Long-term stable optical cavity for special relativity tests in space: erratum.

We incorrectly cited a maximum acceleration sensitivity of the rigidly-mounted cavity of 2.5 × 10-10 1/(m s-2). The correct coupling factor is a factor of 100 smaller: 2.5 × 10-12 1/(m s-2).

Long-term stable optical cavity for special relativity tests in space.

BOOST (BOOst Symmetry Test) is a proposed space mission to search for Lorentz invariance violations and aims to improve the Kennedy-Thorndike parameter constraint by two orders of magnitude. The mission consists of comparing two optical frequency references of different nature, an optical cavity and a hyperfine transition in molecular iodine, in a low Earth orbit. Naturally, the stability of the frequency references at the orbit period of 5400 s (f=0.18 mHz) is essential for the mission success. Here we present our experimental efforts to achieve the required fractional frequency stability of 7.4×10-14 Hz -1/2 at 0.18 mHz (in units of the square root of the power spectral density), using a high-finesse optical cavity. We have demonstrated a frequency stability of (9±3)×10-14 Hz -1/2 at 0.18 mHz, which corresponds to an Allan deviation of 10-14 at 5400 s. A thorough noise source breakdown is presented, which allows us to identify the critical aspects to consider for a future space-qualified optical cavity for BOOST. The major noise contributor at sub-milli-Hertz frequency was related to intensity fluctuations, followed by thermal noise and beam pointing. Other noise sources had a negligible effect on the frequency stability, including temperature fluctuations, which were strongly attenuated by a five-layer thermal shield.

Comparing cone-beam CT intensity correction methods for dose recalculation in adaptive intensity-modulated photon and proton therapy for head and neck cancer.

BACKGROUND: Adaptive intensity-modulated photon and proton radiotherapy (IMRT and IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose calculation. We compared two approaches for dose recalculation on the basis of intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images. MATERIAL AND METHODS: For nine H&N tumor patients, virtual CTs (vCT) were generated by deformable image registration of the planning CT (pCT) to the CBCT. The second intensity correction approach used population-based lookup tables for scaling CBCT intensities to the pCT HU range (CBCTLUT). IMRT and IMPT plans were generated with a commercial treatment planning system. Dose recalculations on vCT and CBCTLUT were analyzed using a (3%, 3 mm) gamma-index analysis and comparison of normal tissue and tumor dose/volume parameters. A replanning CT (rpCT) acquired within three days of the CBCT served as reference. Single field uniform dose (SFUD) proton plans were created and recalculated on vCT and CBCTLUT for proton range comparison. RESULTS: Dose/volume parameters showed minor differences between rpCT, vCT and CBCTLUT in IMRT, but clinically relevant deviations between CBCTLUT and rpCT in the spinal cord for IMPT. Gamma-index pass-rates were found increased for vCT with respect to CBCTLUT in IMPT (by up to 21 percentage points) and IMRT (by up to 9 percentage points) for most cases. The SFUD-based proton range assessment showed improved agreement of vCT and rpCT, with 88-99% of the depth dose profiles in beam's eye view agreeing within 3 mm. For CBCTLUT, only 80-94% of the profiles fulfilled this criterion. CONCLUSION: vCT and CBCTLUT are suitable options for dose recalculation in adaptive IMRT. In the scope of IMPT, the vCT approach is preferable.

Investigation on the physical dose filtered by linear energy transfer for treatment plan evaluation in carbon ion therapy.

