treatment planning for pencil beam scanning (PBS) proton therapy of pancreatic cancer, based on five repeated 4DMRI datasets and 4D dose calculations (4DDC) for one pancreatic cancer patient. To investigate the dosimetric impacts of organ motion, deformation vector fields were extracted from 4DMRI, which were then used to warp a static CT of the patient, so as to generate synthetic 4DCT (4DCT-MRI). CTV motion amplitudes <15 mm were observed for this patient. The results from 4DDC show pronounced interplay effects in the CTV with dose homogeneity d5/d95 and dose coverage v95 being 1.14 and 91%, respectively, after a single fraction of the treatment. An averaging effect was further observed when increasing the number of fractions. Motion effects can become less dominant and dose homogeneity d5/d95 = 1.03 and dose coverage v95 = [Formula: see text] within the CTV can be achieved after 28 fractions. The observed inter-fractional organ and tumor motion variations underline the importance of 4D imaging before and during PBS proton therapy.

Correlation between intrafractional motion and dosimetric changes for prostate IMRT: Comparison of different adaptive strategies.

PURPOSE: To retrospectively analyze and estimate the dosimetric benefit of online and offline motion mitigation strategies for prostate IMRT. METHODS: Intrafractional motion data of 21 prostate patients receiving intensity-modulated radiotherapy was acquired with an electromagnetic tracking system. Target trajectories of 734 fractions were analyzed per delivered multileaf-collimator segment in five motion metrics: three-dimensional displacement, distance from beam axis (DistToBeam), and three orthogonal components. Time-resolved dose calculations have been performed by shifting the target according to the sampled motion for the following scenarios: without adaptation, online-repositioning with a minimum threshold of 3 mm, and an offline approach using a modified field order applying horizontal before vertical beams. Change of D95 (targets) or V65 (organs at risk) relative to the static case, that is, ΔD95 or ΔV65, was extracted per fraction in percent. Correlation coefficients (CC) between the motion metrics and the dose metrics were extracted. Mean of patient-wise CC was used to evaluate the correlation of motion metric and dosimetric changes. Mean and standard deviation of the patient-wise correlation slopes (in %/mm) were extracted. RESULTS: For ΔD95 of the prostate, mean DistToBeam per fraction showed the highest correlation for all scenarios with a relative change of -0.6 ± 0.7%/mm without adaptation and -0.4 ± 0.5%/mm for the repositioning and field order strategies. For ΔV65 of the bladder and the rectum, superior-inferior and posterior-anterior motion components per fraction showed the highest correlation, respectively. The slope of bladder (rectum) was 14.6 ± 5.8 (15.1 ± 6.9) %/mm without adaptation, 14.0 ± 4.9 (14.5 ± 7.4) %/mm for repositioning with 3 mm, and 10.6 ± 2.5 (8.1 ± 4.6) %/mm for the field order approach. CONCLUSIONS: The correlation slope is a valuable concept to estimate dosimetric deviations from static plan quality directly based on the observed motion. For the prostate, both mitigation strategies showed comparable benefit. For organs at risk, the field order approach showed less sensitive response regarding motion and reduced interpatient variation.

Robustness of target dose coverage to motion uncertainties for scanned carbon ion beam tracking therapy of moving tumors.

Beam tracking with scanned carbon ion radiotherapy achieves highly conformal target dose by steering carbon pencil beams to follow moving tumors using real-time magnetic deflection and range modulation. The purpose of this study was to evaluate the robustness of target dose coverage from beam tracking in light of positional uncertainties of moving targets and beams. To accomplish this, we simulated beam tracking for moving targets in both water phantoms and a sample of lung cancer patients using a research treatment planning system. We modeled various deviations from perfect tracking that could arise due to uncertainty in organ motion and limited precision of a scanned ion beam tracking system. We also investigated the effects of interfractional changes in organ motion on target dose coverage by simulating a complete course of treatment using serial (weekly) 4DCTs from six lung cancer patients. For perfect tracking of moving targets, we found that target dose coverage was high ([Formula: see text] was 94.8% for phantoms and 94.3% for lung cancer patients, respectively) but sensitive to changes in the phase of respiration at the start of treatment and to the respiratory period. Phase delays in tracking the moving targets led to large degradation of target dose coverage (up to 22% drop for a 15° delay). Sensitivity to technical uncertainties in beam tracking delivery was minimal for a lung cancer case. However, interfractional changes in anatomy and organ motion led to large decreases in target dose coverage (target coverage dropped approximately 8% due to anatomy and motion changes after 1 week). Our findings provide a better understand of the importance of each of these uncertainties for beam tracking with scanned carbon ion therapy and can be used to inform the design of future scanned ion beam tracking systems.

