Reliable treatment planning of highly conformal scanned ion beam therapy demands accurate tools for the determination and characterization of the individual pencil-like beams building up the integral ...dose delivery and related mixed radiation field. At present, clinically practicable inverse treatment planning systems (TPSs) can only rely on fast-performing analytical algorithms. However, the rapidly emerging though more computationally intensive Monte Carlo (MC) methods can be employed to complement analytical TPS, e.g., via accurate calculations of the input beam-model data, together with a considerable reduction of the measuring time. Here we present the work done for the application of the FLUKA MC code to support several aspects of scanned ion beam delivery and treatment planning at the Heidelberg Ion Beam Therapy Center (HIT). Emphasis is given to the generation of the accelerator library and of experimentally validated TPS input basic data which are now in clinical use for proton and carbon ion therapy. Additionally, MC dose calculations of planned treatments in water are shown to represent a valuable tool for supporting treatment plan verification in comparison to dosimetric measurements. This paper can thus provide useful information and guidelines for the start-up and clinical operation of forthcoming ion beam therapy facilities similar to HIT.
Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, 16O ions are being widely discussed due to their increased LET ...distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with 16O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from 20 up to 750 keV μm−1, oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, 16O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to 12C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where 16O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of 0.15% or lower) and relatively low doses ( 4 Gy or lower) the choice of 16O over 12C or 4He may be justified.
Recently, it has been proposed that a mixed helium/carbon beam could be used for online monitoring in carbon ion beam therapy. Fully stripped, the two ion species exhibit approximately the same ...mass/charge ratio and hence could potentially be accelerated simultaneously in a synchrotron to the same energy per nucleon. At the same energy per nucleon, helium ions have about three times the range of carbon ions, which could allow for simultaneous use of the carbon ion beam for treatment and the helium ion beam for imaging. In this work, measurements and simulations of PMMA phantoms as well as anthropomorphic phantoms irradiated sequentially with a helium ion and a carbon ion beam at equal energy per nucleon are presented. The range of the primary helium ion beam and the fragment tail of the carbon ion beam exiting the phantoms were detected using a novel range telescope made of thin plastic scintillator sheets read out by a flat-panel CMOS sensor. A 10:1 carbon to helium mixing ratio is used, generating a helium signal well above the carbon fragment background while adding little to the dose delivered to the patient. The range modulation of a narrow air gap of 1 mm thickness in the PMMA phantom that affects less than a quarter of the particles in a pencil beam were detected, demonstrating the achievable relative sensitivity of the presented method. Using two anthropomorphic pelvis phantoms it is shown that small rotations of the phantom as well as simulated bowel gas movements cause detectable changes in the helium/carbon beam exiting the phantom. The future prospects and limitations of the helium/carbon mixing as well as its technical feasibility are discussed.
The introduction of 'new' ion species in particle therapy needs to be supported by a thorough assessment of their dosimetric properties and by treatment planning comparisons with clinically used ...proton and carbon ion beams. In addition to the latter two ions, helium and oxygen ion beams are foreseen at the Heidelberg Ion Beam Therapy Center (HIT) as potential assets for improving clinical outcomes in the near future. We present in this study a dosimetric validation of a FLUKA-based Monte Carlo treatment planning tool (MCTP) for protons, helium, carbon and oxygen ions for spread-out Bragg peaks in water. The comparisons between the ions show the dosimetric advantages of helium and heavier ion beams in terms of their distal and lateral fall-offs with respect to protons, reducing the lateral size of the region receiving 50% of the planned dose up to 12 mm. However, carbon and oxygen ions showed significant doses beyond the target due to the higher fragmentation tail compared to lighter ions (p and He), up to 25%. The Monte Carlo predictions were found to be in excellent geometrical agreement with the measurements, with deviations below 1 mm for all parameters investigated such as target and lateral size as well as distal fall-offs. Measured and simulated absolute dose values agreed within about 2.5% on the overall dose distributions. The MCTP tool, which supports the usage of multiple state-of-the-art relative biological effectiveness models, will provide a solid engine for treatment planning comparisons at HIT.
