Evaluation of in vitro irradiation setup: Designed for the horizontal beamline at the Danish Centre for Particle Therapy.

BACKGROUND: Radiobiological experimental setups are challenged by precise sample positioning along depth dose profile, scattering conditions, and practical difficulties that must be addressed in individual designs. The aim of this study was to produce cell survival curves with several irradiation modalities, by using a setup designed at the Danish Centre for Particle Therapy (DCPT) for in vitro proton irradiations using a horizontal beam line and thereby evaluating the setups use for in vitro irradiations experiments. MATERIALS AND METHODS: The setup is a water phantom suitable for in vitro research with multiple irradiation modalities, in particular the pencil scanning proton beam available from a horizontal experimental beamline. The phantom included a water tank of 39.0 × 17.0 × 20.5 cm. Cell survival-curves were produced using the cell line V79 Chinese hamster lung fibroblast cells (V79s) in biological triplicates of clonogenic assays. Cell survival curves were produced with both a 18 MeV electron beam, 6 MV photon beam, and a Spread-Out Bragg Peak (SOBP) proton beam formed by pristine energies of 85-111 MeV where three positions were examined. RESULTS: Survival curves with uncertainty areas were made for all modalities. Dosimetric uncertainty amounted to, respectively, 4%, 3% and 3% for proton, electron, and high energy photon irradiations. Cell survival fraction uncertainty was depicted as the standard deviation between replications of the experiment. CONCLUSION: Cell survival curves could be produced with acceptable uncertainties using this novel water phantom and cellular laboratory workflow. The setup is useful for future in vitro irradiation experiments.

An experimental setup for proton irradiation of a murine leg model for radiobiological studies.

BACKGROUND: The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. METHODS: The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. RESULTS: The dose-response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose-response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. CONCLUSIONS: We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.

Development of an interlaced-crossfiring geometry for proton grid therapy.

BACKGROUND: Grid therapy has in the past normally been performed with single field photon-beam grids. In this work, we evaluated a method to deliver grid therapy based on interlacing and crossfiring grids of mm-wide proton beamlets over a target volume, by Monte Carlo simulations. MATERIAL AND METHODS: Dose profiles for single mm-wide proton beamlets (1, 2 and 3 mm FWHM) in water were simulated with the Monte Carlo code TOPAS. Thereafter, grids of proton beamlets were directed toward a cubic target volume, located at the center of a water tank. The aim was to deliver a nearly homogeneous dose to the target, while creating high dose heterogeneity in the normal tissue, i.e., high gradients between valley and peak doses in the grids, down to the close vicinity of the target. RESULTS: The relative increase of the beam width with depth was largest for the smallest beams (+6.9 mm for 1 mm wide and 150 MeV proton beamlets). Satisfying dose coverage of the cubic target volume (σ < ±5%) was obtained with the interlaced-crossfiring setup, while keeping the grid pattern of the dose distribution down to the target (valley-to-peak dose ratio <0.5 less than 1 cm before the target). Center-to-center distances around 7-8 mm between the beams were found to give the best compromise between target dose homogeneity and low peak doses outside of the target. CONCLUSIONS: A nearly homogeneous dose distribution can be obtained in a target volume by crossfiring grids of mm-wide proton-beamlets, while maintaining the grid pattern of the dose distribution at large depths in the normal tissue, close to the target volume. We expect that the use of this method will increase the tumor control probability and improve the normal tissue sparing in grid therapy.

Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo.

INTRODUCTION: The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP). METHOD: The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. RESULTS: The MDD50 values with 95% confidence intervals were 36.1 (34.2-38.1) Gy for protons in the middle of the SOBP for score 3.5. For 6 MV photons, it was 35.9 (34.5-37.5) Gy and 32.6 (30.7-34.7) Gy for 240 kV photons for score 3.5. The corresponding RBE was 1.00 (0.94-1.05), relative to 6 MV photons and 0.9 (0.85-0.97) relative to 240 kV photons. In the mice group positioned at the SOBP distal dose fall-off, 25% of the mice developed early skin damage compared with 0-8% in other groups. LETd,z = 1 was 8.4 keV/µm at the distal dose fall-off and the physical dose delivered was 7% lower than in the central SOBP position, where LETd,z =1 was 3.3 keV/µm. CONCLUSIONS: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated.

Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation.

