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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.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.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.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.

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 (IC), 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 towards 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. This article is protected by copyright. All rights reserved.

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.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.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.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.

PURPOSE This work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS. METHODS All treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24-pinpoint ionization chamber array (T31015, PTW, Germany). Tissue-like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm3 was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated. RESULTS Inside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone-lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes. CONCLUSION The pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk.

Purpose This paper presents the implementation and comparison of two independent methods of beam monitor calibration in terms of number of particles for scanned proton and carbon ion beams. Methods In the first method, called the single-layer method, dose-area-product to water ( D A P w ) is derived from the absorbed dose to water determined using a Roos-type plane-parallel ionization chamber in single-energy scanned beams. This is considered the reference method for the beam monitor calibration in the clinically relevant proton and carbon energy ranges. In the second method, called the single-spot method, DAP w of a single central spot is determined using a Bragg-peak (BP) type large-area plane-parallel ionization chamber. Emphasis is given to the detailed characterization of the ionization chambers used for the beam monitor calibration. For both methods a detailed uncertainty budget on the DAP w determination is provided as well as on the derivation of the number of particles. Results Both calibration methods agreed on average within 1.1% for protons and within 2.6% for carbon ions. The uncertainty on DAP w using single-layer beams is 2.1% for protons and 3.1% for carbon ions with major contributions from the available values of kQ and the average spot spacing in both lateral directions. The uncertainty using the single-spot method is 2.2% for protons and 3.2% for carbon ions with major contributions from the available values of kQ and the non-uniformity of the BP chamber response, which can lead to a correction of up-to 3.2%. For the number of particles, an additional dominant uncertainty component for the mean stopping power per incident proton (or the CEMA) needs to be added. Conclusion The agreement between both methods enhances confidence in the beam monitor calibration and the estimated uncertainty. The single-layer method can be used as a reference and the single-spot method is an alternative that, when more accumulated knowledge and data on the method becomes available, can be used as a redundant dose monitor calibration method. This work, together with the overview of information from the literature provided here, is a first step towards comprehensive information on the single-spot method.

Purpose To investigate the response of detectors for proton dosimetry in the presence of magnetic fields. Material and methods Four ionization chambers (ICs), two thimble-type and two plane-parallel-type, and a diamond detector were investigated. All detectors were irradiated with homogeneous single-energy-layer fields, using 252.7 MeV proton beams. A Farmer IC was additionally irradiated in the same geometrical configuration, but with a lower nominal energy of 97.4 MeV. The beams were subjected to magnetic field strengths of 0, 0.25, 0.5, 0.75, and 1 T produced by a research dipole magnet placed at the room's isocenter. Detectors were positioned at 2 cm water equivalent depth, with their stem perpendicular to both the magnetic field lines and the proton beam's central axis, in the direction of the Lorentz force. Normality and two sample statistical Student's t tests were performed to assess the influence of the magnetic field on the detectors' responses. Results For all detectors, a small but significant magnetic field-dependent change of their response was found. Observed differences compared to the no magnetic field case ranged from +0.5% to -0.7%. The magnetic field dependence was found to be nonlinear and highest between 0.25 and 0.5 T for 252.7 MeV proton beams. A different variation of the Farmer chamber response with magnetic field strength was observed for irradiations using lower energy (97.4 MeV) protons. The largest magnetic field effects were observed for plane-parallel ionization chambers. Conclusion Small magnetic field-dependent changes in the detector response were identified, which should be corrected for dosimetric applications.

