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Magnetic resonance guidance in particle therapy has the potential to improve the current performance of clinical workflows. However, the presence of magnetic fields challenges the current algorithms for treatment planning. To ensure proper dose calculations, compensation methods are required to guarantee that the maximum deposited energy of deflected beams lies in the target volume. In addition, proper modifications of the intrinsic dose calculation engines, accounting for magnetic fields, are needed. In this work, an algorithm for proton treatment planning in magnetic fields was implemented in a research treatment planning system (TPS), matRad. Setup-specific look up tables were generated using a validated MC model for a clinical proton beamline (62.4 - 215.7 MeV) interacting with a dipole magnet (B = 0-1 T). The algorithm was successfully benchmarked against MC simulations in water, showing gamma index (2%/2mm) global pass rates higher than 96% for different plan configurations. Additionally, absorbed depth doses were compared with experimental measurements in water. Differences within 2% and 3.5% in the Bragg peak and entrance regions, respectively, were found. Finally, treatment plans were generated and optimized for magnetic field strengths of 0 and 1 T to assess the performance of the proposed model. Equivalent treatment plans and dose volume histograms were achieved, independently of the magnetic field strength. Differences lower than 1.5% for plan quality indicators (D 2% , D 50% , D 90% , V 95% and V 105% ) in water, a TG119 phantom and an exemplary prostate patient case were obtained. More complex treatment planning studies are foreseen to establish the limits of applicability of the proposed model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Magnetic resonance guidance in proton therapy (MRPT) is expected to improve its current performance. The combination of magnetic fields with clinical proton beam lines poses several challenges for dosimetry, treatment planning and dose delivery. Proton beams are deflected by magnetic fields causing considerable changes in beam trajectories and also a retraction of the Bragg peak positions. A proper prediction and compensation of these effects is essential to ensure accurate dose calculations. This work aims to develop and benchmark a Monte Carlo (MC) beam model for dose calculation of MRPT for static magnetic fields up to 1 T., Methods: Proton beam interactions with magnetic fields were simulated using the GATE/Geant4 toolkit. The transport of charged particle in custom 3D magnetic field maps was implemented for the first time in GATE. Validation experiments were done using a horizontal proton pencil beam scanning system with energies between 62.4 and 252.7 MeV and a large gap dipole magnet (B = 0-1 T), positioned at the isocenter and creating magnetic fields transverse to the beam direction. Dose was measured with Gafchromic EBT3 films within a homogeneous PMMA phantom without and with bone and tissue equivalent material slab inserts. Linear energy transfer (LET) quenching of EBT3 films was corrected using a linear model on dose-averaged LET method to ensure a realistic dosimetric comparison between simulations and experiments. Planar dose distributions were measured with the films in two different configurations: parallel and transverse to the beam direction using single energy fields and spread-out Bragg peaks. The MC model was benchmarked against lateral deflections and spot sizes in air of single beams measured with a Lynx PT detector, as well as dose distributions using EBT3 films. Experimental and calculated dose distributions were compared to test the accuracy of the model., Results: Measured proton beam deflections in air at distances of 465, 665, and 1155 mm behind the isocenter after passing the magnetic field region agreed with MC-predicted values within 4 mm. Differences between calculated and measured beam full width at half maximum (FWHM) were lower than 2 mm. For the homogeneous phantom, measured and simulated in-depth dose profiles showed range and average dose differences below 0.2 mm and 1.2%, respectively. Simulated central beam positions and widths differed <1 mm to the measurements with films. For both heterogenous phantoms, differences within 1 mm between measured and simulated central beam positions and widths were obtained, confirming a good agreement of the MC model., Conclusions: A GATE/Geant4 beam model for protons interacting with magnetic fields up to 1 T was developed and benchmarked to experimental data. For the first time, the GATE/Geant4 model was successfully validated not only for single energy beams, but for SOBP, in homogeneous and heterogeneous phantoms. EBT3 film dosimetry demonstrated to be a powerful dosimetric tool, once the film response function is LET corrected, for measurements in-line and transverse to the beam direction in magnetic fields. The proposed MC beam model is foreseen to support treatment planning and quality assurance (QA) activities toward MRPT., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: The dose core of a proton pencil beam (PB) is enveloped by a low dose area reaching several centimeters off the central axis and containing a considerable amount of the dose. Adequate modeling of the different components of the PB profile is, therefore, required for accurate dose calculation. In this study, we experimentally validated one electromagnetic and two nuclear scattering models in GATE/Geant4 for dose calculation of proton beams in the therapeutic energy window (62-252 MeV) with and without range shifter (RaShi)., Methods: The multiple Coulomb scattering (MCS) model was validated by lateral dose core profiles measured for five energies at up to four depths from beam plateau to Bragg peak region. Nuclear halo profiles of single PBs were evaluated for three (62.4, 148.2, and 252.7 MeV) and two (97.4 and 124.7 MeV) energies, without and with RaShi, respectively. The influence of the dose core and nuclear halo on field sizes varying from 2-20 cm was evaluated by means of output factors (OFs), namely frame factors (FFs) and field size factors (FSFs), to quantify the relative increase of dose when increasing the field size., Results: The relative increase in the dose core width in the simulations deviated negligibly from measurements for depths until 80% of the beam range, but was overestimated by up to 0.2 mm in σ toward the end of range for all energies. The dose halo region of the lateral dose profile agreed well with measurements in the open beam configuration, but was notably overestimated in the deepest measurement plane of the highest energy or when the beam passed through the RaShi. The root-mean-square deviations (RMSDs) between the simulated and the measured FSFs were less than 1% at all depths, but were higher in the second half of the beam range as compared to the first half or when traversing the RaShi. The deviations in one of the two tested hadron physics lists originated mostly in elastic scattering. The RMSDs could be reduced by approximately a factor of two by exchanging the default elastic scattering cross sections for protons., Conclusions: GATE/Geant4 agreed satisfyingly with most measured quantities. MCS was systematically overestimated toward the end of the beam range. Contributions from nuclear scattering were overestimated when the beam traversed the RaShi or at the depths close to the end of the beam range without RaShi. Both, field size effects and calculation uncertainties, increased when the beam traversed the RaShi. Measured field size effects were almost negligible for beams up to medium energy and were highest for the highest energy beam without RaShi, but vice versa when traversing the RaShi., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