INTRODUCTION: Proton beam therapy delivers a more conformal dose distribution than conventional radiotherapy, thus improving normal tissue sparring. Increasing linear energy transfer (LET) along the proton track increases the relative biological effectiveness (RBE) near the distal edge of the Spread-out Bragg peak (SOBP). The severity of normal tissue side effects following photon beam radiotherapy vary considerably between patients. AIM: The dual study aim was to identify gene expression patterns specific to radiation type and proton beam position, and to assess whether individual radiation sensitivity influences gene expression levels in fibroblast cultures irradiated in vitro. METHODS: The study includes 30 primary fibroblast cell cultures from patients previously classified as either radiosensitive or radioresistant. Cells were irradiated at three different positions in the proton beam profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis and angiogenesis. RESULTS: Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated by different radiation qualities. Radiosensitive patient samples had the strongest regulation of gene expression; irrespective of radiation type. CONCLUSIONS: Our findings indicate that the increased LET at the SOBP distal edge position did not generally lead to increased transcriptive response in primary fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy.

Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model.

BACKGROUND: The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. MATERIAL AND METHODS: CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice. RESULTS: The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2-49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69). CONCLUSION: The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models.

Monte Carlo simulations of new 2D ripple filters for particle therapy facilities.

UNLABELLED: At particle therapy facilities with pencil beam scanning, the implementation of a ripple filter (RiFi) broadens the Bragg peak (BP), which leads to fewer energy steps from the accelerator required to obtain an homogeneous dose coverage of the planned target volume (PTV). At the Universitätsklinikum Gießen und Marburg, Germany, a new second generation RiFi has been developed with two-dimensional groove structures. In this work we evaluate this new RiFi design. METHODS: The Monte Carlo (MC) code SHIELD-HIT12A is used to determine the RiFi-induced inhomogeneities in the dose distribution for various ion types, initial particle energies and distances from the RiFi to the phantom surface as well as in the depth of the phantom. The beam delivery and monitor system (BAMS) used at Marburg, the Heidelberg Ionentherapiezentrum (HIT), Universitätsklinikum Heidelberg, Germany and the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany is modeled and simulated. To evaluate the PTV dose coverage performance of the new RiFi design, the heavy ion treatment planning system TRiP98 is used for dose optimization. SHIELD-HIT12A is used to prepare the facility-specific physical dose kernels needed by TRiP, and for recalculating the physical dose distribution after TRiP optimization. RESULTS: At short distances from the RiFi to the phantom surface fine structures in the dose distribution are observed. For various RiFis, ion types and initial particle energies the distance dmax at which maximum dose inhomogeneity occurs is found and an expression for dmax is deduced. The distance d0.01 at which the dose inhomogeneity is less than 1% is estimated and used as a threshold distance at which dose distributions are considered homogeneous. The MC data are found to agree with analytical expressions for dmax and d0.01; both are inversely related to the angular distribution. Increasing scatter from the beam delivery and monitoring system results in reduced dmax and d0.01. Furthermore, dmax and d0.01 are found to be proportional to the RiFi period λ. CONCLUSION: Our findings clearly indicate that the dose inhomogeneity induced by RiFis does not add uncertainties to the dose distribution in the clinical setting. The new RiFi design can be used in treatments to obtain homogeneous PTV dose coverage with fewer energy steps while improving lateral penumbra, thereby reducing the required treatment time.

LET-painting increases tumour control probability in hypoxic tumours.

LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

A method for selection of beam angles robust to intra-fractional motion in proton therapy of lung cancer.

BACKGROUND: Proton therapy offers the potential for sparing the normal tissue surrounding the target. However, due to well-defined proton ranges around the Bragg peak, dose deposition is more sensitive to changes in the water equivalent path length (WEPL) than with photons. In this study, we assess WEPL variations caused by breathing-induced motion for all possible beam angles in a series of lung cancer patients. By studying the association between measures for WEPL variation and breathing-induced target dose degradation we aimed to develop and explore a tool to identify beam angles that are robust to patient-specific patterns of intra-fractional motion. MATERIAL AND METHODS: Using four-dimensional computed tomography (4DCT) images of three lung cancer patients we evaluated the impact of the WEPL changes on target dose coverage for a series of coplanar single-beam plans. The plans were optimised for the internal target volume (ITV) at the maximum intensity projection (MIP) CT for every 3° gantry interval. The plans were transferred to the ten 4DCT phases and the average reduction in ITV V95 over the ten phases, relative to the original MIP CT calculation, was quantified. The target dose reduction was associated with the mean difference between the WEPL and the phase-averaged WEPL computed for all beam rays across all possible gantry-couch angle combinations. RESULTS: The gantry-couch angle maps showed areas of both high and low WEPL variation, with overall quite similar patterns yet with individual differences reflecting differences in tumour position and breathing-induced motion. The coplanar plans showed a strong association between WEPL changes and ITV V95 reduction, with a correlation coefficient ranging between 0.92 and 0.98 for the three patients (p < 0.01). CONCLUSION: We have presented a 4DCT-based method to quantify WEPL changes during the breathing cycle. The method identified proton field gantry-couch angle combinations that were either sensitive or robust to WEPL changes. WEPL variations along the beam path were associated with target under-dosage.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