Four-dimensional patient dose reconstruction for scanned ion beam therapy of moving liver tumors.

PURPOSE: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. METHODS AND MATERIALS: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)-weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V95) and 107% (V107) of the planned doses. RESULTS: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V95 and V107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V95 > 87%, SD < 3%) and overdose (mean V107 < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. CONCLUSIONS: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.

Experimental verification of a real-time compensation functionality for dose changes due to target motion in scanned particle therapy.

PURPOSE: Implementation and experimental assessment of a real-time dose compensation system for beam tracking in scanned carbon beam therapy of intrafractionally moving targets. METHODS: A real-time dose compensation functionality has been developed and implemented at the experimental branch of the beam tracking system at GSI Helmholtzzentrum für Schwerionenforschung (GSI). Treatment plans for different target geometries have been optimized. They have been delivered using scanned carbon ions with beam tracking (BT) and real-time dose compensation combined with beam tracking (RDBT), respectively. Target motion was introduced by a rotating table. Dose distributions were assessed by ionization chamber measurements and dose reconstructions. These distributions have been compared to stationary delivery for BT as well as RDBT. Additionally simulations have been performed to investigate the dependence of delivered dose distributions on varying motion starting phases for BT and RDBT, respectively. RESULTS: Average measured dose differences between static delivery and motion influenced delivery could be reduced from 27-68 mGy when BT was used to 12-37 mGy when RDBT was used. Nominal dose was 1000 mGy. Simulated dose deliveries showed improvements in dose delivery and robustness against varying starting motion phases when RDBT was used. CONCLUSIONS: A real-time dose compensation functionality extending the existing beam tracking functionality has been implemented and verified by measurements. Measurements and simulated dose deliveries show that real-time dose compensation can substantially improve delivered dose distributions for large rotational target motion compared to beam tracking alone.

Dosimetric precision of an ion beam tracking system.

BACKGROUND: Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams. METHODS: A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion. Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system. RESULTS: All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements. CONCLUSIONS: The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems.

Ion-optical studies for a range adaptation method in ion beam therapy using a static wedge degrader combined with magnetic beam deflection.

Fast radiological range adaptation of the ion beam is essential when target motion is mitigated by beam tracking using scanned ion beams for dose delivery. Electromagnetically controlled deflection of a well-focused ion beam on a small static wedge degrader positioned between two dipole magnets, inside the beam delivery system, has been considered as a fast range adaptation method. The principle of the range adaptation method was tested in experiments and Monte Carlo simulations for the therapy beam line at the GSI Helmholtz Centre for Heavy Ions Research. Based on the simulations, ion optical settings of beam deflection and realignment of the adapted beam were experimentally applied to the beam line, and additional tuning was manually performed. Different degrader shapes were employed for the energy adaptation. Measured and simulated beam profiles, i.e. lateral distribution and range in water at isocentre, were analysed and compared with the therapy beam values for beam scanning. Deflected beam positions of up to +/-28 mm on degrader were performed which resulted in a range adaptation of up to +/-15 mm water equivalence (WE). The maximum deviation between the measured adapted range from the nominal range adaptation was below 0.4 mm WE. In experiments, the width of the adapted beam at the isocentre was adjustable between 5 and 11 mm full width at half maximum. The results demonstrate the feasibility/proof of the proposed range adaptation method for beam tracking from the beam quality point of view.

4D in-beam positron emission tomography for verification of motion-compensated ion beam therapy.