While Monte Carlo (MC) codes are considered as the gold standard for dosimetric calculations, the availability of user friendly MC codes suited for particle therapy is limited. Based on the FLUKA MC code and its graphical user interface (GUI) Flair, we developed an easy-to-use tool which enables simple and reliable simulations for particle therapy. In this paper we provide an overview of functionalities of the tool and with the presented clinical, proton and carbon ion therapy examples we demonstrate its reliability and the usability in the clinical environment and show its flexibility for research purposes. The first, easy-to-use FLUKA MC platform for particle therapy with GUI functionalities allows a user with a minimal effort and reduced knowledge about MC details to apply MC at their facility and is expected to enhance the popularity of the MC for both research and clinical quality assurance and commissioning purposes.

Oxygen ([Formula: see text]) ions are a potential alternative to carbon ions in ion beam therapy. Their enhanced linear energy transfer indicates a higher relative biological effectiveness and a reduced oxygen enhancement ratio. Due to the limited availability of [Formula: see text] ion beams, Monte Carlo (MC) transport codes are important research tools for investigating their potential. The purpose of this study was to validate GATE/Geant4 for [Formula: see text] ion beam therapy using experimental data from literature. Five hadron physics lists and two electromagnetic options were benchmarked against measured depth dose distributions (DDDs) and charge-changing cross sections. The simulated beam ranges deviated by less than 0.5% for all physics configurations and only a few points exceeded the gamma index criterion (2%/1 mm). However, the simulated partial charge-changing cross sections deviated considerably for some hadron physics configurations. Best agreement with the experimental values was obtained with the quantum molecular dynamics model (QMD), and we therefore suggest using this model in Geant4 to accurately describe the fragmentation of [Formula: see text] ion beams into lighter fragments ([Formula: see text]).

Purpose: Comparison of the dosimetric accuracy of the enhanced collapsed cone (eCC) algorithm with the commercially available Monte Carlo (MC) dose calculation for complex treatment techniques., Material and Methods: A total of 8 intensity-modulated radiotherapy (IMRT) and 2 stereotactic body radiotherapy (SBRT) lung cases were calculated with eCC and MC algorithms with the treatment planning systems (TPS) Oncentra MasterPlan 3.2 (Nucletron) and Monaco 2.01 (Elekta/CMS). Fluence optimization as well as sequencing of IMRT plans was primarily performed using Monaco. Dose prediction errors were calculated using MC as reference. The dose-volume histrogram (DVH) analysis was complemented with 2D and 3D gamma evaluation. Both algorithms were compared to measurements using the Delta4 system (Scandidos)., Results: Recalculated with eCC IMRT plans resulted in lower planned target volume (PTV) coverage, as well as in lower organs-at-risk (OAR) doses up to 8%. Small deviations between MC and eCC in PTV dose (1-2%) were detected for IMRT cases, while larger deviations were observed for SBRT (up to 5%). Conformity indices of both calculations were similar; however, the homogeneity of the eCC calculated plans was slightly better. Delta4 measurements confirmed high dosimetric accuracy of both TPS., Conclusion: Mean dose prediction errors < 3% for PTV suggest that both algorithms enable highly accurate dose calculations under clinical conditions. However, users should be aware of slightly underestimated OAR doses using the eCC algorithm.