Purpose This paper presents a novel method for the calculation of three-dimensional (3D) Bragg-Gray water-to-detector stopping power ratio (sw,det ) distributions for proton and carbon ion beams. Methods Contrary to previously published fluence-based calculations of the stopping power ratio, the sw,det calculation method used in this work is based on the specific way GATE/Geant4 scores the energy deposition. It only requires the use of the so-called DoseActor, as available in GATE, for the calculation of the sw,det at any point of a 3D dose distribution. The simulations are performed using GATE-RTion v1.0, a dedicated GATE release that was validated for the clinical use in light ion beam therapy. Results The Bragg-Gray water-to-air stopping power ratio (sw,air ) was calculated for monoenergetic proton and carbon ion beams with the default stopping power data in GATE-RTion v1.0 and the new ICRU90 recommendation. The sw,air differences between the use of the default and the ICRU90 configuration were 0.6% and 5.4% at the physical range (R80 - 80% dose level in the distal dose fall-off) for a 70 MeV proton beam and a 120 MeV/u carbon ion beam, respectively. For protons, the sw,det results for lithium fluoride, silicon, gadolinium oxysulfide, and the active layer material of EBT2 (radiochromic film) were compared with the literature and a reasonable agreement was found. For a real patient treatment plan, the 3D distributions of sw,det in proton beams were calculated. Conclusions Our method was validated by comparison with available literature data. Its equivalence with Bragg-Gray cavity theory was demonstrated mathematically. The capability of GATE-RTion v1.0 for the sw,det calculation at any point of a 3D dose distribution for simple and complex proton and carbon ion plans was presented.

Purpose: The local depth dose gradient and the displacement correction factor for Farmer-type ionization chambers are quantified for reference dosimetry at shallow depth in single-layer scanned proton fields. Method: Integrated radial profiles as a function of depth (IRPDs) measured at three proton therapy centers were smoothed by polynomial fits. The local relative depth dose gradient at measurement depths from 1 to 5 cm were derived from the derivatives of those fits. To calculate displacement correction factors, the best estimate of the effective point of measurement was derived from reviewing experimental and theoretical determinations reported in the literature. Displacement correction factors for the use of Farmer-type ionization chambers with their reference point (at the center of the cavity volume) positioned at the measurement depth were derived as a ratio of IRPD values at the measurement depth and at the effective point of measurement. Results: Depth dose gradients are as low as 0.1–0.4% per mm at measurement depths from 1 to 5 cm in the highest clinical proton energies (with residual ranges higher than 15 cm) and increase to 1% per mm at a residual range of 4 cm and become larger than 3% per mm for residual ranges lower than 2 cm. The literature review shows that the effective point of measurement of Farmer-type ionization chambers is, similarly as for carbon ion beams, located 0.75 times the cavity radius closer to the beam origin as the center of the cavity. If a maximum displacement correction of 2% is deemed acceptable to be included in calculated beam quality correction factors, Farmer-type ICs can be used at measurements depths from 1 to 5 cm for which the residual range is 4 cm or larger. If one wants to use the same beam quality correction factors as applicable to the conventional measurement point for scattered beams, located at the center of the SOBP, the relative standard uncertainty on the assumption that the displacement correction factor is unity can be kept below 0.5% for measurement depths of at least 2 cm and for residual ranges of 15 cm or higher. Conclusion: The literature review confirmed that for proton beams the effective point of measurement of Farmer-type ionization chambers is located 0.75 times the cavity radius closer to the beam origin as the center of the cavity. Based on the findings in this work, three options can be recommended for reference dosimetry of scanned proton beams using Farmer-type ionization chambers: (a) positioning the effective point of measurement at the measurement depth, (b) positioning the reference point at the measurement depth and applying a displacement correction factor, and (c) positioning the reference point at the measurement depth without applying a displacement correction factor. Based on limiting the acceptable uncertainty on the gradient correction factor to 0.5% and the maximum deviation of the displacement perturbation correction factor from unity to 2%, the first two options can be allowed for residual ranges of at least 4 cm while the third option only for residual ranges of at least 15 cm.

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 “ (Formula presented.) ”) 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 “ (Formula presented.) ”, which contributed either 50% of the initial particle fluence or 50% of the dose in the SOBP, referred to as configuration “ (Formula presented.) ” and “ (Formula presented.), ” 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 “ (Formula presented.).” This method was then validated on the measurements of “ (Formula presented.) ” and “ (Formula presented.) ” 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 ((Formula presented.)) 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 (“ (Formula presented.) ”, “ (Formula presented.) ” and “ (Formula presented.) ”). 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 (Formula presented.)). 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.

