Optimized treatment planning for prostate cancer comparing IMPT,VHEET and 15 MV IMXT

The merits of intensity-modulated very-high energy electron therapy (VHEET) and intensity-modulated proton therapy (IMPT) in relation to intensity-modulated x-ray therapy (IMXT) with respect to the treatment of the prostate have been quantified. Optimized dose distributions were designed for 5-11 beams of 250 MeV VHEET and 15 MV IMXT as well as 1-9 beam ports of IMPT. In the case of the comparison between 250 MeV VHEET and 15 MV IMXT, it was found that the quality of target coverage achievable with VHEET was comparable to or sometimes better than that provided by IMXT. However, VHEET provided an improvement over IMXT in the dose sparing of the sensitive structures and normal tissues. Compared to IMXT, VHEET decreased the mean rectal dose and bladder dose by up to 10% of the prescribed target dose, while reducing by up to 12% of the prescribed target dose the integral dose to normal tissues. In quantifying the merits of IMPT relative to IMXT, it was found that using intensity-modulated proton beams for inverse planning instead of intensity-modulated photon beams improved target dose homogeneity by up to 1.3% of the prescribed target dose, while reducing the mean rectal dose, bladder dose, and normal tissue integral dose by up to 27%, 30% and 28% of the prescribed target dose respectively. The comparison of optimized planning for IMPT and VHEET showed that the quality of target coverage achievable with IMPT is comparable to or better (by up to 1.3% of the prescribed target dose) than that provided by VHEET. Compared to VHEET, IMPT delivered a mean rectal dose and a bladder dose that was lower by up to 17% and 23% of prescribed target dose respectively, and also reduced the integral dose to normal tissues by up to 17% of the prescribed target dose. These results indicate that of the three modalities the greatest dose escalation will be possible with IMPT, then VHEET, and then IMXT. It follows that IMPT will result in the highest probability of complication-free tumour control, while IMXT will provide the lowest probability.     

A Monte Carlo dose calculation algorithm for proton therapy

A Monte Carlo (MC) code (VMCpro) for treatment planning in proton beam therapy of cancer is introduced. It is based on ideas of the Voxel Monte Carlo algorithm for photons and electrons and is applicable to human tissue for clinical proton energies. In the present paper the implementation of electromagnetic and nuclear interactions is described. They are modeled by a Class II condensed history algorithm with continuous energy loss, ionization, multiple scattering, range straggling, delta-electron transport, nuclear elastic proton nucleus scattering and inelastic proton nucleus reactions. VMCpro is faster than the general purpose MC codes FLUKA by a factor of 13 and GEANT4 by a factor of 35 for simulations in a phantom with inhomogeneities. For dose calculations in patients the speed improvement is larger, because VMCpro has only a weak dependency on the heterogeneity of the calculation grid. Dose distributions produced with VMCpro are in agreement with GEANT4 results. Integrated or broad beam depth dose curves show maximum deviations not larger than 1% or 0.5 mm in regions with large dose gradients for the examples presented here.     

Monte Carlo dose calculations for spot scanned proton therapy

Density heterogeneities can have a profound effect on dose distributions for proton therapy. Although analytical calculations in homogeneous media are relatively straightforward, the modelling of the propagation of the beam through density heterogeneities can be more problematical. At the Paul Scherrer Institute, an in-house dedicated Monte Carlo (MC) code has been used for over a decade to assess the possible deficiencies of the analytical calculations in patient geometries. The MC code has been optimized for speed, and as such traces primary protons only through the treatment nozzle and patient's CT. Contributions from nuclear interactions are modelled analytically with no tracing of secondary particles. The MC code has been verified against measured data in water and experimental proton radiographs through a heterogeneous anthropomorphic phantom. In comparison to the analytical calculation, the MC code has been applied to both spot scanned and intensity modulated proton therapy plans, and to a number of cases containing titanium metal implants. In summary, MC-based dose calculations could provide an invaluable tool for independently verifying the calculated dose distribution within a patient geometry as part of a comprehensive quality assurance protocol for proton treatment plans.     

