Pristine Bragg Peak Research Articles

Novel Bragg peak characterization method using proton flux measurements on plastic scintillators

Objective. Bragg peak measurements play a key role in the beam quality assurance in proton therapy. Used as base data for the treatment planning softwares, the accuracy of the data is crucial when defining the range of the protons in the patient.Approach. In this paper a protocol to reconstruct a Pristine Bragg Peak exploring the direct correlation between the particle flux and the dose deposited by particles is presented. Proton flux measurements at the HollandPTC and FLUKA Monte Carlo simulations are used for this purpose. This new protocol is applicable to plastic scintillator detectors developed for Quality Assurance applications. In order to obtain the Bragg curve using a plastic fiber detector, a PMMA phantom with a decoupled and moveable stepper was designed. The step phantom allows to change the depth of material in front of the fiber detector during irradiations. The Pristine Bragg Peak reconstruction protocol uses the measured flux of particles at each position and multiplies it by the average dose obtained from the Monte Carlo simulation at each position.Main results. The results show that with this protocol it is possible to reconstruct the Bragg Peak with an accuracy of about 470µm, which is in accordance with the tolerances set by the AAPM.Significance. It has the advantage to be able to overcome the quenching problem of scintillators in the high ionization density region of the Bragg peak.

Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation part 1: measurement of ionization cluster size distributions

At the Heidelberg Ion-Beam Therapy Center, the track structure of carbon ions of therapeutic energy after penetrating layers of simulated tissue was investigated for the first time. Measurements were conducted with carbon ion beams of different energies and polymethyl methacrylate (PMMA) absorbers of different thicknesses to realize different depths in the phantom along the pristine Bragg peak. Ionization cluster size (ICS) distributions resulting from the mixed radiation field behind the PMMA absorbers were measured using an ion-counting nanodosimeter. Two different measurements were carried out: (i) variation of the PMMA absorber thickness with constant carbon ion beam energy and (ii) combined variation of PMMA absorber thickness and carbon ion beam energy such that the kinetic energy of the carbon ions in the target volume is constant. The data analysis revealed unexpectedly high mean ICS values compared to stopping power calculations and the data measured at lower energies in earlier work. This suggests that in the measurements the carbon ion kinetic energies behind the PMMA absorber may have deviated considerably from the expected values obtained by the calculations. In addition, the results indicate the presence of a marked contribution of nuclear fragments to the measured ICS distributions, especially if the carbon ion does not cross the target volume.

Spread-out Bragg peak measurements using a compact quality assurance range calorimeter at the Clatterbridge cancer centre

Objective. The superior dose conformity provided by proton therapy relative to conventional x-ray radiotherapy necessitates more rigorous quality assurance (QA) procedures to ensure optimal patient safety. Practically however, time-constraints prevent comprehensive measurements to be made of the proton range in water: a key parameter in ensuring accurate treatment delivery. Approach. A novel scintillator-based device for fast, accurate water-equivalent proton range QA measurements for ocular proton therapy is presented. Experiments were conducted using a compact detector prototype, the quality assurance range calorimeter (QuARC), at the Clatterbridge cancer centre (CCC) in Wirral, UK for the measurement of pristine and spread-out Bragg peaks (SOBPs). The QuARC uses a series of 14 optically-isolated 100 × 100 × 2.85 mm polystyrene scintillator sheets, read out by a series of photodiodes. The detector system is housed in a custom 3D-printed enclosure mounted directly to the nozzle and a numerical model was used to fit measured depth-light curves and correct for scintillator light quenching. Main results. Measurements of the pristine 60 MeV proton Bragg curve found the QuARC able to measure proton ranges accurate to 0.2 mm and reduced QA measurement times from several minutes down to a few seconds. A new framework of the quenching model was deployed to successfully fit depth-light curves of SOBPs with similar range accuracy. Significance. The speed, range accuracy and simplicity of the QuARC make the device a promising candidate for ocular proton range QA. Further work to investigate the performance of SOBP fitting at higher energies/greater depths is warranted.

A systematic approach for calibrating a Monte Carlo code to a treatment planning system for obtaining dose, LET, variable proton RBE and out-of-field dose