PURPOSE: Clinically safe and effective treatment of intrafractionally moving targets with scanned ion beams requires dedicated delivery techniques such as beam tracking. Apart from treatment delivery, also appropriate methods for validation of the actual tumor irradiation are highly desirable, In this contribution the feasibility of four-dimensionally (space and time) resolved, motion-compensated in-beam positron emission tomography (4DibPET) was addressed in experimental studies with scanned carbon ion beams. METHODS: A polymethyl methracrylate block sinusoidally moving left-right in beam's eye view was used as target. Radiological depth changes were introduced by placing a stationary ramp-shaped absorber proximal of the moving target. Treatment delivery was compensated for motion by beam tracking. Time-resolved, motion-correlated in-beam PET data acquisition was performed during beam delivery with tracking the moving target and prolonged after beam delivery first with the activated target still in motion and, finally, with the target at rest. Motion-compensated 4DibPET imaging was implemented and the results were compared to a stationary reference irradiation of the same treatment field. Data were used to determine feasibility of 4DibPET but also to evaluate offline in comparison to in-beam PET acquisition. RESULTS: 4D in-beam as well as offline PET imaging was found to be feasible and offers the possibility to verify the correct functioning of beam tracking. Motion compensation of the imaged beta(+)-activity distribution allows recovery of the volumetric extension of the delivered field for direct comparison with the reference stationary condition. Observed differences in terms of lateral field extension and penumbra in the direction of motion were typically less than 1 mm for both imaging strategies in comparison to the corresponding reference distributions. However, in-beam imaging retained a better spatial correlation of the measured activity with the delivered dose. CONCLUSIONS: 4DibPET is a feasible and promising method to validate treatment delivery of scanned ion beams to moving targets. Further investigations will focus on more complex geometries and treatment planning studies with clinical data.

Speed and accuracy of a beam tracking system for treatment of moving targets with scanned ion beams.

The technical performance of an integrated three-dimensional carbon ion pencil beam tracking system that was developed at GSI was investigated in phantom studies. Aim of the beam tracking system is to accurately treat tumours that are subject to respiratory motion with scanned ion beams. The current system provides real-time control of ion pencil beams to track a moving target laterally using the scanning magnets and longitudinally with a dedicated range shifter. The system response time was deduced to be approximately 1 ms for lateral beam tracking. The range shifter response time has been measured for various range shift amounts. A value of 16 +/- 2 ms was achieved for a water equivalent shift of 5 mm. An additional communication delay of 11 +/- 2 ms was taken into account in the beam tracking process via motion prediction. Accuracy of the lateral beam tracking was measured with a multi-wire position detector to < or =0.16 mm standard deviation. Longitudinal beam tracking accuracy was parameterized based on measured responses of the range shifter and required time durations to maintain a specific particle range. For example, 5 mm water equivalence (WE) longitudinal beam tracking results in accuracy of 1.08 and 0.48 mm WE in root mean square for time windows of 10 and 50 ms, respectively.

Gated irradiation with scanned particle beams.

PURPOSE: To demonstrate mitigation of the interplay effects of scanned particle beams and residual target motion within a gating window by increased overlap of pencil beams. METHODS AND MATERIALS: Lateral overlap was increased by increasing the pencil beam widths or by decreasing the distance between the pencil beams (scan grid). Longitudinal overlap was increased by reducing the distance between iso-range slices. For scanned carbon ion beams, simulation studies were performed and validated experimentally to determine the required parameters for different residual motion characteristics. The dose distributions were characterized by the maximal local deviations representing local over- and underdosage. RESULTS: For residual lateral motion, the local deviations were <5% for 2, 4, and 7 mm residual motion within the gating window for a 2-mm scan grid and pencil beams of 10, 14, and 18 mm full width at half maximum, respectively. Decreasing the iso-range slice distance from 3 mm to 1 mm effectively mitigated

Target motion tracking with a scanned particle beam.

Treatment of moving targets with scanned particle beams results in local over- and under-dosage due to interplay of beam and target motion. To mitigate the impact of respiratory motion, a motion tracking system has been developed and integrated in the therapy control system at Gesellschaft für Schwerionenforschung. The system adapts pencil beam positions as well as the beam energy according to target motion to irradiate the planned position. Motion compensation performance of the tracking system was assessed by measurements with radiographic films and a 3D array of 24 ionization chambers. Measurements were performed for stationary detectors and moving detectors using the tracking system. Film measurements showed comparable homogeneity inside the target area. Relative differences of 3D dose distributions within the target volume were 1 +/- 2% with a maximum of 4%. Dose gradients and dose to surrounding areas were in good agreement. The motion tracking system successfully preserved dose distributions delivered to moving targets and maintained target conformity.