| 1. |
- Böhlen, Till Tobias, et al.
(författare)
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A Monte Carlo-based treatment-planning tool for ion beam therapy
- 2013
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 54, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- Ion beam therapy, as an emerging radiation therapy modality, requires continuous efforts to develop and improve tools for patient treatment planning (TP) and research applications. Dose and fluence computation algorithms using the Monte Carlo (MC) technique have served for decades as reference tools for accurate dose computations for radiotherapy. In this work, a novel MC-based treatment-planning (MCTP) tool for ion beam therapy using the pencil beam scanning technique is presented. It allows single-field and simultaneous multiple-fields optimization for realistic patient treatment conditions and for dosimetric quality assurance for irradiation conditions at state-of-the-art ion beam therapy facilities. It employs iterative procedures that allow for the optimization of absorbed dose and relative biological effectiveness (RBE)-weighted dose using radiobiological input tables generated by external RBE models. Using a re-implementation of the local effect model (LEM), the MCTP tool is able to perform TP studies using ions with atomic numbers Z < 8. Example treatment plans created with the MCTP tool are presented for carbon ions in comparison with a certified analytical treatment-planning system. Furthermore, the usage of the tool to compute and optimize mixed-ion treatment plans, i.e. plans including pencil beams of ions with different atomic numbers, is demonstrated. The tool is aimed for future use in research applications and to support treatment planning at ion beam facilities.
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| 2. |
- Böhlen, Till Tobias, et al.
(författare)
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Benchmarking nuclear models of FLUKA and GEANT4 for carbon ion therapy
- 2010
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 55:19, s. 5833-5847
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Tidskriftsartikel (refereegranskat)abstract
- As carbon ions, at therapeutic energies, penetrate tissue, they undergo inelastic nuclear reactions and give rise to significant yields of secondary fragment fluences. Therefore, an accurate prediction of these fluences resulting from the primary carbon interactions is necessary in the patient's body in order to precisely simulate the spatial dose distribution and the resulting biological effect. In this paper, the performance of nuclear fragmentation models of the Monte Carlo transport codes, FLUKA and GEANT4, in tissue-like media and for an energy regime relevant for therapeutic carbon ions is investigated. The ability of these Monte Carlo codes to reproduce experimental data of charge-changing cross sections and integral and differential yields of secondary charged fragments is evaluated. For the fragment yields, the main focus is on the consideration of experimental approximations and uncertainties such as the energy measurement by time-of-flight. For GEANT4, the hadronic models G4BinaryLightIonReaction and G4QMD are benchmarked together with some recently enhanced de-excitation models. For non-differential quantities, discrepancies of some tens of percent are found for both codes. For differential quantities, even larger deviations are found. Implications of these findings for the therapeutic use of carbon ions are discussed.
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| 3. |
- Böhlen, Till Tobias, et al.
(författare)
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Describing Compton scattering and two-quanta positron annihilation based on Compton profiles : two models suited for the Monte Carlo method
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7, s. P07018-
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Tidskriftsartikel (refereegranskat)abstract
- An accurate description of the basic physics processes of Compton scattering and positron annihilation in matter requires the consideration of atomic shell structure effects and, in specific, the momentum distributions of the atomic electrons. Two algorithms which model Compton scattering and two-quanta positron annihilation at rest accounting for shell structure effects are proposed. Two-quanta positron annihilation is a physics process which is of particular importance for applications such as positron emission tomography (PET). Both models use a detailed description of the processes which incorporate consistently Doppler broadening and binding effects. This together with the relatively low level of complexity of the models makes them particularly suited to be employed by fast sampling methods for Monte Carlo particle transport. Momentum distributions of shell electrons are obtained from parametrized one-electron Compton profiles. For conduction electrons, momentum distributions are derived in the framework of a Fermi gas. The Compton scattering model uses an approach which does not employ any free parameter. In contrast, a few semi-empirical approximations are included for the description of the complex physics of electron-positron annihilation resulting in acollinear photons. Comparisons of the Compton scattering model with simpler approaches illustrate the detailed accounting for shell structure effects. A satisfactory agreement is found for comparisons of both newly-developed models with experimental data.
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| 4. |
- Böhlen, Till Tobias, et al.
