A novel algorithm for the calculation of physical and biological irradiation quantities in scanned ion beam therapy: the beamlet superposition approach
TL;DR: A new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements and applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose.
Abstract: The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.
The number of clinical facilities that employ ion therapy to treat cancer is increasing worldwide.
The use of ions different from protons entails the use of more complex irradiation-outcome computation algorithms in treatment planning systems (TPS).
RBE values are usually characterised by big uncertainties (10% or more) and the employment of different radiobiological models by the different centres hinders the comparability of clinical outcomes (Gueulette and Wambersie 2007, Uzawa et al 2009, Steinsträter et al 2012).
As a consequence of the above, there is growing interest in the ion-therapy community for TPS’s capable of dealing with different ion species and of providing a local estimate of the radiobiological effectiveness.
This paper describes the BS model and its application into a treatment planning workflow for spot-scanning (section 2), and provides a demonstration of its capabilities (section 3).
2.1. Principles of the BS model
The BS model allows computing the three-dimensional effect of an ion field incident on a water-like material.
The RBE-weighted dose, which is the absorbed dose multiplied by the corresponding RBE (ICRU Report 85a 2011).
The starting point is the evaluation of the irradiation quantities of a restricted set of small beamlets in water (section 2.2).
It is important to underline that the same beamlets weights are exploited to determine several physical and radiobiological quantities in parallel, not just the dose; this was not considered in the aforementioned superposition models, which were restricted to dose computations.
There are several strategies that can be used to describe the interactions of beamlets with matter.
2.1. Monte Carlo simulations of infinitesimal beamlets.
In some others an explanation in terms of cell survival is not possible (e.g. nausea, fatigue, somnolence, acute edema, resulting from radiation-induced inflammatory cytokines), and even if the LQ parametrisation is still employed to describe the global dose-effect relationship, its use at the local level as outlined in the present model might not be appropriate.
2.3. Modelling the beam optics of a specific beam line
The specificities of a beam line are manifested in its beam optics, that is the evolution of the beam phase space around the isocenter, in the absence of a target.
The longitudinal phase space density is the combination of the energy spread coming from the acceleration and energy-selection systems with the energy spread due to the presence of material on the beam path.
In fact, the Bragg peak produced in a water phantom by a beam that has traversed a passive element corresponding to a thickness ∆z of water-equivalent material can simply be obtained by removing the first ∆z at the phantom entrance from the Bragg peak that the same beam produces without previous interactions.
Depending on the amount of available information on the beam line design, each parameter may be fixed or subjected to vary within a more or less restricted range.
Ideally, the derived beam-line description should be physically meaningful and close to the real set-up in order to be trusted when extrapolating to configurations lacking of experimental characterisation.
2.4. Evaluating the beam irradiation quantities
The computed beam phase space density at the patient’s entrance is used as weight for the superposition of the beamlet irradiation actions.
The WEPL approach allows creating a correspondence between the path length of a particle in a heterogeneous material and its equivalent path length in water.
– WEPLs are attributed to each position along the beam axis, integrating (28). –.
In the BS model, these considerations apply as well to the other computed quantities, so the track-averaged-LET-to-water and dose-averaged-LET-to-water are computed, instead of their ‘to-medium’ counterparts.
3. Results and discussion
The dose computation capabilities of PlanKIT were benchmarked against experimental data and FLUKA and Syngo® simulations, in order to evaluate the correctness of the implementation and provide some confidence in the BS model usage (sections 3.2–3.6).
Five irradiation configurations were considered: single spots, square monoenergetic fields and cubic spreadout Bragg peaks in homogeneous materials, single beams in a simple heterogeneous geometry and a clinical case.
In addition, in section 3.6.3 some computations are presented to show the kind of analysis the BS model allows.
In section 3.1 the operations performed to commission the BS model on the employed beam line are reported.
3.1. Commissioning the BS model for the CNAO facility
The BS model has so far been successfully commissioned to the CNAO and WPE (Westdeutsches Protonentherapiezentrum Essen) beam lines.
For the sake of brevity, here just the results relative to the horizontal beam line located in the treatment room 3 of CNAO are shown.
The longitudinal transfer functions were realised in terms of the WET distribution w(z) of section 2.3.1 and were independent of beam energy, as it is expected from physical considerations.
The extrapolated proton and carbonion beam phase space densities at the vacuum exit window showed the anticipated decrease of spot size and divergence with increasing beam energy.
As for the radiobiological modelling, the same tissue response made available by Syngo® and used for clinical carbon-ion treatment planning at CNAO and HIT was implemented in the PlanKIT LUTs.
3.2. Evaluation of single beams in a homogeneous phantom
Proton and carbon-ion beam spot profiles were measured after the traversal of different thicknesses of water-equivalent material, in order to check the enlargement of beam size with depth.