A Monte Carlo model of an Elekta Precise linear accelerator has been built and verified by measured data for a 6 and 10 MV photon beam running with and without a flattening filter in the beam line. In this study the flattening filter was replaced with a 6 mm thick copper plate, provided by the linac vendor, in order to stabilize the beam. Several studies have shown that removal of the filter improves some properties of the photon beam, which could be beneficial for radiotherapy treatments. The investigated characteristics of this new beam included output, spectra, mean energy, half value layer and the origin of scattered photons. The results showed an increased dose output per initial electron at the central axis of 1.76 and 2.66 for the 6 and 10 MV beams, respectively. The number of scattered photons from the accelerator head was reduced by (31.7 ± 0.03)% (1 SD) for the 6 MV beam and (47.6 ± 0.02)% for the 10 MV beam. The photon energy spectrum of the unflattened beam was softer compared to a conventional beam and did not vary significantly with the off-axis distance, even for the largest field size (0-20 cm off-axis).

The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (gamma) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% +/- 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 x 10 cm(2) field at the first density interface from tissue to lung equivalent material. Small fields (2 x 2 cm(2)) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% +/- 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D gamma-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for gamma(>1) was 4.7% +/- 3.7%, the average gamma(1%) value was 1.19 +/- 0.16 and the mean 2D gamma-value was 0.44 +/- 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

Background: Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high‐spatial‐resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. Purpose: The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. Methods: The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron‐doped CVD diamond. The cross‐section of the sensitive volume of the dosimetric element is 4 mm2 and 1 μm‐thick, while the microdosimetric one has an active cross‐sectional area of 100 × 100 μm2 and a thickness of about 6.2 μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7 MeV/u and proton beam of 148.7 MeV. The particle flux in the region of the microdosimeter was 6·107 cm2/s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE‐Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Results: Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2 keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. Conclusions: The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation. [ABSTRACT FROM AUTHOR]

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others. [ABSTRACT FROM AUTHOR]

The aim of this work is to present the first microdosimetric spectra measured with a miniaturised tissue-equivalent proportional counter in the clinical environment of the MedAustron ion-beam therapy facility. These spectra were gathered with a 62.4-MeV proton beam and have been compared with microdosimetric spectra measured in the 62-MeV clinical proton beam of the CATANA beam line. Monte Carlo simulations were performed using the Geant4 toolkit GATE and a fully commissioned clinical beam line model. Finally, similarities and discrepancies of the measured data to simulations based on a simple and complex detector geometry are discussed. [ABSTRACT FROM AUTHOR]

Background: The increasing number of studies dealing with linear energy transfer (LET)-based evaluation and optimization in the field of carbon ion radiotherapy (CIRT) indicates the rising demand for LET implementation in commercial treatment planning systems (TPS). Benchmarking studies could play a key role in detecting (and thus preventing) computation errors prior implementing such functionalities in a TPS. Purpose: This in silico study was conducted to benchmark the following two LET-related functionalities in a commercial TPS against Monte Carlo simulations: (1) dose averaged LET (LETd) scoring and (2) physical dose filtration based on LET for future LET-based treatment plan evaluation and optimization studies. Methods: The LETd scoring and LET-based dose filtering (in which the deposited dose can be separated into the dose below and above the user specified LET threshold) functionalities for carbon ions in the research version RayStation (RS) 9A-IonPG TPS (RaySearch Laboratories, Sweden) were benchmarked against GATE/Geant4 simulations. Pristine Bragg peaks (BPs) and cuboid targets, positioned at different depths in a homogeneous water phantom and a setup with heterogeneity were used for this study. Results: For all setups (homogeneous and heterogeneous), the mean absolute (and relative) LETd difference was less than 1 keV/μm (3.5%) in the plateau and target and less than 2 keV/μm (8.3%) in the fragmentation tail. The maximum local differences were 4 and 6 keV/μm, respectively. The mean absolute (and relative) physical dose differences for both low- and high-LET doses were less than 1 cGy (1.5%) in the plateau, target and tail with a maximum absolute difference of 2 cGy. Conclusions: No computation error was found in the tested functionalities except for LETd in lateral direction outside the target, showing the limitation of the implemented monochrome model in the tested TPS version. [ABSTRACT FROM AUTHOR]