PURPOSE To present an analytical formalism for the in depth assessment of uncertainties of field output factors in small fields related to detector positioning based on dose profile measurements. Additionally, a procedure for the propagation of these uncertainties was developed. METHODS Based on the assumption that one dimensional and two dimensional second-order polynomial functions can be fitted to dose profiles of small photon beams, equations for the calculation of the expectation value, the variance, and the standard deviation were developed. The following fitting procedures of the dose profiles were considered: A one-dimensional case (1D), a quasi two-dimensional case (2Dq) based on independently measured line profiles and a full 2D case (2Df) which also considers cross-correlations in a two-dimensional dose distribution. A rectangular and a Gaussian probability density function (PDF) characterizing the probability of possible positions of the detector relative to the maximum dose were used. Uncertainty components such as the finite resolution of the scanning water phantom, the reproducibility of the determination of the position of the maximum dose, and the reproducibility of the collimator system were investigated. This formalism was tested in a 0.5 x 0.5 cm2 photon field where dose profiles were measured using a radiochromic film, a synthetic diamond detector, and an unshielded diode detector. Additionally, the dose distribution measured with the radiochromic film was convoluted with a convolution kernel mimicking the active volume of the unshielded diode. RESULTS Analytic expressions for the calculation of uncertainties on field output factors were found for the 1D, the 2Dq, and the 2Df case. The uncertainty of the field output factor related to the relative position of the detector to the maximum dose increased quadratically with increasing limits of possible detector positions. Analysis of the radiochromic film showed that the 2Dq case gave a more conservative assessment of the uncertainty compared to the 2Df case with a difference of

The purpose of this paper is to compare the response of two different types of solid-state microdosimeters, that is, silicon and diamond, and their uncertainties. A study of the conversion of silicon microdosimetric spectra to the diamond equivalent for microdosimeters with different geometry of the sensitive volumes is performed, including the use of different stopping power databases.Diamond and silicon microdosimeters were irradiated under the same conditions, aligned at the same depth in a carbon-ion beam at the MedAustron ion therapy center. In order to estimate the microdosimetric quantities, the readout electronic linearity was investigated with three different methods, that is, the first being a single linear regression, the second consisting of a double linear regression with a channel transition and last a multiple linear regression by splitting the data into odd and even groups. The uncertainty related to each of these methods was estimated as well. The edge calibration was performed using the intercept with the horizontal axis of the tangent through the inflection point of the Fermi function approximation multi-channel analyzer spectrum. It was assumed that this point corresponds to the maximum energy difference of particle traversing the sensitive volume (SV) for which the residual range difference in the continuous slowing down approximation is equal to the thickness of the SV of the microdosimeter. Four material conversion methods were explored, the edge method, the density method, the maximum-deposition energy method and the bin-by-bin transformation method. The uncertainties of the microdosimetric quantities resulting from the linearization, the edge calibration and the detectors thickness were also estimated.It was found that the double linear regression had the lowest uncertainty for both microdosimeters. The propagated standard (k = 1) uncertainties on the frequency-mean lineal energyThis article demonstrate that the linearity of the readout electronics affects the microdosimetric spectra with a difference in

Purpose This paper describes the clinical implementation and medical commissioning of the MedAustron Particle Therapy Accelerator (MAPTA) for non-isocentric scanned proton beam treatments. Methods Medical physics involvement during technical commissioning work is presented. Acceptance testing procedures, including advanced measurement methods of intra-spill beam variations, are defined. Beam monitor calibration using two independent methods based on a dose-area product formalism is described. Emphasis is given to the medical commissioning work and the specificities related to non-isocentric irradiation, since a key feature of MedAustron is the routine delivery of non-isocentric scanned proton beam treatments. Results Key commissioning results and beam stability trend lines for more than 2 yr of clinical operation have been provided. Intra-spill beam range, size, and position variations were within specifications of 0.3 mm, 15%, and 0.5 mm, respectively. The agreement between two independent beam monitor calibration methods was better than 1.0%. Non-isocentric treatment delivery allowed lateral penumbra reduction of up to about 30%. Daily QA measurements of the beam range, size, position, and dose were always within 1 mm, 10%, 1 mm, and 2% from the baseline data, respectively. Conclusions Non-isocentric treatments have been successfully implemented at MedAustron for routine scanned proton beam therapy using horizontal and vertical fixed beamlines. Up to now every patient was treated in non-isocentric conditions. The presented methodology to implement a new Scanned Ion Beam Delivery (SIBD) system into clinical routine for proton therapy may serve as a guidance for other centers.

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

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.