BACKGROUND: Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT. PURPOSE: Purpose of this study was to investigate on a novel dosimetric quantity, namely high-LET-dose ( D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ , the physical dose filtered based on an LET threshold) as a single parameter estimator to differentiate between carbon ion treatment plans (cTP) with a small and large tumor volume. METHODS: Ten cTPs with a planning target volume, PTV ≥ 500 cm 3 $\mathrm{PTV}\ge {500}\,{{\rm cm}^{3}}$ (large) and nine with a PTV < 500 cm 3 $\mathrm{PTV}<{500}\,{{\rm cm}^{3}}$ (small) were selected for this study. To find a reasonable LET threshold ( L thr $\textrm {L}_{\textrm {thr}}$ ) that results in a significant difference in terms of D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ , the voxel based normalized high-LET-dose ( D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) distribution in the clinical target volume (CTV) was studied on a subset (12 out of 19 cTPs) for 18 LET thresholds, using standard distribution descriptors (mean, variance and skewness). The classical dose volume histogram concept was used to evaluate the D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ distributions within the target of all 19 cTPs at the before determined L thr $\textrm {L}_{\textrm {thr}}$ . Statistical significance of the difference between the two groups in terms of mean D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ volume histogram parameters was evaluated by means of (two-sided) t-test or Mann-Whitney-U-test. In addition, the minimum target coverage at the above determined L thr $\textrm {L}_{\textrm {thr}}$ was compared and validated against three other thresholds to verify its potential in differentiation between small and large volume tumors. RESULTS: An L thr $\textrm {L}_{\textrm {thr}}$ of approximately 30 keV / µ m ${30}\,{\rm keV/}\umu {\rm m}$ was found to be a reasonable threshold to classify the two groups. At this threshold, the D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ were significantly larger ( p < 0.05 $p<0.05$ ) in small CTVs. For the small tumor group, the near-minimum and median D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ (and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) in the CTV were in average 9.3 ± 1.5 Gy $9.3\pm {1.5}\,{\rm Gy}$ (0.31 ± 0.08) and 13.6 ± 1.6 Gy $13.6\pm {1.6}\,{\rm Gy}$ (0.46 ± 0.06), respectively. For the large tumors, these parameters were 6.6 ± 0.2 Gy $6.6\pm {0.2}\,{\rm Gy}$ (0.20 ± 0.01) and 8.6 ± 0.4 Gy $8.6\pm {0.4}\,{\rm Gy}$ (0.28 ± 0.02). The difference between the two groups in terms of mean near-minimum and median D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ ( D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) was 2.7 Gy (11%) and 5.0 Gy (18%), respectively. CONCLUSIONS: The feasibility of high-LET-dose based evaluation was shown in this study where a lower D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ was found in cTPs with a large tumor size. Further investigation is needed to draw clinical conclusions. The proposed methodology in this work can be utilized for future high-LET-dose based studies.

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

BACKGROUND: Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd was reported. PURPOSE: The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). METHODS: Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than 250 cm 3 $250 \,{\rm cm}^{3}$ were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was D RBE , 50 % = 73.6 Gy $\textrm {D}_{\rm RBE, 50\%}=73.6 \,{\rm Gy}$ in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation 2023B. Three different Lmin values were investigated and specified for the seven boost fractions: L min = 60 keV / µ m $\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$ , L min = 80 keV / µ m $\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$ and L min = 100 keV / µ m $\textrm {L}_{\rm min}=100 \,{\rm keV}/{\umu }{\rm m}$ . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( ± 3.5 % $\pm 3.5\%$ range uncertainty and ± 3 mm $\pm 3 \,{\rm mm}$ setup uncertainty along the main three axes). RESULTS: The optimization method with L min = 60 keV / µ m $\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$ resulted in an optimal LETd distribution with an average increase of LET d , 98 % ${\rm {LET}}_{{\rm {d,}}98\%}$ (and LET d , 50 % ${\rm {LET}}_{{\rm {d,}}50\%}$ ) in the CTV-HD by 8.9 ± 1.5 keV / µ m $8.9\pm 1.5 \,{\rm keV}/{\umu }{\rm m}$ ( 27 % $27\%$ ) (and 6.9 ± 1.3 keV / µ m $6.9\pm 1.3 \,{\rm keV}/{\umu }{\rm m}$ ( 17 % $17\%$ )), without significant difference in the RBE-weighted dose. By allowing ± 5 % $\pm 5\%$ over- and under-dosage in the target, the LET d , 98 % ${\rm {LET}}_{{\rm {d,}}98\%}$ (and LET d , 50 % ${\rm {LET}}_{{\rm {d,}}50\%}$ ) can be increased by 11.3 ± 1.2 keV / µ m $11.3\pm 1.2 \,{\rm keV}/{\umu }{\rm m}$ ( 34 % $34\%$ ) (and 11.7 ± 3.4 keV / µ m $11.7\pm 3.4 \,{\rm keV}/{\umu }{\rm m}$ ( 29 % $29\%$ )), using the optimization parameters L min = 80 keV / µ m $\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$ . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to reference plans. CONCLUSIONS: Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects during treatment.