With the help of IBA-Dosimetry, tests were performed at CNAO to check its reliability with carbon-ion beams, obtaining performances comparable to the ones showed with protons.
This validation is out of the scope of this paper; related measurements will be referred to in the product data sheet.
For protons, the difference between the spot sigmas measured and simulated by PlanKIT was lower than 5% and 0.3 mm in all conditions but at the end of the range with the highest beam energies, where overestimates up to 10% and 0.7 mm were observed.
At low energies the agreement was better than 3%.
3.3. Check of the low-dose contributions
A water phantom (model 41023, PTW-Freiburg) was placed on the treatment table with its entrance face positioned at the isocenter.
Three consecutive measurements were performed for each point and the mean value and standard deviation were computed.
Measuring the dose in the centre of square monoenergetic fields made of evenly spaced spots of equal intensity provides a way to check whether the modelling of the low-dose envelope for a single spot is sufficiently accurate (Sawakuchi et al 2010, Grevillot et al 2011).
Concerning the irradiation with proton fields, the percentage difference between the field size factors measured and evaluated by PlanKIT was lower than 1% for the 78% of the points, lower than 2% for 96% of the points, and lower than 3% for all the points.
3.4. Evaluation of cubic SOBPs in a homogeneous phantom
Cubic SOBPs of different sizes and in-depth positions (listed in table 1) were irradiated in RW3 with both proton and carbon ions, with homogeneous RBE-weighted doses of 2 and 3 Gy (RBE), respectively.
Since the Lynx® output was given in arbitrary units, the integral intensity of each image was normalised to the PlanKIT integral dose at the same depth.
A closer look revealed that the minor ripple was ascribable to a too large computed spot size at high depths.
In contrast, for the two shallower proton SOBPs, and in general for all depths in the phantom smaller than 23 cm, more than 98% of the surface was passing the 3%–3 mm 3D γ-index criteria.
One cannot exclude the eventuality of a concurrent problem in the dose computation algorithm.the authors.
3.5. Evaluation of single beams in a heterogeneous phantom
The authors also tested the BS model performances in the presence of important material heterogeneity.
Monoenergetic beams were directed towards a heterogeneous phantom consisting of four adjacent homogeneous blocks made of different materials.
This is likely arising from small differences between the conversion from Hounsfield numbers to WEPL implemented in PlanKIT and the one from Hounsfield numbers to material properties set in Fluka.
In any case, this discrepancy was found to be of limited relevance when simulating clinical conditions (as shown in section 3.6.2).
All in all, PlanKIT reproduced fairly well the beam perturbation caused by the presence of the material discontinuity, with results comparable to those reported in similar studies (Soukup et al 2005, Grevillot et al 2012).
3.6. Evaluation of a treatment plan
The actual clinical treatment was planned at CNAO with the Syngo® software, using two laterally-opposed carbon-ion beams.
As it is done routinely, the radiosensitivity of brain tissue was attributed to the whole head, using the LEM I with parameters specified in Krämer and Scholz (2000).
It did not prevent the RBE-weighted dose distribution to pass the 3%–3 mm γ-index criteria in more than 98% of the PTV and in more than 99% of the patient volume having a dose greater than 1% of the maximum.
Differences between the physical dose distributions produced by PlanKIT and FLUKA were visible both in the entrance path of the fields and in the PTV.
In order to illustrate the possibilities offered by the BS model, a side-by-side evaluation of RBE and dose-averaged LET distributions following proton and carbon-ion irradiation is presented in figure 8 for the same treatment set-up considered in section 3.6.2.
4. Conclusions
An algorithm for the computation of the physical and biological irradiation action of ion beams, the BS model, has been proposed and successfully implemented.
Since the beamlet irradiation quantities in water are derived from Monte Carlo simulations, the obtained three-dimensional description is more detailed and more flexible compared to the usual analytical approaches: it allows expressing the outcome of the irradiation of different ion species in terms of different quantities, within the same framework.
The BS model also extends the treatment of beam optics.
The comparisons with experimental data and with FLUKA and Syngo® simulations provide high confidence in the model usage, albeit they cannot be considered sufficient to fully validate it for clinical applications.
Besides, the radiobiological modelling must be subjected to further checks, benchmarking the use of LEM in the BS model either against TRiP98 or against in vitro experimental data, along the lines of what done by Krämer et al (2003).
TL;DR: In this paper, a review and discussion of the state of the art for all techniques using prompt-gamma detection to improve the quality assurance in hadrontherapy is presented.