An efficient dose calculation strategy for intensity modulated proton therapy

While intensity-modulated proton therapy (IMPT) has great potential to improve the therapeutic efficacy of radiotherapy, IMPT optimization can be computationally demanding, particularly for large and complex tumors. Here we propose a dose calculation strategy to accelerate IMPT optimization while reducing memory requirements. By using two adjustable threshold parameters, our method separates dose contributions from proton beamlets into major and minor components for each dose voxel. The optimization proceeds with two levels of iterations: in inner iterations, doses are updated in correspondence with changes in beamlet intensities from only the major contributions while keeping the portions from the minor contributions constant; in outer iterations, doses are recalculated exactly by considering both major and minor contributions. Since the number of elements in the influence matrix for major contributions is relatively small, each inner iteration proceeds quickly. Each outer iteration requires a longer computation time, but only a few such iterations are needed. Our study shows that the proposed strategy leads to nearly identical dose distributions as those optimized with the full influence matrix, but reducing computing time by at least a factor of 3 and internal memory requirements by a factor of 10 or more. In addition, we show that the proposed approach could enhance other optimization-related applications such as optimizing beam angles. By using an advanced lung cancer case that would demand large computing resources by conventional optimization approach, we show how our method may potentially help improve IMPT treatment planning in real clinical situations.     

Intensity-modulated radiation therapy (IMRT) by a dynamic-jaws-only (DJO) technique in rotate-translate mode

In this note it is shown how the use of a rotate-translate methodology employing only jaws, which move dynamically with the beam continuously on, can lead to a delivery of a two-dimensional intensity-modulated beam wherein the modulation is spatially slowly varying. All that is necessary is that a pair of jaws sweep across the face of an accelerator with the aperture between them suitably varying in width and defined by a position-time trajectory function for each jaw. This is then repeated, at the same gantry angle, with the jaws rotated to a different head twist and with a different jaw-pair trajectory for a number of sequential head twists. The result of superposing the individual beams at the same gantry angle is a two-dimensional variation of fluence at this gantry angle. A powerful theorem is developed which shows that there is an infinity of jaw trajectories for some specified number of head twists, each of which corresponds to the same delivered two-dimensional modulated beam.     

Analytic estimates of secondary neutron dose in proton therapy

Proton beam losses in various components of a treatment nozzle generate secondary neutrons, which bring unwanted out of field dose during treatments. The purpose of this study was to develop an analytic method for estimating neutron dose to a distant organ at risk during proton therapy. Based on radiation shielding calculation methods proposed by Sullivan, we developed an analytical model for converting the proton beam losses in the nozzle components and in the treatment volume into the secondary neutron dose at a point of interest. Using the MCNPx Monte Carlo code, we benchmarked the neutron dose rates generated by the proton beam stopped at various media. The Monte Carlo calculations confirmed the validity of the analytical model for simple beam stop geometry. The analytical model was then applied to neutron dose equivalent measurements performed on double scattering and uniform scanning nozzles at the Midwest Proton Radiotherapy Institute (MPRI). Good agreement was obtained between the model predictions and the data measured at MPRI. This work provides a method for estimating analytically the neutron dose equivalent to a distant organ at risk. This method can be used as a tool for optimizing dose delivery techniques in proton therapy.     

A point dose method for in vivo range verification in proton therapy

Range uncertainty in proton therapy is a recognized concern. For certain treatment sites, less optimal beam directions are used to avoid the potential risk, but also with reduced benefit. In vivo dosimetry, with implanted or intra-cavity dosimeters, has been widely used for treatment verification in photon/electron therapy. The method cannot, however, verify the beam range for proton treatment, unless we deliver the treatment in a different manner. Specifically, we split the spread-out Bragg peaks in a proton field into two separate fields, each delivering a 'sloped' depth-dose distribution, rather than the usual plateau in a typical proton field. The two fields are 'sloped' in opposite directions so that the total depth-dose distribution retains the constant dose plateau covering the target volume. By measuring the doses received from both fields and calculating the ratio, the water-equivalent path length to the location of the implanted dosimeter can be verified, thus limiting range uncertainty to only the remaining part of the beam path. Production of such subfields has been experimented with a passive scattering beam delivery system. Phantom measurements have been performed to illustrate the application for in vivo beam range verification.     