(författare)
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Effect of Conventional and Ultrahigh Dose Rate FLASH Irradiations on Preclinical Tumor Models : A Systematic Analysis
- 2023
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Ingår i: International Journal of Radiation Oncology Biology Physics. - 0360-3016. ; 117:4, s. 1007-1017
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Compared with conventional dose rate irradiation (CONV), ultrahigh dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed “FLASH effect”, also depends on the tumor toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study examined the hypothesis of tumor isoefficacy for UHDR versus CONV and aimed to identify potential knowledge gaps to inspire future in vivo studies. Methods and Materials: A systematic literature search identified publications assessing in vivo tumor responses comparing UHDR and CONV. Qualitative and quantitative analyses were performed, including combined analyses of tumor growth and survival data. Results: We identified 66 data sets from 15 publications that compared UHDR and CONV for tumor efficacy. The median number of animals per group was 9 (range 3-15) and the median follow-up period was 30.5 days (range 11-230) after the first irradiation. Tumor growth assays were the predominant model used. Combined statistical analyses of tumor growth and survival data are consistent with UHDR isoefficacy compared with CONV. Only 1 study determined tumor-controlling dose (TCD50) and reported statistically nonsignificant differences. Conclusions: The combined quantitative analyses of tumor responses support the assumption of UHDR isoefficacy compared with CONV. However, the comparisons are primarily based on heterogeneous tumor growth assays with limited numbers of animals and short follow-up, and most studies do not assess long-term tumor control probability. Therefore, the assays may be insensitive in resolving smaller response differences, such as responses of radioresistant tumor subclones. Hence, tumor cure experiments, including additional TCD50 experiments, are needed to confirm the assumption of isoeffectiveness in curative settings.
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| 5. |
- Böhlen, Till Tobias, et al.
(författare)
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FLUKA simulations of the response of tissue-equivalent proportional counters to ion beams for applications in hadron therapy and space
- 2011
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 56:20, s. 6545-6561
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Tidskriftsartikel (refereegranskat)abstract
- For both cancer therapy with protons and ions (hadron therapy) and space radiation environments, the spatial energy deposition patterns of the radiation fields are of importance for quantifying the resulting radiation damage in biological structures. Tissue-equivalent proportional counters (TEPC) are the principal instruments for measuring imparted energy on a microscopic scale and for characterizing energy deposition patterns of radiation. Moreover, the distribution of imparted energy can serve as a complementary quantity to particle fluences of the primary beam and secondary fragments for characterizing a radiation field on a physical basis for radiobiological models. In this work, the Monte Carlo particle transport code FLUKA is used for simulating energy depositions in TEPC by ion beams. The capability of FLUKA in predicting imparted energy and derived quantities, such as lineal energy, for microscopic volumes is evaluated by comparing it with a large set of TEPC measurements for different ion beams with atomic numbers ranging from 1 to 26 and energies from 80 up to 1000 MeV/n. The influence of different physics configurations in the simulation is also discussed. It is demonstrated that FLUKA can simulate energy deposition patterns of ions in TEPC cavities accurately and that it provides an adequate description of the main features of the spectra.
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| 6. |
- Böhlen, Till Tobias, et al.
(författare)
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Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters
- 2012
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 57:23, s. 7983-8004
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainties in determining clinically-used relative biological effectiveness (RBE) values for ion beam therapy carry the risk of absolute and relative misestimations of RBE-weighted doses for clinical scenarios. The present study assesses the consequences of hypothetical misestimations of input parameters to the RBE modelling for carbon ion treatment plans by a variational approach. The impact of the variations on resulting cell survival and RBE values is evaluated as a function of the remaining ion range. In addition, the sensitivity to misestimations in RBE modelling is compared for single fields and two opposed fields using differing optimization criteria. It is demonstrated for single treatment fields that moderate variations (up to ±50%) of representative nominal input parameters for four tumours result mainly in a misestimation of the RBE-weighted dose in the planning target volume (PTV) by a constant factor and only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation quality in the PTV eases the clinical importance of uncertainties in the radiobiological treatment parameters as for such a condition uncertainties tend to result only in a systematic misestimation of RBE-weighted dose in the PTV by a constant factor. Two opposed carbon ion fields with a constant RBE in the PTV are found to result in rather robust conditions. Treatments using two ion species may be used to achieve a constant RBE in the PTV irrespective of the size and depth of the spread-out Bragg peak.