Objective. To review the currently available data on beam quality correction factors, k Q , for ionization chambers in clinical proton beams and derive their current best estimates for the updated recommendations of the IAEA TRS-398 Code of Practice. Approach. The reviewed data come from 20 publications from which k Q values can be derived either directly from calorimeter measurements, indirectly from comparison with other chambers or from Monte Carlo calculated overall chamber factors, f Q . For cylindrical ionization chambers, a distinction is made between data obtained in the centre of a spread-out Bragg peak and those obtained in the plateau region of single-energy fields. For the latter, the effect of depth dose gradients has to be considered. To this end an empirical model for previously published displacement correction factors for single-layer scanned beams was established, while for unmodulated scattered beams experimental data were used. From all the data, chamber factors, f Q , and chamber perturbation correction factors, p Q , were then derived and analysed. Main results. The analysis showed that except for the beam quality dependence of the water-to-air mass stopping power ratio and, for cylindrical ionization chambers in unmodulated beams, of the displacement correction factor, there is no remaining beam quality dependence of the chamber perturbation correction factors p Q . Based on this approach, average values of the beam quality independent part of the perturbation factors were derived to calculate k Q values consistent with the data in the literature. Significance. The resulting data from this analysis are current best estimates of k Q values for modulated scattered beams and single-layer scanned beams used in proton therapy. Based on this, a single set of harmonized values is derived to be recommended in the update of IAEA TRS-398.

Recent results from pre-clinical studies investigating the so-called FLASH effect suggest that the ultrahigh pulse dose rates (UHPDR) of this modality reduces normal tissue damage whilst preserving tumour response, when compared with conventional radiotherapy (RT). FLASH-RT is characterized by average dose rates of dozens of Gy/s instead of only a few Gy/min. For some studies, dose rates exceeding hundreds of Gy/s have been used for investigating the tissue response. Moreover, depending on the source of radiation, pulsed beams can be used with low repetition rate and large doses per pulse. Accurate dosimetry of high dose-rate particle beams is challenging and requires the development of novel dosimetric approaches, complementary to the ones used for conventional radiotherapy. The European Joint Research Project “UHDpulse” will develop a measurement framework, encompassing reference standards traceable to SI units and validated reference methods for dose measurements with UHPDR beams. In this paper, the UHDpulse project will be presented, discussing the dosimetric challenges and showing some first results obtained in experimental campaigns with pulsed electron beams and laser-driven proton beams.

Purpose An independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe. Methods The audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10 Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom. Results For all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was −0.1 ± 1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of −0.5 ± 0.6%. Conclusion The developed dosimetry audit method was successfully applied at five proton centers including various “turn-key” Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.

Purpose The aims of this work are to study the response of a small-gap plane-parallel ionization chamber in the presence of charge multiplication and suggest an experimental method to determine the product of the recombination correction factor (ks) and the charge multiplication correction factor (kCM) in order to investigate the latter. Methods Experimental data were acquired in scanned proton beams and in a Cobalt-60 beam. Measurements were carried out using an IBA PPC05 chambers of which the electrode gap is 0.6 mm. The study is based on the determination of Jaffe plots by operating the chambers at different voltages. Experimental results are compared to theoretical equations describing initial and volume recombination as well as charge multiplication for continuous and pulsed beams. Results Results obtained in protons and Cobalt-60 with the same PPC05 chamber indicate that the charge multiplication effect is independent of the beam quality, while results obtained in different proton beams with two different PPC05 chambers show that the charge multiplication effect is chamber dependent. Conclusions The approach to be taken when using a small-gap plane-parallel ionization chamber with a high voltage (e.g. 300 V or 500 V) for reference dosimetry in scanned proton beams depends on which correction factors were applied to the chamber response during its calibration in terms of absorbed dose to water: - if ks and kCM are applied during the calibration, the user can use a linear extrapolation method (e.g. two-voltage method or 3VL-method) to determine the product of ks and kCM in the user beam. - if ks and kCM are not applied during the calibration: the user can neglect kCM and determine ks in the user beams using a linear interpolation of the chamber response. In both cases, it is recommended to use the ionization chamber at the same operating voltage used during its ND,w-calibration. Another solution consists of operating the PPC05 chamber at a lower voltage (e.g. 50 V) with larger ks and smaller kCM and determining the product of both factors with higher accuracy using a linear extrapolation method.