Real-time dose calculation and visualization for the proton therapy of ocular tumours

A new real-time dose calculation and visualization was developed as part of the new 3D treatment planning tool OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner Institut Berlin. The implementation resolves the common separation between parameter definition, dose calculation and evaluation and allows a direct examination of the expected dose distribution while adjusting the treatment parameters. The new tool allows the therapist to move the desired dose distribution under visual control in 3D to the appropriate place. The visualization of the resulting dose distribution as a 3D surface model, on any 2D slice or on the surface of specified ocular structures is done automatically when adapting parameters during the planning process. In addition, approximate dose volume histograms may be calculated with little extra time. The dose distribution is calculated and visualized in 200 ms with an accuracy of 6% for the 3D isodose surfaces and 8% for other objects. This paper discusses the advantages and limitations of this new approach.     

Efficient voxel navigation for proton therapy dose calculation in TOPAS and Geant4

A key task within all Monte Carlo particle transport codes is 'navigation', the calculation to determine at each particle step what volume the particle may be leaving and what volume the particle may be entering. Navigation should be optimized to the specific geometry at hand. For patient dose calculation, this geometry generally involves voxelized computed tomography (CT) data. We investigated the efficiency of navigation algorithms on currently available voxel geometry parameterizations in the Monte Carlo simulation package Geant4: G4VPVParameterisation, G4VNestedParameterisation and G4PhantomParameterisation, the last with and without boundary skipping, a method where neighboring voxels with the same Hounsfield unit are combined into one larger voxel. A fourth parameterization approach (MGHParameterization), developed in-house before the latter two parameterizations became available in Geant4, was also included in this study. All simulations were performed using TOPAS, a tool for particle simulations layered on top of Geant4. Runtime comparisons were made on three distinct patient CT data sets: a head and neck, a liver and a prostate patient. We included an additional version of these three patients where all voxels, including the air voxels outside of the patient, were uniformly set to water in the runtime study. The G4VPVParameterisation offers two optimization options. One option has a 60-150 times slower simulation speed. The other is compatible in speed but requires 15-19 times more memory compared to the other parameterizations. We found the average CPU time used for the simulation relative to G4VNestedParameterisation to be 1.014 for G4PhantomParameterisation without boundary skipping and 1.015 for MGHParameterization. The average runtime ratio for G4PhantomParameterisation with and without boundary skipping for our heterogeneous data was equal to 0.97: 1. The calculated dose distributions agreed with the reference distribution for all but the G4PhantomParameterisation with boundary skipping for the head and neck patient. The maximum memory usage ranged from 0.8 to 1.8 GB depending on the CT volume independent of parameterizations, except for the 15-19 times greater memory usage with the G4VPVParameterisation when using the option with a higher simulation speed. The G4VNestedParameterisation was selected as the preferred choice for the patient geometries and treatment plans studied.     

Three-dimensional dose verification with x-ray films in conformal carbon ion therapy

A three-dimensional dose verification with photographic emulsions (x-ray films) was realized within the tumour therapy project at GSI Darmstadt, using carbon ions. We present Bragg-peak measurements for 88, 100 and 200 MeV/u carbon ion beams as the simplest case of dose verification. An actual patient treatment plan, composed by the superposition of Bragg-peaks having different energies and intensities, was used to perform a three-dimensional dose verification of an irregularly formed target volume. The shape of the measured dose distribution from film closely matches the intended irradiation volume. Furthermore, the calculated and measured optical density distribution is in good agreement with a maximum deviation of less than 10%.     