Purpose: The Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline‐specific look‐up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes. Methods: The particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1‐mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE‐RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re‐computed using the two other fluence tables (FLUKA PhS or Geant4). Results: The fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep‐seated targets. The patient and water phantom cases demonstrated similar results. Conclusion: RBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE‐RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy. [ABSTRACT FROM AUTHOR]

Purpose: To design and commission a water phantom suitable for constrained environments and magnetic fields for magnetic resonance (MR)‐guided proton therapy. Methods: A phantom was designed, to enable precise, remote controlled detector positioning in water within the constrained environment of a magnet for MR‐guided proton therapy. The phantom consists of a PMMA enclosure whose outer dimensions of 81×40×12.5cm3 were chosen to optimize space usage inside the 13.5‐cm bore gap of the magnet. The moving mechanism is based on a low‐height H‐shaped non‐ferromagnetic belt drive, driven by stepper motors located outside of the magnetic field. The control system and the associated electronics were designed in house, with similar features as available in commercial water phantoms. Reproducibility as well as accuracy of the phantom positioning were tested using a high‐precision Leica AT 402 laser tracker. Laterally integrated depth dose curves and lateral beam profiles at three depths were acquired repeatedly for a 148.2 MeV proton beam in water. Results: The phantom was successfully operated with and without applied magnetic fields. For complex movements, a positioning uncertainty within 0.16 mm was found with an absolute accuracy typically below 0.3 mm. Laterally integrated depth dose curves agreed within 0.1 mm with data taken using a commercial water phantom. The lateral beam offset determined from beam profile measurements agreed well with data from Monte Carlo simulations. Conclusion: The phantom is optimally suited for detector positioning and dosimetric experiments within constrained environments in high magnetic fields. [ABSTRACT FROM AUTHOR]

A newly-designed large-area plane-parallel ionization chamber (of type PTW 34089), denoted BPC150, with a nominal active volume diameter of 147 mm is characterized in this study. Such chambers exhibit benefits compared to smaller chambers in the field of scanned light-ion beam dosimetry because they capture a larger fraction of the laterally-spread beam fragments and ease positioning with respect to small fields. The chamber was characterized in 60Co, 200 kV x-ray, proton and carbon ion beams. The chamber-specific beam-quality correction factor kQ,Q0 was determined. To investigate the homogeneity of the chamber's response, a radial response map was acquired. An edge correction was applied when the proton beam only partly impinged on the chamber's active surface. The measured response map showed that the response in the chamber's center is 3% lower than the average response over the total active area. Furthermore, percentage depth dose (PDD) curves in carbon ions were acquired and compared to those obtained with smaller-diameter chambers (i.e. 81.6 mm and 39.6 mm) as well as with results from Monte Carlo simulations. The measured absorbed dose to water cross calibration coefficients resulted in a kQ,Q0 of 0.981 ± 0.020. Regarding carbon ion PDD curves, relative differences between the BPC150 and smaller chambers were observed, especially for higher energies and in the fragmentation tail. These differences reached 10%–22% in the fragmentation tail (compared to the 81.6 mm diameter chamber). Differences increased when comparing to a chamber with 39.6 mm diameter. The provided results characterize the BPC150 thoroughly for usage in scanned light-ion beam dosimetry and demonstrate its advantage of capturing a larger fraction of the laterally-integrated dose in the fragmentation tail. [ABSTRACT FROM AUTHOR]