3D printed 2D range modulators preserve radiation quality on a microdosimetric scale in proton and carbon ion beams.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Small field proton irradiation for in vivo studies: Potential and limitations when adapting clinical infrastructure.

PURPOSE: To evaluate the dosimetric accuracy for small field proton irradiation relevant for pre-clinical in vivo studies using clinical infrastructure and technology. In this context additional beam collimation and range reduction was implemented. METHODS AND MATERIALS: The clinical proton beam line employing pencil beam scanning (PBS) was adapted for the irradiation of small fields at shallow depths. Cylindrical collimators with apertures of 15, 12, 7 and 5mm as well as two different range shifter types, placed at different distances relative to the target, were tested: a bolus range shifter (BRS) attached to the collimator and a clinical nozzle mounted range shifter (CRS) placed at a distance of 72cm from the collimator. The Monte Carlo (MC) based dose calculation engine implemented in the clinical treatment planning system (TPS) was commissioned for these two additional hardware components. The study was conducted with a phantom and cylindrical target sizes between 2 and 25mm in diameter following a dosimetric end-to-end test concept. RESULTS: The setup with the CRS provided a uniform dose distribution across the target. An agreement of better than5% between the planned dose and the measurements was obtained for a target with 3mm diameter (collimator 5mm). A 2mm difference between the collimator and the target diameter (target being 2 mm smaller than the collimator) sufficed to cover the whole target with the planned dose in the setup with CRS. Using the BRS setup (target 8mm, collimator 12mm) resulted in non-homogeneous dose distributions, with a dose discrepancy of up to 10% between the planned and measured doses. CONCLUSION: The clinical proton infrastructure with adequate beam line adaptations and a state-of-the-art TPS based on MC dose calculations enables small animal irradiations with a high dosimetric precision and accuracy for target sizes down to 3mm.

First microdosimetric measurements with a tissue-equivalent proportional counter at the MedAustron ion-beam therapy facility.

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.

Technical note: In silico benchmarking of the linear energy transfer-based functionalities for carbon ion beams in a commercial treatment planning system.

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/ µ $\umu$ m (3.5%) in the plateau and target and less than 2 keV/ µ $\umu$ m (8.3%) in the fragmentation tail. The maximum local differences were 4 and 6 keV/ µ $\umu$ m, 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.

Technical note: Experimental determination of the effective point of measurement of the PTW-31010 ionization chamber in proton and carbon ion beams.

PURPOSE: The accurate knowledge of the effective point of measurement (Peff ) is particularly important for measurements in proximity to high dose gradients such as in the distal fall-off of particle beams. For plane-parallel ionization chambers (ICs), Peff is well known and located at the center of the inner surface of the entrance window. For cylindrical ICs, Peff is shifted from the chamber's center toward the beam source. According to IAEA TRS-398, this shift can be calculated as 0.75·rcyl for light ions with rcyl being the radius of the cavity. For proton beams and in absence of a dose gradient, no shift is recommended. We have experimentally determined Peff for the 0.125 cc Semiflex IC in both proton and carbon ion beams. METHODS: The first method consisted of simultaneous irradiation of a plane-parallel IC and the Semiflex in a 4-cm wide spread-out Bragg peak. In the second method, a single-energy beam was used, and both ICs were positioned successively at the same measurement depths. For both approaches, the shift of the distal edge of the depth ionization distributions recorded by the two chambers at different reference points was used to calculate Peff of the Semiflex. Both methods were applied in carbon ion beams, and only the latter was applied in proton beams. RESULTS: Both methods yielded a similar Peff for carbon ions, 0.88·rcyl , and 0.84·rcyl , which results in a difference of only 0.1 mm. The difference to the recommended value of 0.75·rcyl is 0.4 and 0.3 mm, respectively, which is larger than the positioning uncertainty. In the proton beam, a Peff of 0.92·rcyl was obtained. CONCLUSIONS: The Peff for the 0.125 cc Semiflex IC is shifted further from the cavity center as recommended by IAEA TRS-398 for light ions, with the shift for proton beams being even larger than for carbon ion beams.