High dose-rate radiotherapy, known as FLASH, has been shown to increase the differential response between healthy and tumour tissue. Moreover, Very High Energy Electrons (VHEEs) provide more favourable dose distributions than conventional radiotherapy electron and photon beams. Plane-parallel ionisation chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons, therefore chamber response to these high energy and high dose-per-pulse beams must be well understood. Graphite calorimetry, the UK primary standard, has been employed to measure the dose delivered from a 200 MeV pulsed electron beam. This was compared to the charge measurements of a plane-parallel ionisation chamber to determine the absolute collection efficiency and infer the ion recombination factor. The dose-per-pulse measured by the calorimeter ranged between 0.03 Gy/pulse and 5.26 Gy/pulse, corresponding to collection efficiencies between 97% and 4%, respectively. Multiple recombination models currently available have been compared with experimental results. This work is directly applicable to the development of standard dosimetry protocols for VHEE radiotherapy, FLASH radiotherapy and other high dose-rate modalities. However, the use of secondary standard ionisation chambers for the dosimetry of high dose-per-pulse VHEEs has been shown to require large corrections for charge collection inefficiency.

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.

Four-dimensional dose calculation (4D-DC) is crucial for predicting the dosimetric outcome in the presence of intra-fractional organ motion. Time-resolved dosimetry can provide significant insights into 4D pencil beam scanning dose accumulation and is therefore irreplaceable for benchmarking 4D-DC. In this study a novel approach of time-resolved dosimetry using five PinPoint ionization chambers (ICs) embedded in an anthropomorphic dynamic phantom was employed and validated against beam delivery details. Beam intensity variations as well as the beam delivery time structure were well reflected with an accuracy comparable to the temporal resolution of the IC measurements. The 4D dosimetry approach was further applied for benchmarking the 4D-DC implemented in the RayStation 6.99 treatment planning system. Agreement between computed values and measurements was investigated for (i) partial doses based on individual breathing phases, and (ii) temporally distributed cumulative doses. For varied beam delivery and patient-related parameters the average unsigned dose difference for (i) was 0.04 +/- 0.03 Gy over all considered IC measurement values, while the prescribed physical dose was 2 Gy. By implementing (ii), a strong effect of the dose gradient on measurement accuracy was observed. The gradient originated from scanned beam energy modulation and target motion transversal to the beam. Excluding measurements in the high gradient the relative dose difference between measurements and 4D-DCs for a given treatment plan at the end of delivery was 3.5% on average and 6.6% at maximum over measurement points inside the target. Overall, the agreement between 4D dose measurements in the moving phantom and retrospective 4D-DC was found to be comparable to the static dose differences for all delivery scenarios. The presented 4D-DC has been proven to be suitable for simulating treatment deliveries with various beam- as well as patient-specific parameters and can therefore be employed for dosimetric validation of different motion mitigation techniques.

This article reviews the development and summarizes the state-of-the-art in absorbed dose calorimetry for all the common clinical beam modalities covered in reference dosimetry codes of practice, as well as for small and nonstandard fields, and brachytherapy. It focuses primarily on work performed in the last ten years by national laboratories and research institutions and is not restricted to primary standard instruments. The most recent absorbed dose calorimetry review article was published over twenty years ago by Ross and Klassen (1996 Phys. Med. Biol. 41 1-29), and even then, its scope was limited to water calorimeters. Since the application of calorimetry to the measurement of radiation has a long and often overlooked history, a brief introduction into its origins is provided, along with a summary of some of the landmark research that have shaped the current landscape of absorbed dose calorimeters. Technical descriptions of water and graphite calorimetry are kept general, as these have been detailed extensively in relatively recent review articles (e.g. McEwen and DuSautoy (2009 Metrologia 46 S59-79) and Seuntjens and Duane (2009 Metrologia 46 S39-58). The review categorizes calorimeters by the radiation type for which they are applied; from the widely established standards for Co-60 and high-energy x-rays, to the prototype calorimeters used in high-energy electrons and hadron therapy. In each case, focus is placed on the issues and constraints affecting dose measurement in that beam type, and the innovations developed to meet these requirements. For photons, electrons, proton and carbon ion beams, a summary of the ionization chamber beam quality conversion factors (k Q ) determined using said calorimeters is also provided. The article closes with a look forward to some of the most promising new techniques and areas of research and speculates about the future clinical role of absorbed dose calorimetry.