Purpose: A relative biological effectiveness (RBE) of 1.1 is commonly used in clinical proton therapy, irrespective of tissue type and depth. This in vitro study was conducted to quantify the RBE of scanned protons as a function of the dose‐averaged linear energy transfer (LETd) and the sensitivity factor (α/ß)X. Additionally, three phenomenological models (McNamara, Rørvik, and Jones) and one mechanistic model (repair‐misrepair‐fixation, RMF) were applied to the experimentally derived data. Methods: Four human cell lines (FaDu, HaCat, Du145, SKMel) with differential (α/ß)X ratios were irradiated in a custom‐designed irradiation setup with doses between 0 and 6 Gy at proximal, central, and distal positions of a 80 mm spread‐out Bragg peak (SOBP) centered at 80 mm (setup A: proton energies 66.5–135.6 MeV) and 155 mm (setup B: proton energies 127.2–185.9 MeV) depth, respectively. LETd values at the respective cell positions were derived from Monte Carlo simulations performed with the treatment planning system (TPS, RayStation). Dosimetric measurements were conducted to verify dose homogeneity and dose delivery accuracy. RBE values were derived for doses that resulted in 90 % (RBE90) and 10 % (RBE10) of cell survival, and survival after a 0.5 Gy dose (RBE0.5Gy), 2 Gy dose (RBE2Gy), and 6 Gy dose (RBE6Gy). Results: LETd values at sample positions were 1.9, 2.1, 2.5, 2.8, 4.1, and 4.5 keV/µm. For the cell lines with high (α/ß)X ratios (FaDu, HaCat), the LETd did not impact on the RBE. For low (α/ß)X cell lines (Du145, SKMel), LQ‐derived survival curves indicated a clear correlation of LETd and RBE. RBE90 values up to 2.9 and RBE10 values between 1.4 and 1.8 were obtained. Model‐derived RBE predictions slightly overestimated the RBE for the high (α/ß)X cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (α/ß)X cell lines, no agreement was found between experiments and model predictions, that is, all models underestimated the measured RBE. Conclusions: The sensitivity parameter (α/ß)X was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LETd changes. RBE prediction models are applicable for high (α/ß)X cell lines but do not estimate RBE values with sufficient accuracy in low (α/ß)X cell lines. [ABSTRACT FROM AUTHOR]

Purpose: The dose response of Gafchromic EBT3 films exposed to proton beams depends on the dose, and additionally on the beam quality, which is often quantified with the linear energy transfer (LET) and, hence, also referred to as LET quenching. Fundamentally different methods to determine correction factors for this LET quenching effect have been reported in literature and a new method using the local proton fluence distribution differential in LET is presented. This method was exploited to investigate whether a more practical correction based on the dose‐ or fluence‐averaged LET is feasible in a variety of clinically possible beam arrangements. Methods: The relative effectiveness (RE) was characterized within a high LET spread‐out Bragg peak (SOBP) in water made up by the six lowest available energies (62.4–67.5 MeV, configuration "b1") resulting in one of the highest clinically feasible dose‐averaged LET distributions. Additionally, two beams were measured where a low LET proton beam (252.7 MeV) was superimposed on "b1", which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration "b2" and "b3," respectively. The proton LET spectrum was simulated with GATE/Geant4 at all measurement positions. The net optical density change differential in LET was integrated over the local proton spectrum to calculate the net optical density and therefrom the beam quality correction factor. The LET dependence of the film response was accounted for by an LET dependence of one of the three parameters in the calibration function and was determined from inverse optimization using measurement "b1." This method was then validated on the measurements of "b2" and "b3" and subsequently used to calculate the RE at 900 positions in nine clinically relevant beams. The extrapolated RE set was used to derive a simple linear correction function based on dose‐averaged LET (Ld) and verify the validity in all points of the comprehensive RE set. Results: The uncorrected film dose deviated up to 26% from the reference dose, whereas the corrected film dose agreed within 3% in all three beams in water ("b1", "b2" and "b3"). The LET dependence of the calibration function started to strongly increase around 5 keV/μm and flatten out around 30 keV/μm. All REs calculated from the proton fluence in the nine simulated beams could be approximated with a linear function of dose‐averaged LET (RE = 1.0258−0.0211 μm/keV Ld). However, no functional relationship of RE‐ and fluence‐averaged LET could be found encompassing all beam energies and modulations. Conclusions: The film quenching was found to be nonlinear as a function of proton LET as well as of the dose‐averaged LET. However, the linear relation of RE on dose‐averaged LET was a good approximation in all cases. In contrast to dose‐averaged LET, fluence‐averaged LET could not describe the RE when multiple beams were applied. [ABSTRACT FROM AUTHOR]

Gomŕ (2020 Phys. Med. Biol.) commented on our paper 'Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam photon and proton dosimetry' (Kuess et al 2017 Phys. Med. Biol. 62 9189–206) which describes a method to determine the response pattern of large-area ionization chambers using a collimated x-ray beam. Gomŕ performed a simple Monte Carlo simulation to investigate the energy transferred by secondary electrons within the detector, deducing that our conclusion, that the chamber has a non-uniform response, is not supported by our results. We appreciate the work performed by Gomŕ very much and believe that the transport of secondary electrons in the chamber is an important contribution to understand the non-uniformity response of large-area chambers in narrow beams. However, we disagree with the conclusions drawn by Gomŕ that the radial response is homogenous. His simulation actually demonstrates that the response is non-uniform in an x-ray beam. [ABSTRACT FROM AUTHOR]