Abstract: Secondary radiation emission induced by nuclear reactions is correlated to the path of ions in matter. Therefore, such penetrating radiation can be used for in vivo control of hadrontherapy treatments, for which the primary beam is absorbed inside the patient. Among secondary radiations, prompt-gamma rays were proposed for real-time verification of ion range. Such a verification is a desired condition to reduce uncertainties in treatment planning. For more than a decade, efforts have been undertaken worldwide to promote prompt-gamma-based devices to be used in clinical conditions. Dedicated cameras are necessary to overcome the challenges of a broad- and high-energy distribution, a large background, high instantaneous count rates, and compatibility constraints with patient irradiation. Several types of prompt-gamma imaging devices have been proposed, that are either physically-collimated or electronically collimated (Compton cameras). Clinical tests are now undergoing. Meanwhile, other methods than direct prompt-gamma imaging were proposed, that are based on specific counting using either time-of-flight or photon energy measurements. In the present article, we make a review and discuss the state of the art for all techniques using prompt-gamma detection to improve the quality assurance in hadrontherapy.
TL;DR: Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements.
Abstract: Introduction Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. Methods and materials The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. Results Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. Conclusion Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing.
TL;DR: The development of fred is reported on, a new MC simulation platform for treatment planning in ion beam therapy that can transport particles through a 3D voxel grid using a class II MC algorithm, and the most refined module is the transport of proton beams in water.
Abstract: Ion beam therapy is a rapidly growing technique for tumor radiation therapy. Ions allow for a high dose deposition in the tumor region, while sparing the surrounding healthy tissue. For this reason, the highest possible accuracy in the calculation of dose and its spatial distribution is required in treatment planning. On one hand, commonly used treatment planning software solutions adopt a simplified beam-body interaction model by remapping pre-calculated dose distributions into a 3D water-equivalent representation of the patient morphology. On the other hand, Monte Carlo (MC) simulations, which explicitly take into account all the details in the interaction of particles with human tissues, are considered to be the most reliable tool to address the complexity of mixed field irradiation in a heterogeneous environment. However, full MC calculations are not routinely used in clinical practice because they typically demand substantial computational resources. Therefore MC simulations are usually only used to check treatment plans for a restricted number of difficult cases. The advent of general-purpose programming GPU cards prompted the development of trimmed-down MC-based dose engines which can significantly reduce the time needed to recalculate a treatment plan with respect to standard MC codes in CPU hardware. In this work, we report on the development of fred, a new MC simulation platform for treatment planning in ion beam therapy. The code can transport particles through a 3D voxel grid using a class II MC algorithm. Both primary and secondary particles are tracked and their energy deposition is scored along the trajectory. Effective models for particle-medium interaction have been implemented, balancing accuracy in dose deposition with computational cost. Currently, the most refined module is the transport of proton beams in water: single pencil beam dose-depth distributions obtained with fred agree with those produced by standard MC codes within 1-2% of the Bragg peak in the therapeutic energy range. A comparison with measurements taken at the CNAO treatment center shows that the lateral dose tails are reproduced within 2% in the field size factor test up to 20 cm. The tracing kernel can run on GPU hardware, achieving 10 million primary [Formula: see text] on a single card. This performance allows one to recalculate a proton treatment plan at 1% of the total particles in just a few minutes.
TL;DR: FRoG, Fast Recalculation on GPU, enables comparative analysis of different models for estimation of physical and biological effective dose in 3D within minutes and in excellent agreement with the gold standard Monte Carlo simulation.
Abstract: Radiotherapy with protons and heavier ions landmarks a novel era in the field of high-precision cancer therapy. To identify patients most benefiting from this technologically demanding therapy, fast assessment of comparative treatment plans utilizing different ion species is urgently needed. Moreover, to overcome uncertainties of actual in-vivo physical dose distribution and biological effects elicited by different radiation qualities, development of a reliable high-throughput algorithm is required. To this end, we engineered a unique graphics processing unit (GPU) based software architecture allowing rapid and robust dose calculation. FRoG, Fast Recalculation on GPU, currently operates with four particle beams available at Heidelberg Ion Beam Therapy center, i.e., raster-scanning proton (1H), helium (4He), carbon (12C) and oxygen ions (16O). FRoG enables comparative analysis of different models for estimation of physical and biological effective dose in 3D within minutes and in excellent agreement with the gold standard Monte Carlo (MC) simulation. This is a crucial step towards development of next-generation patient specific radiotherapy.
TL;DR: In this article, averaged linear energy transfer (LET) is used to express the radiation quality of ion beams, when characterizing the biological effectiveness of hadronic beams, however, averaged LET may be defined in multiple ways, and the chosen definition may impact the resulting reported value.