Despite well-established dosimetry in clinical radiotherapy, dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of published findings. The lack of suitable dosimetry protocols, coupled with the increasing complexity of pre-clinical irradiation platforms, undermines confidence in preclinical studies and represents a serious obstacle in the translation to clinical practice. To accurately measure output of a pre-clinical radiotherapy unit, appropriate Codes of Practice (CoP) for medium energy x-rays needs to be employed. However, determination of absorbed dose to water (Dw) relies on application of backscatter factor (Bw) employing in-air method or carrying out in-phantom measurement at the reference depth of 2 cm in a full backscatter (i.e. 30 × 30 × 30 cm3) condition. Both of these methods require thickness of at least 30 cm of underlying material, which are never fulfilled in typical pre-clinical irradiations. This work is focused on evaluation the effects of the lack of recommended reference conditions in dosimetry measurements for pre-clinical settings and is aimed at extending the recommendations of the current CoP to practical experimental conditions and highlighting the potential impact of the lack of correct backscatter considerations on radiobiological studies. ispartof: PHYSICS IN MEDICINE AND BIOLOGY vol:65 issue:8 ispartof: location:England status: published

The monolithic silicon telescope technology allows to produce solid state microdosimeters. A detector constituted by a matrix of pixels (2 μm in thickness) coupled with a deeper stage (about 500 μm in thickness) was designed, developed and characterized by comparing its response against Tissue Equivalent Proportional Counters (TEPCs) in different irradiation fields, showing promising results. Each pixel of the ΔE stage is a thin diode of 9 μm in diameter delimited by a guard ring of 14 μm in diameter. The aim of this work is the study of the charge collection efficiency of the single pixel of the silicon microdosimeter by irradiating a prototype at the micro-beam facility of the Ion Beam Center - IBC of the University of Surrey. Different light ions were exploited (protons, lithium ions and carbon ions) and scanned on different positions on and around a single pixel of the detector. The results show that the charge generated by events on the sensitive region of the ΔE stage is completely collected, while a charge collection efficiency lower than one characterizes the region between the central pixel and its guard ring. The guard ring delimits properly the sensitive region: no signals arise from events outside the 14 μm in diameter ring. Nevertheless, the microdosimetric distributions of the different charged particles highlight a minor distortion in terms of the absorbed dose. This latter result justifies the good agreement with TEPCs in terms of microdosimetric distributions in different hadrons beams described in previous works.

Highlights •The treatment head design implemented in the MC beam model allows the characterization of the secondary spectra radiation. •The beam model is calibrated in absolute dose based on a recent formalism in terms of a Dose-Area-Product within 1.2% •The beam model is validated within clinical constraints including non-isocentric conditions. •33 non-isocentric clinical fields are reproduced within 1% when the average dose gradient is less than 1%/mm. •The model serves as reference for future clinical as well as research work. Abstract 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.

Objective. Experimental determination of beam quality k Q factors for two types of Farmer ionization chambers, NE2571 and IBA FC65-G, in a scanned proton beam for three nominal energies (140 MeV, 180 MeV and 220 MeV) based on water calorimetry. Approach. Beam quality correction factors were determined comparing the results obtained with water calorimetry and ionometry. Water calorimetry was performed to determine the absorbed dose at a depth of measurement in water of 5 g cm−2, limited by the extension of the calorimeter glass vessel used. For the ionometry, two chambers of each type were included in the study. The ionization chambers were calibrated in terms of absorbed dose to water in 60Co at the Swedish Secondary Standard Dosimetry Laboratory, directly traceable to the BIPM, and were used according to the IAEA TRS-398 Code of Practice. Main results. The k Q values determined in the present work have been compared with the values tabulated in TRS-398 and its forthcoming update and also with those obtained in previous water calorimetric measurements and Monte Carlo calculations. All results were found to agree within the combined uncertainties of the different data. Significance. It is expected that the present work will serve as an experimental contribution to k Q -factors for the two chamber types and three scanned proton beam qualities used.