Novel radiation quality metrics accounting for proton energy spectra for RBE proton models.

BACKGROUND: For proton therapy, a relative biological effectiveness (RBE) of 1.1 is widely applied clinically. However, due to abundant evidence of variable RBE in vitro, and as suggested in studies of patient outcomes, RBE might increase by the end of the proton tracks, as described by several proposed variable RBE models. Typically, the dose averaged linear energy transfer ( LET d $\text{LET}_d$ ) has been used as a radiation quality metric (RQM) for these models. However, the optimal choice of RQM has not been fully explored. PURPOSE: This study aims to propose novel RQMs that effectively weight protons of different energies, and assess their predictive power for variable RBE in proton therapy. The overall objective is to identify an RQM that better describes the contribution of individual particles to the RBE of proton beams. METHODS: High-throughput experimental set-ups of in vitro cell survival studies for proton RBE determination are simulated utilizing the SHIELD-HIT12A Monte Carlo particle transport code. For every data point, the proton energy spectra are simulated, allowing the calculation of novel RQMs by applying different power levels to the spectra of LET or effective Q $Q$ ( Q eff $Q_\mathrm{eff}$ ) values. A phenomenological linear-quadratic-based RBE model is then applied to the in vitro data, using various RQMs as input variables, and the model performance is evaluated by root-mean-square-error (RMSE) for the logarithm of cell surviving fractions of each data point. RESULTS: Increasing the power level, that is, putting an even higher weight on higher LET particles when constructing the RQM is generally associated with an increased model performance, with dose averaged LET 3 $\text{LET}^3$ (i.e., dose averaged cubed LET, cLET d $\mathrm{cLET}_d$ ) resulting in a RMSE value 0.31, compared to 0.45 for a model based on (linearly weighted) LET d $\text{LET}_d$ , with similar trends also observed for track averaged and Q eff $Q_\mathrm{eff}$ -based RQMs. CONCLUSIONS: The results indicate that improved proton variable RBE models can be constructed assuming a non-linear RBE(LET) relationship for individual protons. If similar trends hold also for an in vitro-environment, variable RBE effects are likely better described by cLET d $\mathrm{cLET}_d$ or tracked averaged cubed LET ( cLET t $\mathrm{cLET}_t$ ), or corresponding Q eff $Q_\mathrm{eff}$ -based RQM, rather than linearly weighted LET d $\text{LET}_d$ or LET t $\text{LET}_t$ which is conventionally applied today.

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams.

Objective.This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (LET-) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations.Approach.Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (LET-f) and dose-averaged LET (LET-d) were determined. For both quantities, two sub-types of averages were calculated, either considering the contributions from primary and secondary protons or from all protons and heavier, charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE).Main results.All types ofLET-could be assessed with the luminescence detectors. The experimental determination ofLET-fis in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand,LET-dcan present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from theLET-dcalculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy betweenLET-fandLET-d. Assessment of RBE through the experimentally determinedLET-dvalues agrees with independently acquired reference values, indicating that the investigated detectors can determineLET-with sufficient accuracy for proton therapy.Significance.OSLDs, TLDs, and FNTDs can be used to determineLET-and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived fromLET-, OSLDs and TLDs can simultaneously ascertain dose,LET-, and RBE. This makes passive detectors appealing for measurements in phantoms to facilitate validation of clinical treatment plans or experiments related to proton therapy.

Modeling RBE with other quantities than LET significantly improves prediction of in vitro cell survival for proton therapy.