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| 7. |
- Böhlen, Till Tobias, 1982-
(författare)
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Monte Carlo particle transport codes for ion beam therapy treatment planning : Validation, development and applications
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- External radiotherapy with proton and ion beams needs accurate tools for the dosimetric characterization of treatment fields. Monte Carlo (MC) particle transport codes, such as FLUKA and GEANT4, can be a valuable method to increase accuracy of dose calculations and to support various aspects of ion beam therapy (IBT), such as treatment planning and monitoring. One of the prerequisites for such applications is however that the MC codes are able to model reliably and accurately the relevant physics processes. As a first focus of this thesis work, physics models of MC codes with importance for IBT are developed and validated with experimental data. As a result suitable models and code configurations for applications in IBT are established. The accuracy of FLUKA and GEANT4 in describing nuclear fragmentation processes and the production of secondary charged nuclear fragments is investigated for carbon ion therapy. As a complementary approach to evaluate the capability of FLUKA to describe the characteristics of mixed radiation fields created by ion beams, simulated microdosimetric quantities are compared with experimental data. The correct description of microdosimetric quantities is also important when they are used to predict values of relative biological effectiveness (RBE). Furthermore, two models describing Compton scattering and the acollinearity of two-quanta positron annihilation at rest in media were developed, validated and integrated in FLUKA. The detailed description of these processes is important for an accurate simulation of positron emission tomography (PET) and prompt-γ imaging. Both techniques are candidates to be used in clinical routine to monitor dose administration during cancer treatments with IBT. The second objective of this thesis is to contribute to the development of a MC-based treatment planning tool for protons and ions with atomic number Z ≤ 8 using FLUKA. In contrast to previous clinical FLUKA-based MC implementations for IBT which only re-calculate a given treatment plan, the developed prototype features inverse optimization of absorbed dose and RBE-weighted dose for single fields and simultaneous multiple-field optimization for realistic treatment conditions. In a study using this newly-developed tool, the robustness of IBT treatment fields to uncertainties in the prediction of RBE values is investigated, while comparing different optimization strategies.
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| 8. |
- Böhlen, Till Tobias, et al.
(författare)
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Simulations of microdosimetric quantities with the Monte Carlo code FLUKA for carbon ions at therapeutic energies
- 2012
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 88:1-2, s. 176-182
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Microdosimetric quantities can be used to estimate the biological effectiveness of radiation fields. This study evaluates the capability of the general-purpose Monte Carlo code FLUKA to simulate microscopic patterns of energy depositions for mixed radiation fields which are created by carbon ions at therapeutic energies in phantoms. Materials and methods: Measured lineal energy spectra and linear energy transfer (LET) spectra produced by carbon ions of about 300 MeV/n at different depths in phantoms representing human tissue were chosen from published literature and were compared with results from simulations of the measurement set-ups with FLUKA. Results: Simulations of the dose-weighted lineal energy spectra yd(y) and dose-weighted LET spectra describe the main features of the respective measured spectra. All simulated frequency mean and dose mean lineal energy values are, respectively, within 21% and 11% of the measured ones. A slight underestimation of fragment fluences is notable. It is shown that the simultaneous detection of several charged fragments in the TEPC ('V effect') has considerable impact on the measured lineal energy spectra of fragments. Conclusions: Agreement between measurements and FLUKA results is encouraging and shows that FLUKA can predict microdosimetric spectra of mixed radiation fields created by therapeutic carbon ions in phantoms reasonably well.
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| 9. |
- Mairani, A., et al.
(författare)
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A Monte Carlo-based treatment planning tool for proton therapy
- 2012
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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 time. In the present 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 are presented for clinical treatment parameters as used at the CNAO (Italian Center for Hadrontherapy) facility. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios and dosimetric measurements. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.
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| 10. |
- Mairani, A., et al.
(författare)
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A Monte Carlo-based treatment planning tool for proton therapy
- 2013
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 58:8, s. 2471-2490
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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