PURPOSE: In all recent protocols for the reference dosimetry of clinical proton beams ionization chamber perturbation factors are assumed to be unity. In this work, such factors were computed using the FLUKA Monte Carlo code for three ionization chamber types, with particular attention to the influence of nuclear interactions. METHODS: The accuracy of the transport algorithms implemented in FLUKA was first evaluated by performing a Fano cavity test. Ionization chamber perturbation factors were computed for the PTW-34001 Roos® and the PTW-34070 and PTW-34073 Bragg peak® chambers for proton beams of 60 to 250 MeV using the same transport parameters that were needed to pass the Fano test. RESULTS: FLUKA was found to pass the Fano test within 0.15%. Ionization chamber simulation results show that the presence of the air cavity and the wall results in dose perturbations of the order of 0.6% and 0.8%, respectively. The perturbation factors are shown to be energy dependent and nuclear interactions must be taken into account for accurate calculation of the ionization chamber's response. CONCLUSION: Ionization chamber perturbations can amount to 1% in high-energy proton beams and therefore need to be considered in dosimetry procedures. This article is protected by copyright. All rights reserved.

Objective. The boundary crossing algorithm available in Geant4 10.07-p01 general purpose Monte Carlo code has been investigated for a 12 and 200 MeV electron source by the application of a Fano cavity test. Approach. Fano conditions were enforced through all simulations whilst varying individual charged particle transport parameters which control particle step size, ionisation and single scattering. Main Results. At 12 MeV, Geant4 was found to return excellent dose consistency within 0.1% even with the default parameter configurations. The 200 MeV case, however, showed significant consistency issues when default physics parameters were employed with deviations from unity of more than 6%. The effect of the inclusion of nuclear interactions was also investigated for the 200 MeV beam and was found to return good consistency for a number of parameter configurations. Significance. The Fano test is a necessary investigation to ensure the consistency of charged particle transport available in Geant4 before detailed detector simulations can be conducted.

The increase in the number of therapeutic proton and ion beam centres worldwide has prompted renewed interest in measuring and simulating microdosimetric spectra in order to help understand the complexity underlying the Relative Biological Effectiveness (RBE) of these treatment modalities. In this context we have studied the capability of the Geant4 toolkit to simulate microdosimetric spectra measured with a Tissue Equivalent Proportional Counter (TEPC) in a clinical carbon ion beam. The simulated spectra were compared with published experimental data obtained along the depth dose curve of a 194 MeV/u carbon beam at the GSI, Darmstadt (Gerlach et al., 2002). The initial beam energy and energy spread employed in the simulation were tuned to match the calculated and measured depth dose distributions. A good agreement was found at all depths after a shift of 4.025 mm was taken into account with agreement for the microdosimetric derived RBE values to within 0.4% and 11.9% for depths 40 and 66 mm in PMMA (Perspex). This work demonstrates that the Geant4 toolkit can accurately reproduce experimental microdosimetric data and can thus be used for independent calculation of lineal energy spectra from which RBE estimates can be derived using the equation of Pihet et al. (1990). The work highlights the difficulty in using experimental work to benchmark Monte Carlo simulations and the need for detailed descriptions of experimental setups used.

Various types of treatment units, such as CyberKnife, TomoTherapy and C-arm linear accelerators (LINACs) are operated using flattening filter free (FFF) photon beams. Their reference dosimetry, however, is currently based on codes of practice that provide data which were primarily developed and tested for high-energy photon beams with flattening filter (WFF). The aim of this work was to introduce equivalent uniform square field sizes of FFF beams to serve as a basis of a unified reference dosimetry procedure applicable to all aforementioned FFF machines. For this purpose, in-house determined experimental data together with published data of the ratio of doses at depths of 20 cm and 10 cm in water (D 20,10) were used to characterize the depth dose distribution of 6 and 10 MV WFF and FFF beams. These data were analyzed for field sizes ranging from 2 × 2 cm2 to 40 × 40 cm2. A scatter function that takes the lateral profiles of the individual beams into account was fitted to the experimental data. The lateral profiles of the WFF beams were assumed to be uniform, while those of the FFF beams were approximated using fourth or sixth order polynomials. The scatter functions of the FFF beams were recalculated using a uniform lateral profile (the same as the physical profile of the WFF beams), and are henceforth denoted as virtual uniform FFF beams (VUFFF). The field sizes of the VUFFF beams having the same scatter contribution as the corresponding FFF beams at a given field size were defined as the equivalent uniform square field (EQUSF) size. Data from four different LINACs with 18 different beams in total, as well as a CyberKnife beam, were analyzed. The average values of EQUSFs over all investigated LINACs of the conventional 10 × 10 cm2 reference fields of 6 MV and 10 MV FFF beams for C-arm LINACs and machine-specific reference fields for CyberKnife and TomoTherapy were 9.5 cm, 9 cm, 5.0 cm and 6.5 cm respectively. The standard deviation of the mean of these EQUSFs was below 0.1 cm. It has been shown that with the introduction of a VUFFF beam, EQUSFs can be consistently defined for a variety of energies and collimations. These EQUSFs can form the basis for a unified reference dosimetry protocol for all different types of FFF machines.