Accelerating and improving radiochromic film calibration by utilizing the dose ratio in photon and proton beams.

PURPOSE: Radiochromic films are versatile 2D dosimeters with high-resolution and near tissue equivalence. To assure high precision and accuracy, a time-consuming calibration process is required. To improve the time efficiency, a novel calibration method utilizing the ratio of the same dose profile measured at different monitor units (MUs) is introduced and tested in a proton and photon beam. METHODS: The calibration procedure employs the dose ratio of film measurements of the same relative profile for different absolute dose values. Hence, the ratio of the dose is constant at any point of the profile, but the ratio of the net optical densities is not constant. The key idea of the method is to optimize the calibration function until the ratio of the calculated doses is constant. The proposed method was tested in the dose range between 0.25-12 and 1-6 Gy in a proton and photon beam, respectively. A radial symmetric profile and a rectangular profile were created, both having a central plateau region of about 3 cm diameter and a dose falloff of about 1.5 cm at larger distances. The dose falloff region was used as input for the optimization method and the central plateau region served as dose reference points. Only the plateau region of the highest dose entered the optimization as an additional objective. The measured data were randomly split into differently sized training and test sets. The optimization was repeated 1000 times with random start value initialization using the same start values for the standard and the gradient method. Finally, a proton plan with four dose levels was created, which were separated spatially, to test the possibility of a full calibration within a single measurement. RESULTS: Parameter estimation was possible with as low as one dose ratio used for optimization in both the photon and the proton case, yet exhibiting a high sensitivity on the dose level. The root mean squared deviation (RMSD) of the dose was less than 1% when the dose ratio was in the order of 20, whereas the median RMSD of all optimizations was 1.7%. Using four dose levels for optimization resulted in a median RMSD of 1% when randomly selecting the dose levels. Having at least one dose ratio of about 20 included in the optimization considerably improved the RMSD of the calibration function. Using six or eight dose levels reduced the sensitivity on the dose level selection and the median RMSD was 0.8%. A full calibration was possible in a single measurement having four dose levels in one plan but spatially separated. CONCLUSIONS: The number of measurements required to obtain an EBT3 film calibration function could be reduced using the proposed dose ratio method while maintaining the same accuracy as with the standard method.

Technical note: Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy.

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.

The practical radius of a pencil beam in proton therapy.

The central Gaussian shaped high dose region of a pencil beam (PB) in light ion beam therapy (LIBT) is enveloped by a low dose region causing non-negligible field size effects and impairs the dose calculation accuracy considerably if the low dose envelope is not well modeled. The purpose of this study was to calculate the practical radius, Rc, at which a PB does not influence a field more than a certain accuracy level. Lateral dose profiles of proton beams in water were simulated using GATE/Geant4. Those lateral dose profiles were integrated numerically and used to calculate field size factors (FSFs). The Rc was then determined such, that the lateral dose at radii exceeding Rc can be neglected without compromising the FSF of a 20cm×20cm field more than a desired accuracy level c. The practical radius Rc yielding c=0.5% was compared to the frequently applied concept of full width at a ratio x of the maximum (FWxM). The sensitivity to variations of the beam width was tested by increasing the initial beam width σC of the clinical beam model by 0.5 and 1mm, respectively. Neglecting the dose at radii exceeding Rc resulted in the desired FSF accuracy, whereas using the FW0.01%M cut resulted in varying accuracy. In order to yield a constant FSF accuracy, the ratio x in FWxM ranged from 0.003% to 0.065% of the maximum. In contrast to Rc, FWxM was sensitive to variations of the initial beam width. The maximum Rc over all depths was less than 7cm for the low(62.4MeV) and medium(148.2MeV) proton energy beam, which suggests that a plane parallel ionization chamber exceeding that radius is sufficient to acquire laterally integrated depth dose distributions for those energies. However, this holds not true for the highest energy (252.7MeV) or when including a range shifter (RaShi). The values of Rc are specific to our beam line configuration as the maximum Rc was depending on both, the scattering material in the Nozzle as well as the distance of the air-gap between Nozzle and phantom.