Scanned ion pencil beams carry a low-dose envelope which can extend up to several centimeters from the individual beam central axis. Depending on the energy and species of the beam, this halo ...consists mainly of secondary particles produced by nuclear interactions in the target or of particles undergoing multiple Coulomb scattering in the beam line components. This halo is often neglected by single Gaussian beam modeling in current treatment planning systems. One possibility of improving the accuracy of treatment planning is to upgrade the used pencil beam models by adding a description of the low-dose envelope. But at the same time it is crucial to keep the calculation time and the complexity for treatment planning in reasonable limits. As a first approach we measured the lateral beam profiles of scanned proton and carbon ion pencil beams at different energies and depths in water and air at the Heidelberg Ion Beam Therapy Center. Then we tried to describe their beam halo by adding a supplementary Gaussian function to the standard single Gauss modeling which is used at the moment by our treatment planning systems. This analysis helped to identify trends in the parameters describing the lateral beam broadening to support its modeling. Finally, it is shown that the accuracy of treatment planning could be improved by the proposed upgrade of the pencil beam model. In particular, the presented experimental data can be either used directly as input for dose calculation or serve for representative comparison with the results of calculation models such as Monte Carlo simulations for the generation of lateral basic data to be input in upgraded beam models of treatment planning systems.
In the field of radiotherapy, Monte Carlo (MC) particle transport calculations are recognized for their superior accuracy in predicting dose and fluence distributions in patient geometries compared ...to analytical algorithms which are generally used for treatment planning due to their shorter execution times. In this work, a newly developed MC-based treatment planning (MCTP) tool for proton therapy is proposed to support treatment planning studies and research applications. It allows for single-field and simultaneous multiple-field optimization in realistic treatment scenarios and is based on the MC code FLUKA. Relative biological effectiveness (RBE)-weighted dose is optimized either with the common approach using a constant RBE of 1.1 or using a variable RBE according to radiobiological input tables. A validated reimplementation of the local effect model was used in this work to generate radiobiological input tables. Examples of treatment plans in water phantoms and in patient-CT geometries together with an experimental dosimetric validation of the plans are presented for clinical treatment parameters as used at the Italian National Center for Oncological Hadron Therapy. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios against dosimetric measurements and commercial analytical TP calculations. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.
•The Magnum-PSI facility is available for plasma-material interaction studies.•Magnum-PSI is capable to reach relevant plasma parameters for the ITER divertor.•Particle fluxes over 1025 m−2s−1 and ...heat fluxes of up to 50 MW m−2 are obtained.•Particle fluences of up to 1030 particles m−2 have been achieved.•Linear regression and artificial neural network analysis have been applied.
The Magnum-PSI facility is unique in its ability to produce and even exceed the heat and particle fluxes expected in the divertor of a fusion reactor, combined with good access to the plasma-material interaction region for diagnostics and relatively easy sample manipulation. In addition, it is possible to study the effects of transient heat loads on a plasma-facing surface, similar to those expected during so called Edge Localized Modes. By virtue of a newly installed superconducting magnet, Magnum-PSI can now maintain these conditions for hours on end for truly long term tests of candidate plasma facing materials. The electron density and temperature in the plasma beam center as a function of different magnetic fields up to 1.6 T, gas flow and source current are determined: particle fluxes greater than 1025 m−2s−1 and heat fluxes of up to 50 MW m−2 are obtained. Linear regression and artificial neural network analysis have been used to gain insight in the general behavior of plasma conditions as a function of these machine settings. The plasma conditions during transient plasma heat loading have also been determined. These capabilities are now being exploited to reach fluence of up to 1030 particles m−2 at ITER-relevant conditions, equivalent to a significant fraction of the divertor service lifetime for the first time.