BACKGROUND: For proton therapy, a relative biological effectiveness (RBE) of 1.1 has broadly been applied clinically. However, as unexpected toxicities have been observed by the end of the proton tracks, variable RBE models have been proposed. Typically, the dose-averaged linear energy transfer (LETd ) has been used as an input variable for these models but the way the LETd was defined, calculated, or determined was not always consistent, potentially impacting the corresponding RBE value. PURPOSE: This study compares consistently calculated LETd with other quantities as input variables for a phenomenological RBE model and attempts to determine which quantity that can best predicts proton RBE. The comparison was performed within the frame of introducing a new model for the proton RBE. METHODS: High-throughput experimental setups of in vitro cell survival studies for proton RBE determination are simulated using the SHIELD-HIT12A Monte Carlo particle transport code. Together with LET, z ∗ 2 / ß 2 $z^{*2}/\beta ^2$ , here called effective Q (Qeff ), and Q are scored. Each quantity is calculated using the dose and track averaging methods, because the scoring includes all hadronic particles, all protons or only primaries. A phenomenological linear-quadratic-based RBE model is subsequently applied to the in vitro data with the various beam quality descriptors used as input variables and the goodness of fit is determined and compared using a bootstrapping approach. Both linear and nonlinear fit functions were tested. RESULTS: Versions of Qeff and Q outperform LET with a statistically significant margin, with the best nonlinear and linear fit having a relative root mean square error (RMSE) for RBE2Gy ± one standard error of 1.55 ± 0.04 (Qeff, t, primary ) and 2.84 ± 0.07 (Qeff, d, primary ), respectively. For comparison, the corresponding best nonlinear and linear fits for LETd, all protons had a relative RMSE of 2.07 ± 0.06 and 3.39 ± 0.08, respectively. Applying Welch's t-test for comparing the calculated RMSE of RBE2Gy resulted in two-tailed p-values of <0.002 for all Q and Qeff quantities compared to LETd, all protons . CONCLUSIONS: The study shows that Q or Qeff could be better RBE descriptors that dose averaged LET.

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams.

Objective.This work investigates the use of Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) detectors to determine both the dose and the radiation quality in light ion beams. The radiation quality is here expressed through either the linear energy transfer (LET) or the closely related metricQeff, which depends on the particle's speed and effective charge. The derived LET andQeffvalues are applied to improve the dosimetry in light ion beams.Approach.OSL detectors were irradiated in mono-energetic1H-,4He-,12C-, and16O-ion beams. The OSL signal is associated with two emission bands that were separated using a pulsed stimulation technique and subjected to automatic corrections based on reference irradiations. Each emission band was investigated independently for dosimetry, and the ratio of the two emission intensities was parameterized as a function of fluence- and dose-averaged LET, as well asQeff. The determined radiation quality was subsequently applied to correct the dose for ionization quenching.Main results.For both materials, theQeffdeterminations in1H- and4He-ion beams are within 5 % of the Monte Carlo simulated values. Using the determined radiation quality metrics to correct the nonlinear (ionization quenched) detector response leads to doses within 2 % of the reference doses.Significance.Al2O3:C and Al2O3:C,Mg OSL detectors are applicable for dosimetry and radiation quality estimations in1H- and4He-ions. Only Al2O3:C,Mg shows promising results for dosimetry in12C-ions. Across both materials and the investigated ions, the estimatedQeffvalues were less sensitive to the ion types than the estimated LET values were. The reduced uncertainties suggest new possibilities for simultaneously estimating the physical and biological dose in particle therapy with OSL detectors.

Initial recombination in the track of heavy charged particles: numerical solution for air filled ionization chambers.