一种新型质子治疗剂量递送系统的设计研究及模拟验证

目的:针对激光等离子体加速的质子束流特性,设计用于剂量递送的新型紧凑治疗头系统,并通过模拟计算验证该方法的有效性与适用性。方法:基于实验上已实现的激光质子束流参数,利用散射体设计软件NEU（Nozzles with Everything Upstream）进行流线型散射体设计。通过散角选择和能散调制进一步优化剂量递送效率,并利用蒙特卡罗模拟计算软件TOPAS（TOol for PArticle Simulation）及底层的Geant4（GEometry ANd Tracking）计算引擎分析并验证激光质子通过此剂量递送方法后水模体中的剂量分布。结果:在直径6 cm、高5 cm的圆柱形靶区内,深度剂量分布平坦度在±1%以内,横向剂量分布在±3%以内。结论:此剂量递送方法及系统适用于现阶段激光质子束流特性,水模体靶区内剂量递送均匀、高效且稳定。     

Sensitivity of different dose scoring methods on organ-specific neutron dose calculations in proton therapy

Scattered doses, e.g. neutron doses in proton therapy, are of concern in radiation therapy. Although measured data are the gold standard, Monte Carlo simulations allow a more realistic consideration of patient anatomy via whole-body phantoms. When calculating neutron doses with Monte Carlo techniques, the dose can be scored in different ways because neutrons deposit dose indirectly. The purpose of this study was to assess the differences in neutron dose predictions when using different dose scoring methods. Two methods were tested. In the first method, the organ dose was calculated by accumulating dose from each individual dose deposition event with a particle-specific radiation weighting factor applied. Alternatively, we applied a method where the calculation was done by averaging the dose over the total number of events irrespective of particle type and applying average neutron radiation weighting factors. In addition, we assessed the sensitivity of different neutron quality factor assignments based on two recommendations by the International Commission on Radiological Protection (ICRP). We found that the scoring procedure can lead to differences in the organ equivalent dose of about 25%. As to the ICRP definition of neutron quality factors, the most recent recommendation results in about 10% higher organ doses.     

Out-of-field dose equivalents delivered by proton therapy of prostate cancer

Measurements were performed to assess the dose equivalent outside a primary proton treatment field, using a silicon-on-insulator (SOI) microdosimeter. The SOI microdosimeter was placed on the surface of an anthropomorphic phantom and dose equivalents were determined as a function of lateral distance from a typical passively scattered and modulated prostate treatment field. Measurements were also completed within a polystyrene plate phantom as a function of depth for a distance of 5 cm from the field edge, as function of lateral distance from field edge at two different depths, and as a function of distance from the distal edge on the central beam axis. The dose equivalent at the surface of the anthropomorphic phantom decreases from 3.9 to 0.18 mSv/Gy when the lateral distance from the proton field edge increases from 2.5 to 60 cm. Measurements along the proton depth dose distribution at a constant distance of 5 cm from the primary field edge indicate a decrease in dose equivalent as a function of depth, with a 38% decrease relative to the surface dose at a depth of 5 cm in polystyrene. Measurements completed as a function of lateral distance from the primary field at two separate depths within polystyrene illustrate a convergence of the dose equivalent at approximately 20 cm from the primary field edge. Past the distal edge of the spread-out Bragg peak dose equivalents decrease exponentially for increasing distance, with an initial value of 1.6 mSv/Gy at 0.6 cm from the distal edge. Silicon microdosimetry measurements were also compared with published results obtained utilizing different measurement techniques. This study demonstrates the applicability of SOI microdosimetry in determining the dose equivalent outside proton treatment fields, and provides valuable information on the dose equivalent both at the surface and at depth experienced by prostate cancer patients treated with protons.     

The basic study of a bi-material range compensator for improving dose uniformity for proton therapy