This work provides a quantitative assessment of helium ion CT (HeCT) for particle therapy treatment planning. For the first time, HeCT based range prediction accuracy in a heterogeneous tissue ...phantom is presented and compared to single-energy x-ray CT (SECT), dual-energy x-ray CT (DECT) and proton CT (pCT). HeCT and pCT scans were acquired using the US pCT collaboration prototype particle CT scanner at the Heidelberg Ion-Beam Therapy Center. SECT and DECT scans were done with a Siemens Somatom Definition Flash and converted to RSP. A Catphan CTP404 module was used to study the RSP accuracy of HeCT. A custom phantom of 20 cm diameter containing several tissue equivalent plastic cubes was used to assess the spatial resolution of HeCT and compare it to DECT. A clinically realistic heterogeneous tissue phantom was constructed using cranial slices from a pig head placed inside a cylindrical phantom (ø150 mm). A proton beam (84.67 mm range) depth-dose measurement was acquired using a stack of GafchromicTM EBT-XD films in a central dosimetry insert in the phantom. CT scans of the phantom were acquired with each modality, and proton depth-dose estimates were simulated based on the reconstructions. The RSP accuracy of HeCT for the plastic phantom was found to be 0.3 ± 0.1%. The spatial resolution for HeCT of the cube phantom was 5.9 ± 0.4 lp cm
for central, and 7.6 ± 0.8 lp cm
for peripheral cubes, comparable to DECT spatial resolution (7.7 ± 0.3 lp cm
and 7.4 ± 0.2 lp cm
, respectively). For the pig head, HeCT, SECT, DECT and pCT predicted range accuracy was 0.25%, -1.40%, -0.45% and 0.39%, respectively. In this study, HeCT acquired with a prototype system showed potential for particle therapy treatment planning, offering RSP accuracy, spatial resolution, and range prediction accuracy comparable to that achieved with a commercial DECT scanner. Still, technical improvements of HeCT are needed to enable clinical implementation.
In the field of particle therapy helium ion beams could offer an alternative for radiotherapy treatments, owing to their interesting physical and biological properties intermediate between protons ...and carbon ions. We present in this work the comparisons and validations of the Monte Carlo FLUKA code against in-depth dosimetric measurements acquired at the Heidelberg Ion Beam Therapy Center (HIT). Depth dose distributions in water with and without ripple filter, lateral profiles at different depths in water and a spread-out Bragg peak were investigated. After experimentally-driven tuning of the less known initial beam characteristics in vacuum (beam lateral size and momentum spread) and simulation parameters (water ionization potential), comparisons of depth dose distributions were performed between simulations and measurements, which showed overall good agreement with range differences below 0.1 mm and dose-weighted average dose-differences below 2.3% throughout the entire energy range. Comparisons of lateral dose profiles showed differences in full-width-half-maximum lower than 0.7 mm. Measurements of the spread-out Bragg peak indicated differences with simulations below 1% in the high dose regions and 3% in all other regions, with a range difference less than 0.5 mm. Despite the promising results, some discrepancies between simulations and measurements were observed, particularly at high energies. These differences were attributed to an underestimation of dose contributions from secondary particles at large angles, as seen in a triple Gaussian parametrization of the lateral profiles along the depth. However, the results allowed us to validate FLUKA simulations against measurements, confirming its suitability for 4He ion beam modeling in preparation of clinical establishment at HIT. Future activities building on this work will include treatment plan comparisons using validated biological models between proton and helium ions, either within a Monte Carlo treatment planning engine based on the same FLUKA code, or an independent analytical planning system fed with a validated database of inputs calculated with FLUKA.
The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently, the use of NP has been extended to charged particle therapy in order to improve the ...performance in radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in NP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-based Fourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NP-induced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped with AuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon and oxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral regions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellular modifications were detected, such as conformational changes in secondary protein structures, intensity variations in the lipid CH
x
stretching bands, as well as complex DNA rearrangements following charged particle therapy irradiations. These spectral features seem to be correlated with the already shown enhancement both in the DNA damage response and in the reactive oxygen species (ROS) production by the NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational features were NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided new insights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches.
This work provides new insights into the molecular changes in response to nanoparticle-based radiotherapy treatments using ion beams through synchrotron-based infrared microspectroscopy.
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