PURPOSE: The IAEA TRS-398 code of practice details the reference conditions for reference dosimetry of proton beams using ionization chambers and the required beam quality correction factors (kQ ). Pencil beam scanning (PBS) systems cannot approximate reference conditions using a single spot. However, dose distributions requested in TRS-398 can be reproduced with PBS using a combination of spots. This study aims to demonstrate, using Monte Carlo (MC) simulations, that kQ factors computed/measured for broad beams can be used with scanned beams for similar reference dose distributions with no additional significant uncertainty. METHODS: We consider the Alfonso formalism13 usually employed for nonstandard photon beams. To approach reference conditions similar as IAEA TRS-398 and the associated dose distributions, PBS must combine many pencil beams with range or energy modulation and shaping techniques that differ from those used in passive systems (broad beams). In order to evaluate the impact of these differences on kQ factors, ionization chamber responses are computed with MC (Geant4 9.6) in three different proton beams, with their corresponding quality factors (Q), producing a 10 × 10 cm2 field with a flat dose distribution for (a) a dedicated scanned pencil beam (Qpbs ), (b) a hypothetical proton source (Qhyp ), and (c) a double-scattering beam (Qds ). The tested ionization chamber cavities are a 2 × 2 × 0.2 mm³ air cavity, a Roos-type ionization chamber, and a Farmer-type ionization chamber. RESULTS AND DISCUSSION: Ranges of Qpbs , Qhyp , and Qds are consistent within 0.4 mm. Flatnesses of dose distributions are better than 0.5%. Calculated kQpbs,Qhypfpbs,fref is 0.999 ± 0.002 for the air cavity and the Farmer-type ionization chamber and 1.001 ± 0.002 for the Roos-type ionization chamber. The quality correction factors kQpbs,Qdsfpbs,fref is 0.999 ± 0.002 for the Farmer-type and Roos-type ionization chambers and 1.001 ± 0.001 for the Roos-type ionization chamber. CONCLUSION: The Alfonso formalism was applied to scanned proton beams. In our MC simulations, neither the difference in the beam profiles (scanned beam vs hypothetical beam) nor the different incident beam energies influenced significantly the beam correction factors. This suggests that ionization chamber quality correction factors in scanned or broad proton beams are indistinguishable within the calculation uncertainties provided dose distributions achieved by both modalities are similar and compliant with the TRS-398 reference conditions.

Based on international reference dosimetry protocols for light-ion beams, a correction factor (k s) has to be applied to the response of a plane-parallel ionisation chamber, to account for recombination of negative and positive charges in its air cavity before these charges can be collected on the electrodes. In this work, k s for IBA PPC40 Roos-type chambers is investigated in four scanned light-ion beams (proton, helium, carbon and oxygen). To take into account the high dose-rates used with scanned beams and LET-values, experimental results are compared to a model combining two theories. One theory, developed by Jaff?, describes the variation of k s with the ionization density within the ion track (initial recombination) and the other theory, developed by Boag, describes the variation of k s with the dose rate (volume recombination). Excellent agreement is found between experimental and theoretical k s-values. All results confirm that k s cannot be neglected. The solution to minimise k s is to use the ionisation chamber at high voltage. However, one must be aware that charge multiplication may complicate the interpretation of the measurement. For the chamber tested, it was found that a voltage of 300 V can be used without further complication. As the initial recombination has a logarithmic variation as a function of 1/V, the two-voltage method is not applicable to these scanned beams.