Purpose: The feasibility of magnetic resonance image (MRI)‐based proton therapy is based, among several other factors, on the implementation of appropriate extensions on current dose calculation methods. This work aims to develop a pencil beam algorithm (PBA) for dose calculation of proton beams within magnetic field regions of up to 3 T. Methods: Monte Carlo (MC) simulations using the GATE 7.1/GEANT4.9.4p02 toolkit were performed to generate calibration and benchmarking data for the PBA. Dose distributions from proton beams in the clinical required energy range 60–250 MeV impinging on a 400 × 400 × 400 mm3 water phantom and transverse magnetic fields ranging from 0 to 3 T were considered. Energy depositions in homogeneous and heterogeneous phantoms filled with water, adipose, bone, and air were evaluated for proton energies of 80, 150, and 240 MeV, combining a trajectory calculation method and look‐up tables (LUT). A novel parametrization model, using independent tailed Gauss fitting functions, was employed to describe the nonsymmetric shape of lateral beam profiles. Integrated depth‐dose curves (IDD), lateral dose profiles, and two‐dimensional dose distributions calculated with the PBA were compared with results from MC simulations to assess the performance of the algorithm. A gamma index criterion of 2%/2 mm was used for analysis. Results: A close to perfect agreement was observed for PB‐based dose calculations in water in magnetic fields of 0.5, 1.5, and 3 T. IDD functions showed differences between the PBA and MC of less than 0.1% before the Bragg peak, and deviations of 2–8% in the distal energy falloff region. Gamma index pass rates higher than 99% and mean values lower than 0.1 were encountered for all analyzed configurations. For homogeneous phantoms, only the full bone configuration offered deviations in the Bragg peak position of up to 1.7% and overestimations of the lateral beam spot width for high‐energy protons and magnetic field intensities. An excellent agreement between PBA and MC dose calculation was also achieved using slab‐like and lateral heterogeneous phantoms, with gamma index passing rates above 98% and mean values between 0.1 and 0.2. As expected, agreement reduced for high‐energy protons and high‐intensity magnetic fields, although results remained good enough to be considered for future implementation in clinical practice. Conclusions: The proposed pencil beam algorithm for protons can accurately account for dose distortion effects induced by external magnetic fields. The application of an analytical model for dose estimation and corrections reduces the calculation times considerably, making the presented PBA a suitable candidate for integration in a treatment planning system. [ABSTRACT FROM AUTHOR]

Purpose To investigate and model effects of magnetic fields on proton and carbon ion beams for dose calculation. Methods In a first step, Monte Carlo simulations using Gate 7.1/Geant4.10.0.p03 were performed for proton and carbon ion beams in magnetic fields ranging from 0 to 3 T. Initial particle energies ranged from 60 to 250 MeV (protons) and 120 to 400 MeV/u (carbon ions), respectively. The resulting dose distributions were analyzed focusing on beam deflection, dose deformation, as well as the impact of material heterogeneities. In a second step, a numerical algorithm was developed to calculate the lateral beam position. Using the Runge-Kutta method, an iterative solution of the relativistic Lorentz equation, corrected for the changing particle energy during penetration, was performed. For comparison, a γ-index analysis was utilized, using a criteria of 2%/2 mm of the local maximum. Results A tilt in the dose distribution within the Bragg peak area was observed, leading to non-negligible dose distribution changes. The magnitude was found to depend on the magnetic field strength as well as on the initial beam energy. Comparison of the 3 T dose distribution with non-B field (nominal) dose distributions, resulted in a γ mean (mean value of the γ distribution) of 0.6, with 14.4% of the values above 1 and γ1% (1% of all points have an equal or higher γ value) of 1.8. The presented numerical algorithm calculated the lateral beam offset with maximum errors of less than 2% with calculation times of less than 5 μs. The impact of tissue interfaces on the proton dose distributions was found to be less than 2% for a dose voxel size of 1 × 1 × 1 mm3. Conclusion Non-negligible dose deformations at the Bragg peak area were identified for high initial energies and strong magnetic fields. A fast numerical algorithm based on the solution of the energy-corrected relativistic Lorentz equation was able to describe the beam path, taking into account the particle energy, magnetic field, and material. [ABSTRACT FROM AUTHOR]