A range compensator (abbreviated as a RC hereafter) is used to form a conformal dose distribution for heavy-charged-particle therapy. However, it induces distortion of the dose distribution. The induced inhomogeneity may result in a calibration error of a monitor unit (MU) assigned to a transmission ionization chamber. By using a bi-material RC made from a low-Z material and a high-Z material instead of the regular RC, the dose inhomogeneity has been obviously reduced by equalizing the lateral dose distributions formed by pencil beams traversing elements of the RC with different base thicknesses at the same water-equivalent depth. We designed and manufactured a 4 x 4 matrix-shaped single-material RC and a bi-material RC with the same range losses at corresponding elements of the RCs. The bi-material RC is made from chemical wood (the main chemical component is an ABS resin) as a low-Z material and from brass as a high-Z material. Sixteen segments of the RC are designed so that the range-loss differences of the adjacent segments of the RC range from 0 to 50 mm in steps of 5 mm. We measured dose distributions in water formed by a 160 MeV proton beam traversing the single-material RC or the bi-material RC, using the HIMAC biology beam port. Large dips and bumps were observed in the dose distribution formed by the use of the single-material RC; the dose uniformity has been significantly improved in the target region by the use of the bi-material RC. The improvement has been obtained at the expense of blurring lateral penumbra. For clinical application of this method to a patient with large density inhomogeneity, a simple modification method of the original calculation model has been given.     

Calculations of neutron dose equivalent exposures from range-modulated proton therapy beams

Passive beam spreading techniques have been used for most proton therapy treatments worldwide. This delivery method employs static scattering foils to spread the beam laterally and a range modulating wheel or ridge filter to spread the high dose region in depth to provide a uniform radiation dose to the treatment volume. Neutrons produced by interactions of the treatment beam with nozzle components, such as the range modulation wheel, can account for a large portion of the secondary dose delivered to healthy tissue outside the treatment volume. Despite this fact, little is known about the effects of range modulation on the secondary neutron exposures around passively scattered proton treatment nozzles. In this work, the neutron dose equivalent spectra per incident proton (H(E)/p) and total neutron dose equivalent per therapeutic absorbed dose (H/D) were studied using Monte Carlo techniques for various values of range modulation at 54 locations around a passive scattering proton therapy treatment nozzle. As the range modulator wheel step thickness increased from 1.0 to 11.5 cm, the peak values of H(E)/p decreased from approximately 1 x 10(-17) mSv Gy(-1) to approximately 2 x 10(-18) mSv Gy(-1) at 50 cm from isocentre along the beam's central axis. In general, H/D increased with increasing range modulation at all locations studied, and the maximum H/D exposures shifted away from isocentre.     

Feasibility of MRI guided proton therapy: magnetic field dose effects

Many methods exist to improve treatment outcome in radiotherapy. Two of these are image-guided radiotherapy (IGRT) and proton therapy. IGRT aims at a more precise delivery of the radiation, while proton therapy is able to achieve more conformal dose distributions. In order to maximally exploit the sharp dose gradients from proton therapy it has to be combined with soft-tissue based IGRT. MRI-guided photon therapy (currently under development) offers unequalled soft-tissue contrast and real-time image guidance. A hybrid MRI proton therapy system would combine these advantages with the advantageous dose steering capacity of proton therapy. This paper addresses a first technical feasibility issue of this concept, namely the impact of a 0.5 T magnetic field on the dose distribution from a 90 MeV proton beam. In contrast to photon therapy, for MR-guided proton therapy the impact of the magnetic field on the dose distribution is very small. At tissue-air interfaces no effect of the magnetic field on the dose distribution can be detected. This is due to the low-energy of the secondary electrons released by the heavy protons.     

Some optimum conditions for proton induced ultrasoft x-ray production

The proton beam from an AN700 van de Graaff accelerator has been used to bombard solid targets of C, TiB2, SiC, SiN, Al and Au in the energy range 250-700 keV. A study of target surface contamination, the nature of the angular dependence in the x-ray emission and the dependence of the x-ray yield on proton energy has been undertaken. Our findings suggest that the optimum target angle is 30 degrees with respect to the incident proton direction and the detector angle 90 degrees to the target surface. In a vacuum of 10(-5) Torr (approximately 1.33 mPa) and at proton currents of 50-100 muA, a carbon deposit can be expected to build up with time on the target surface to reduce the characteristic x-ray intensity from the target. In the comparison between the energy dependent yields of CK and AlK x-rays, we find a slightly smaller dependence on energy than that predicted by the empirical cross section formula of Paul (1984) although the latter is not expected to be valid down to Z = 6.