Computer-assisted beam modeling for particle therapy.

PURPOSE: To develop a computer-driven and thus less user-dependent method, allowing for a simple and straightforward generation of a Monte Carlo (MC) beam model of a scanned proton and carbon ion beam delivery system. METHODS: In a first step, experimental measurements were performed for proton and carbon ion energies in the available energy ranges. Data included depth dose profiles measured in water and spot sizes in air at various isocenter distances. Using an automated regularization-based optimization process (AUTO-BEAM), GATE/Geant4 beam models of the respective beam lines were generated. These were obtained sequentially by using least square weighting functions with and without regularization, to iteratively tune the beam parameters energy, energy spread, beam sigma, divergence, and emittance until a user-defined agreement was reached. Based on the parameter tuning for a set of energies, a beam model was semi-automatically generated. The resulting beam models were validated for all centers comparing to independent measurements of laterally integrated depth dose curves and spot sizes in air. For one representative center, three-dimensional dose cubes were measured and compared to simulations. The method was applied on one research as well as four different clinical beam lines for proton and carbon ions of three different particle therapy centers using synchrotron or cyclotron accelerator systems: (a) MedAustron ion therapy center, (b) University Proton Therapy Dresden, and (c) Center Antoine Lacassagne Nice. RESULTS: Particle beam ranges in the MC beam models agreed on average within 0.2 mm compared to measurements for all energies and beam lines. Spot sizes in air (full-width at half maximum) at all positions differed by less than 0.4% from the measurements. Dose calculation with the beam model for the clinical beam line at MedAustron agreed better than 1.7% in absolute dose for a representative clinical case treated with protons. For protons, beam model generation, including geometry creation, data conversion, and validation, was possible within three working days. The number of iterations required for the optimization process to converge, was found to be similar for all beam line geometries and particle types. CONCLUSION: The presented method was demonstrated to work independently of the beam optics behavior of the different beam lines, particle types, and geometries. Furthermore, it is suitable for non-expert users and requires only limited user interaction. Beam model validation for different beam lines based on different beam delivery systems, showed good agreement.

Implementation of a dose calculation algorithm based on Monte Carlo simulations for treatment planning towards MRI guided ion beam therapy.

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 (D2%, D50%, D90%, V95% and V105%) 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.

Dose- rather than fluence-averaged LET should be used as a single-parameter descriptor of proton beam quality for radiochromic film dosimetry.

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 " b 1 ") 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 " b 1 ", which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration " b 2 " and " b 3 ," 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 " b 1 ." This method was then validated on the measurements of " b 2 " and " b 3 " 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 ( L d ) 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 (" b 1 ", " b 2 " and " b 3 "). 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 L d ). 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.

Benchmarking a GATE/Geant4 Monte Carlo model for proton beams in magnetic fields.

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.

A GATE/Geant4 beam model for the MedAustron non-isocentric proton treatment plans quality assurance.