Purpose: To develop a flexible pencil beam algorithm for helium ion beam therapy. Dose distributions were calculated using the newly developed pencil beam algorithm and validated using Monte Carlo (MC) methods. Methods: The algorithm was based on the established theory of fluence weighted elemental pencil beam (PB) kernels. Using a new real-time splitting approach, a minimization routine selects the optimal shape for each sub-beam. Dose depositions along the beam path were determined using a look-up table (LUT). Data for LUT generation were derived from MC simulations in water using GATE 6.1. For materials other than water, dose depositions were calculated by the algorithm using water-equivalent depth scaling. Lateral beam spreading caused by multiple scattering has been accounted for by implementing a non-local scattering formula developed by Gottschalk. A new nuclear correction was modelled using a Voigt function and implemented by a LUT approach. Validation simulations have been performed using a phantom filled with homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were incident perpendicular to the phantoms surface with initial particle energies ranging from 50 to 250 MeV/A with a total number of 107 ions per beam. For comparison a special evaluation software was developed calculating the gamma indices for dose distributions. Results: In homogeneous phantoms, maximum range deviations between PB and MC of less than 1.1% and differences in the width of the distal energy falloff of the Bragg-Peak from 80% to 20% of less than 0.1 mm were found. Heterogeneous phantoms using layered slabs satisfied a γ-index criterion of 2%/2mm of the local value except for some single voxels. For more complex phantoms using laterally arranged bone-air slabs, the γ-index criterion was exceeded in some areas giving a maximum γ-index of 1.75 and 4.9% of the voxels showed γ-index values larger than one. The calculation precision of the presented algorithm was considered to be sufficient for clinical practice. Although only data for helium beams was presented, the performance of the pencil beam algorithm for proton beams was comparable. Conclusions: The pencil beam algorithm developed for helium ions presents a suitable tool for dose calculations. Its calculation speed was evaluated to be similar to other published pencil beam algorithms. The flexible design allows easy customization of measured depth-dose distributions and use of varying beam profiles, thus making it a promising candidate for integration into future treatment planning systems. Current work in progress deals with RBE effects of helium ions to complete the model. [ABSTRACT FROM AUTHOR]

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Purpose: To investigate the possibility of detecting patient mispositioning in carbon-ion therapy with particle therapy positron emission tomography (PET) in an automated image registration based manner. Methods: Tumors in the head and neck (H&N), pelvic, lung, and brain region were investigated. Biologically optimized carbon ion treatment plans were created with TRiP98. From these treatment plans, the reference β+-activity distributions were calculated using a Monte Carlo simulation. Setup errors were simulated by shifting or rotating the computed tomography (CT). The expected β+ activity was calculated for each plan with shifts. Finally, the reference particle therapy PET images were compared to the 'shifted' β+-activity distribution simulations using the Pearson's correlation coefficient (PCC). To account for different PET monitoring options the inbeam PET was compared to three different inroom scenarios. Additionally, the dosimetric effects of the CT misalignments were investigated. Results: The automated PCC detection of patient mispositioning was possible in the investigated indications for cranio-caudal shifts of 4 mm and more, except for prostate tumors. In the rather homogeneous pelvic region, the generated β+-activity distribution of the reference and compared PET image were too much alike. Thus, setup errors in this region could not be detected. Regarding lung lesions the detection strongly depended on the exact tumor location: in the center of the lung tumor misalignments could be detected down to 2 mm shifts while resolving shifts of tumors close to the thoracic wall was more challenging. Rotational shifts in the H&N and lung region of +6° and more could be detected using inroom PET and partly using inbeam PET. Comparing inroom PET to inbeam PET no obvious trend was found. However, among the inroom scenarios a longer measurement time was found to be advantageous. Conclusions: This study scopes the use of various particle therapy PET verification techniques in four indications. The automated detection of patients' setup errors was investigated in a broad accumulation of data sets. The evaluation of introduced setup errors is performed automatically, which is of utmost importance to introduce highly required particle therapy monitoring devices into the clinical routine. [ABSTRACT FROM AUTHOR]

• 3D printed 2D/3D range modulators (2D/3DRM) offer advantages for light ion beam therapy, also in combination with pencil-beam scanning (PBS). • We designed 2DRMs with Monte Carlo simulations and validated them on a dosimetric as well as on a microdosimetric scale for both H and C12 beams. • The equivalence of using a single spot vs. a larger plan delivered via PBS with an appropriate 2DRM based on microdosimetric spectra is shown. Particle therapy using pencil beam scanning (PBS) faces large uncertain- ties related to ranges and target motion. One possibility to improve existing mitigation strategies is a 2D range modulator (2DRM). A 2DRM offers faster irradiation times by reducing the number of layers and spots needed to create a spread-out Bragg peak. We have investigated the impact of 2DRM on microdosimetric spectra measured in proton and carbon ion beams. Two 2DRMs were designed and 3D printed, one for. 124.7 MeV protons and one for 238.6 MeV/u carbon ions. Their dosimetric validation was performed using Roos and PinPoint ionization chamber and EBT3 films. Monte Carlo simulations were done using GATE. A silicon-based solid-state microdosimeter was used to collect pulse-height spectra along three depths for two irradiation modalities, PBS and a single central beam. For both particle types, the original pin design had to be optimized via GATE simulations. The difference between the R80 of the simulated and measured depth dose curve was 0. 1 mm. The microdosimetric spectra collected with the two irradiation modalities overlap well. Their mean lineal energy values differ over all positions by 5. 2 % for the proton 2DRM and 2. 1 % for the carbon ion 2DRM. Radiation quality in terms of lineal energy was independent of the irradiation method. This supports the current approach in reference dosimetry, where the residual range is chosen as a beam quality index to select stopping power ratios. [ABSTRACT FROM AUTHOR]