INTRODUCTION: Modern particle therapy facilities enable sub-millimeter precision in dose deposition. Here, also ionization chambers (ICs) are used, which requires knowledge of the recombination effects. Up to now, recombination is corrected using phenomenological approaches for practical reasons. In this study the effect of the underlying dose distribution on columnar recombination, a quantitative model for initial recombination, is investigated. MATERIAL AND METHODS: Jaffé's theory, formulated in 1913 quantifies initial recombination by elemental processes, providing an analytical (closed) solution. Here, we investigate the effect of the underlying charged carrier distribution around a carbon ion track. The fundamental partial differential equation, formulated by Jaffé, is solved numerically taking into account more realistic charge carrier distributions by the use of a computer program (Gascoigne 3D). The investigated charge carrier distributions are based on track structure models, which follow a 1/r(2) behavior at larger radii and show a constant value at small radii. The results of the calculations are compared to the initial formulation and to data obtained in experiments using carbon ion beams. RESULTS: The comparison between the experimental data and the calculations shows that the initial approach made by Jaffé is able to reproduce the effects of initial recombination. The amorphous track structure based charge carrier distribution does not reproduce the experimental data well. A small additional correction in the assessment of the saturation current or charge is suggested by the data. CONCLUSION: The established model of columnar recombination reproduces the experimental data well, whereas the extensions using track structure models do not show such an agreement. Additionally, the effect of initial recombination on the saturation curve (i.e. Jaffé plot) does not follow a linear behavior as suggested by current dosimetry protocols, therefore higher order corrections (such as the investigated ones) might be necessary.

Dose response of alanine detectors irradiated with carbon ion beams.

PURPOSE: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. METHODS: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. RESULTS: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. CONCLUSIONS: The used model and its implementation show a good overall agreement for quasi-monoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

In vitro RBE-LET dependence for multiple particle types.

BACKGROUND: In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize the available data in the literature regarding the dependency of RBE on LET for different particles. METHOD: As RBE is highly dependent on cell type and endpoint, we discriminated the RBE-LET relationship for the three investigated cell lines and at the same endpoint (10% survival in colony formation). Data points were collected from 20, four and four publications for V79, CHO and T1, respectively, in total covering 228 RBE values from a broad range of particle species. RESULTS AND DISCUSSION: All RBE-LET data points demonstrate surprising agreement within the general error band formed by the numerous data points, and display the expected RBE peak at around 100-200 keV/µm. For all three cell lines, the influence of varying the particle type on the RBE was far from obvious, compared to the general experimental noise. Therefore, a dependence of particle type cannot be concluded, and LET alone in fact does seem to be an adequate parameter for describing RBE at 10% survival.

Fluence correction factors and stopping power ratios for clinical ion beams.

BACKGROUND: In radiation therapy, the principal dosimetric quantity of interest is the absorbed dose to water. Therefore, a dose conversion to dose to water is required for dose deposited by ion beams in other media. This is in particular necessary for dose measurements in plastic phantoms for increased positioning accuracy, graphite calorimetry being developed as a primary standard for dose to water dosimetry, but also for the comparison of dose distributions from Monte Carlo simulations with those of pencil beam algorithms. MATERIAL AND METHODS: In the conversion of absorbed dose to phantom material to absorbed dose to water the water-to-material stopping power ratios (STPR) and the fluence correction factors (FCF) for the full charged particle spectra are needed. We determined STPR as well as FCF for water to graphite, bone (compact), and PMMA as a function of water equivalent depth, z(w), with the Monte Carlo code SHIELD-HIT10A. Simulations considering all secondary ions were performed for primary protons as well as carbon, nitrogen and oxygen ions with a total range of 3 cm, 14.5 cm and 27 cm as well as for two spread-out Bragg-peaks (SOBP). STPR as a function of depth are also compared to a recently proposed analytical formula. RESULTS: The STPR are of the order of 1.022, 1.070, and 1.112 for PMMA, bone, and graphite, respectively. STPR vary only little with depth except close to the total range of the ion and they can be accurately approximated with an analytical formula. The amplitude of the FCF depends on the non-elastic nuclear interactions and it is unity if these interactions are turned off in the simulation. Fluence corrections are of the order of a percent becoming more pronounced for larger depths resulting in dose difference of the order of 5% around 25 cm. The same order of magnitude is observed for SOBP. CONCLUSIONS: We conclude that for ions with small total range (z(w-eq) ≤3 cm) dosimetry without applying FCF could in principle be performed in phantoms of materials other than water without a significant loss of accuracy. However, in clinical high-energy ion beams with penetration depths z(w-eq) ≥3 cm, where accurate positioning in water is not an issue, absorbed dose measurements should be directly performed in water or accurate values of FCF need to be established.

Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies.

UNLABELLED: Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields. MATERIAL AND METHODS: Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the University of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. RESULTS: For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. DISCUSSION: Alanine dosimeters, in combination with flux measurements and Monte Carlo calculations with FLUKA, suggest that it is possible to establish a system for monitoring the dose in a mixed neutron and gamma field for BNCT and other applications in radiotherapy.