PURPOSE: To present a reference Monte Carlo (MC) beam model developed in GATE/Geant4 for the MedAustron fixed beam line. The proposed model includes an absolute dose calibration in Dose-Area-Product (DAP) and it has been validated within clinical tolerances for non-isocentric treatments as routinely performed at MedAustron. MATERIAL AND METHODS: The proton beam model was parametrized at the nozzle entrance considering optic and energy properties of the pencil beam. The calibration in terms of absorbed dose to water was performed exploiting the relationship between number of particles and DAP by mean of a recent formalism. Typical longitudinal dose distribution parameters (range, distal penumbra and modulation) and transverse dose distribution parameters (spot sizes, field sizes and lateral penumbra) were evaluated. The model was validated in water, considering regular-shaped dose distribution as well as clinical plans delivered in non-isocentric conditions. RESULTS: Simulated parameters agree with measurements within the clinical requirements at different air gaps. The agreement of distal and longitudinal dose distribution parameters is mostly better than 1 mm. The dose difference in reference conditions and for 3D dose delivery in water is within 0.5% and 1.2%, respectively. Clinical plans were reproduced within 3%. CONCLUSION: A full nozzle beam model for active scanning proton pencil beam is described using GATE/Geant4. Absolute dose calibration based on DAP formalism was implemented. The beam model is fully validated in water over a wide range of clinical scenarios and will be inserted as a reference tool for research and for independent dose calculation in the clinical routine.

Evaluation of GATE-RTion (GATE/Geant4) Monte Carlo simulation settings for proton pencil beam scanning quality assurance.

PURPOSE: Geant4 is a multi-purpose Monte Carlo simulation tool for modeling particle transport in matter. It provides a wide range of settings, which the user may optimize for their specific application. This study investigates GATE/Geant4 parameter settings for proton pencil beam scanning therapy. METHODS: GATE8.1/Geant4.10.3.p03 (matching the versions used in GATE-RTion1.0) simulations were performed with a set of prebuilt Geant4 physics lists (QGSP_BIC, QGSP_BIC_EMY, QGSP_BIC_EMZ, QGSP_BIC_HP_EMZ), using 0.1mm-10mm as production cuts on secondary particles (electrons, photons, positrons) and varying the maximum step size of protons (0.1mm, 1mm, none). The results of the simulations were compared to measurement data taken during clinical patient specific quality assurance at The Christie NHS Foundation Trust pencil beam scanning proton therapy facility. Additionally, the influence of simulation settings was quantified in a realistic patient anatomy based on computer tomography (CT) scans. RESULTS: When comparing the different physics lists, only the results (ranges in water) obtained with QGSP_BIC (G4EMStandardPhysics_Option0) depend on the maximum step size. There is clinically negligible difference in the target region when using High Precision neutron models (HP) for dose calculations. The EMZ electromagnetic constructor provides a closer agreement (within 0.35 mm) to measured beam sizes in air, but yields up to 20% longer execution times compared to the EMY electromagnetic constructor (maximum beam size difference 0.79 mm). The impact of this on patient-specific quality assurance simulations is clinically negligible, with a 97% average 2%/2 mm gamma pass rate for both physics lists. However, when considering the CT-based patient model, dose deviations up to 2.4% are observed. Production cuts do not substantially influence dosimetric results in solid water, but lead to dose differences of up to 4.1% in the patient CT. Small (compared to voxel size) production cuts increase execution times by factors of 5 (solid water) and 2 (patient CT). CONCLUSIONS: Taking both efficiency and dose accuracy into account and considering voxel sizes with 2 mm linear size, the authors recommend the following Geant4 settings to simulate patient specific quality assurance measurements: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (in the phantom and range-shifter) and 10 mm (world); best agreement to measurement data was found for QGSP_BIC_EMZ reference physics list at the cost of 20% increased execution times compared to QGSP_BIC_EMY. For simulations considering the patient CT model, the following settings are recommended: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (phantom/range-shifter) and 10 mm (world) if the goal is to achieve sufficient dosimetric accuracy to ensure that a plan is clinically safe; or 0.1 mm (phantom/range-shifter) and 1 mm (world) if higher dosimetric accuracy is needed (increasing execution times by a factor of 2); most accurate results expected for QGSP_BIC_EMZ reference physics list, at the cost of 10-20% increased execution times compared to QGSP_BIC_EMY.

Evaluation of electromagnetic and nuclear scattering models in GATE/Geant4 for proton therapy.

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.