Background and purpose: In the next few years the number of facilities providing ion beam therapy with scanning beams will increase. An auditing process based on an end-to-end test (including CT imaging, planning and dose delivery) could help new ion therapy centres to validate their entire logistic chain of radiation delivery. An end-to-end procedure was designed and tested in both scanned proton and carbon ion beams, which may also serve as a dosimetric credentialing procedure for clinical trials in the future. The developed procedure is focused only on physical dose delivery and the validation of the biological dose is out of scope of the current work. Materials and methods: The audit procedure was based on a homogeneous phantom that mimics the dimension of a head (20×20×21cm3). The phantom can be loaded either with an ionisation chamber or 20 alanine dosimeters plus 2 radiochromic EBT films. Dose verification aimed at measuring a dose of 10Gy homogeneously delivered to a virtual-target volume of 8×8×12cm3. In order to interpret the readout of the irradiated alanine dosimeters additional Monte Carlo simulations were performed to calculate the energy dependent detector response of the particle fluence in the alanine detector. A pilot run was performed with protons and carbon ions at the Heidelberg Ion Therapy facility (HIT). Results: The mean difference of the absolute physical dose measured with the alanine dosimeters compared with the expected dose from the treatment planning system was −2.4±0.9% (1σ) for protons and −2.2±1.1% (1σ) for carbon ions. The measurements performed with the ionisation chamber indicate this slight underdosage with a dose difference of −1.7% for protons and −1.0% for carbon ions. The profiles measured by radiochromic films showed an acceptable homogeneity of about 3%. Conclusions: Alanine dosimeters are suitable detectors for dosimetry audits in ion beam therapy and the presented end-to-end test is feasible. If further studies show similar results, this dosimetric audit could be implemented as a credentialing procedure for clinical proton and carbon beam delivery. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of this study was to compare the dose calculation accuracy of advanced kernel-based methods and Monte Carlo algorithms in commercially available treatment planning systems. Materials and methods: Following dose calculation algorithms and treatment planning (TPS) systems were compared: the collapsed cone (CC) convolution algorithm available in Oncentra Masterplan, the XVMC Monte Carlo algorithm implemented in iPlan and Monaco, and the analytical anisotropic algorithm (AAA) implemented in Eclipse. Measurements were performed with a calibrated ionization chamber and radiochromic EBT type films in a homogenous polystyrene phantom and in heterogeneous lung phantoms. Single beam tests, conformal treatment plans and IMRT plans were validated. Dosimetric evaluations included absolute dose measurements, 1D γ-evaluation of depth–dose curves and profiles using 2mm and 2% dose difference criteria for single beam tests, and γ-evaluation of axial planes for composite treatment plans applying 3mm and 3% dose difference criteria. Results: Absolute dosimetry revealed no large differences between MC and advanced kernel dose calculations. 1D γ-evaluation showed significant discrepancies between depth–dose curves in different phantom geometries. For the CC algorithm γ mean values were 0.90±0.74 vs. 0.43±0.41 in heterogeneous vs. homogeneous conditions and for the AAA γ mean values were 1.13±0.91 vs. 0.41±0.28, respectively. In general, 1D γ results obtained with both MC TPS were similar in both phantoms and on average equal to 0.5 both for profiles and depth–dose curves. The results obtained with the CC algorithm in heterogeneous phantoms were slightly better in comparison to the AAA algorithm. The 2D γ-evaluation results of IMRT plans and four-field plans showed smaller mean γ-values for MC dose calculations compared to the advanced kernel algorithms (γ mean for four-field plan and IMRT obtained with Monaco MC were 0.28 and 0.5, respectively, vs. 0.40 and 0.54 for the AAA). Conclusion: All TPS investigated in this study demonstrated accurate dose calculation in homogenous and heterogeneous phantoms. Commercially available TPS with Monte Carlo option performed best in heterogeneous phantoms. However, the difference between the CC and the MC algorithms was found to be small. [Copyright &y& Elsevier]