Abstract: Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be defined in multiple ways, and the chosen definition may impact the resulting reported value. We review averaged LET definitions found in the literature, and quantify which impact using these various definitions have for different reference setups. We recorded the averaged LET definitions used in 354 publications quantifying the relative biological effectiveness (RBE) of hadronic beams, and investigated how these various definitions impact the reported averaged LET using a Monte Carlo particle transport code. We find that the kind of averaged LET being applied is, generally, poorly defined. Some definitions of averaged LET may influence the reported averaged LET values up to an order of magnitude. For publications involving protons, most applied dose averaged LET when reporting RBE. The absence of what target medium is used and what secondary particles are included further contributes to an ill-defined averaged LET. We also found evidence of inconsistent usage of averaged LET definitions when deriving LET-based RBE models. To conclude, due to commonly ill-defined averaged LET and to the inherent problems of LET-based RBE models, averaged LET may only be used as a coarse indicator of radiation quality. We propose a more rigorous way of reporting LET values, and suggest that ideally the entire particle fluence spectra should be recorded and provided for future RBE studies, from which any type of averaged LET (or other quantities) may be inferred.
TL;DR: Radiobiology for the radiologist, Radiobiology in general, Radiology for radiologists as mentioned in this paper, Radiology in the field of radiology, radiology for radiology.
Abstract: Radiobiology for the radiologist , Radiobiology for the radiologist , کتابخانه دیجیتال جندی شاپور اهواز
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"A novel algorithm for the calculati..." refers background in this paper
...Indeed, a transition to a purely exponential survival has been observed in several in vitro cell irradiation studies (Andisheh et al 2013), and citations therein)....
TL;DR: The physics model implemented inside the FLUKA code is briefly described in this paper, with emphasis on hadronic interactions, and examples of the capabilities of the code are presented including basic (thin target) and complex benchmarks.
Abstract: The physics model implemented inside the FLUKA code are briefly described, with emphasis on hadronic interactions. Examples of the capabilities of the code are presented including basic (thin target) and complex benchmarks.
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"A novel algorithm for the calculati..." refers methods in this paper
...The fact of exploiting a flexible and widely-employed Monte Carlo simulation code such as FLUKA (Ferrari et al 2005, Battistoni et al 2007) automatically provides the possibility of dealing with different types of primary particles, gives access to detailed physical information, and includes an…...
TL;DR: A novel code system, TRiP, dedicated to the planning of radiotherapy with energetic ions, in particular 12C, designed to cooperate with three-dimensional active dose shaping devices like the GSI raster scan system is described.
Abstract: We describe a novel code system, TRiP, dedicated to the planning of radiotherapy with energetic ions, in particular 12C. The software is designed to cooperate with three-dimensional active dose shaping devices like the GSI raster scan system. This unique beam delivery system allows us to select any combination from a list of 253 individual beam energies, 7 different beam spot sizes and 15 intensity levels. The software includes a beam model adapted to and verified for carbon ions. Inverse planning techniques are implemented in order to obtain a uniform target dose distribution from clinical input data, i.e. CT images and patient contours. This implies the automatic generation of intensity modulated fields of heavy ions with as many as 40 000 raster points, where each point corresponds to a specific beam position, energy and particle fluence. This set of data is directly passed to the beam delivery and control system. The treatment planning code has been in clinical use since the start of the GSI pilot project in December 1997. Forty-eight patients have been successfully planned and treated.
525 citations
"A novel algorithm for the calculati..." refers methods in this paper
...It consisted of the brain radiosensitivity predicted by the LEM (version I) using the parameters specified in (Krämer and Scholz 2000)....
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...As it is done routinely, the radiosensitivity of brain tissue was attributed to the whole head, using the LEM I with parameters specified in Krämer and Scholz (2000)....
TL;DR: It is concluded that the 3D method provides the greatest flexibility for constructing conformal doses in challenging situations, but that when large numbers of beam ports are available, little advantage may be gained from the additional modulation of intensity in depth.
Abstract: The characteristic Bragg peak of protons or heavy ions provides a good localization of dose in three dimensions. Through their ability to deliver laterally and distally shaped homogenous fields, protons have been shown to be a precise and practical method for delivering highly conformal radiotherapy. However, in an analogous manner to intensity modulation for photons, protons can be used to construct dose distributions through the application of many individually inhomogeneous fields, but with the localization of dose in the Bragg peak providing the possibility of modulating intensity within each field in two or three dimensions. We describe four different methods of intensity modulation for protons and describe how these have been implemented in an existing proton planning system. As a preliminary evaluation of the efficacy of these methods, each has been applied to an example case using a variety of field combinations. Dose-volume histogram analysis of the resulting dose distributions shows that when large numbers of fields are used, all techniques exhibit both good target homogeneity and sparing of neighbouring critical structures, with little difference between the four techniques being discerned. As the number of fields is decreased, however, only a full 3D modulation of individual Bragg peaks can preserve both target coverage and sparing of normal tissues. We conclude that the 3D method provides the greatest flexibility for constructing conformal doses in challenging situations, but that when large numbers of beam ports are available, little advantage may be gained from the additional modulation of intensity in depth.
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