Objective. While integration of variable relative biological effectiveness (RBE) has not reached full clinical implementation, the importance of having the ability to recalculate proton treatment plans in a flexible, dedicated Monte Carlo (MC) code cannot be understated . Here we provide a step-wise method for calibrating dose from a MC code to a treatment planning system (TPS), to obtain required parameters for calculating linear energy transfer (LET), variable RBE and in general enabling clinical realistic research studies beyond the capabilities of a TPS. Approach. Initially, Pristine Bragg peaks (PBP) were calculated in both the Eclipse TPS and the FLUKA MC code. A rearranged Bortfeld energy-range relation was applied to the initial energy of the beam to fine-tune the range of the MC code at 80% dose level distal to the PBP. The energy spread was adapted by dividing the TPS range by the MC range for dose level 80%–20% distal to the PBP. Density and relative proton stopping power were adjusted by comparing the TPS and MC for different Hounsfield units. To find the relationship of dose per primary particle from the MC to dose per monitor unit in the TPS, integration was applied to the area of the Bragg curve. The calibration was validated for spread-out Bragg peaks (SOBP) in water and patient treatment plans. Following the validation, variable RBE were calculated using established models. Main results. The PBPs ranges were within ± mm threshold, and a maximum of 5.5% difference for the SOBPs was observed. The patient validation showed excellent dose agreement between the TPS and MC, with the greatest differences for the lung tumor patient. Significance. A procedure for calibrating a MC code to a TPS was developed and validated. The procedure enables MC-based calculation of dose, LET, variable RBE, advanced (secondary) particle tracking and more from treatment plans.

A Molecular Approach to Characterize the Effects of Fluence, Fluence Rate and LET on Radiation Damage

Effects of fluence, fluence rate and LET on radiation damage are not resolved using traditional methods of measuring energy deposited by ionization events. The deficiency led to the use of empirical RBE factors in the clinical applications of particle therapy. The use of ionization dosimetry is similarly challenged when applied to development of radiation treatment at ultrahigh (FLASH) dose rate. This study reports a molecular method using plasmid DNA as a more comprehensive model for radiation dosimetry than ionization measurements. Aqueous solutions of purified supercoiled plasmid DNA, pUC19 (2686 bp), were prepared at different scavenging conditions and injected into 5x5x1 mm3 wells as detector elements. Irradiated samples were analyzed using base excision repair enzymes (Nth and Fpg) and gel electrophoresis to measure yields for DNA single and double strand breaks (SSB and DSB), and clustered lesions. The low LET characteristics of conventional radiation treatment was modeled using orthovoltage 150 kVp x-rays to deliver 2-110 Gy at 90 and 0.5 Gy/s. Higher LET irradiations in the range of 2 - 14 keV/μm were facilitated by measurements in the pristine Bragg peak region using synchrotron-produced 142.2 MeV protons to deliver dose at 2 - 160 Gy at 600 and 1 Gy/s. The DNA wells were inserted into a solid water equivalent phantom for proton irradiation. Only 4 wells could be positioned in the short Bragg peak region in water (∼ 2 cm). To alleviate the uncertainties due to rapidly varying dose and LET distributions, we innovated the use of a 3% water density (i.e., Styrofoam) medium to extend the Bragg peak region from 2 cm to 20 cm, enabling the placement of 20 well containers. Quantity and quality of molecular damage in the plasmid DNA model varies with fluence, fluence rate and LET of radiation. At high fluence (> 30 Gy) of low-LET radiations, the yields of DNA SSB and non-DSB clustered lesions depend on the fluence rate. These yields decrease by two times between ultrahigh and conventional dose rate irradiation. At a given fluence and fluence rate, the yields for the formation of DNA DSB and non-DSB clustered lesions increase linearly with LET. The low-density phantom allows significant (∼ 10 folds) increase in the number of sampling points and more accurate sample positioning at specific LET compared to water-equivalent phantom. Monte-Carlo track structure simulation of yields for different DNA lesions is being developed to model the molecular damage. In parallel, approaches to improve the sensitivity of the measurements to dose are being investigated. Our results suggest that a molecular-based approach can be used to differentiate the effects of fluence, fluence rate, and LET on radiation damage. The approach demonstrates the potential to improve on the modeling of radiation effects in biological systems than using measured ionization energy. Correlation of the molecular changes to biological outcome for in vitro and in vivo systems are under investigation.

Development and validation of MonteRay, a fast Monte Carlo dose engine for carbon ion beam radiotherapy.

Monte Carlo (MC) simulations are considered the gold-standard for accuracy in radiotherapy dose calculation; so far however, no commercial treatment planning system (TPS) provides a fast MC for supporting clinical practice in carbon ion therapy. To extend and validate the in-house developed fast MC dose engine MonteRay for carbon ion therapy, including physical and biological dose calculation. MonteRay is a CPU MC dose calculation engine written in C++ that is capable of simulating therapeutic proton, helium and carbon ion beams. In this work, development steps taken to include carbon ions in MonteRay are presented. Dose distributions computed with MonteRay are evaluated using a comprehensive validation dataset, including various measurements (pristine Bragg peaks, spread out Bragg peaks in water and behind an anthropomorphic phantom) and simulations of a patient plan. The latter includes both physical and biological dose comparisons. Runtimes of MonteRay were evaluated against those of FLUKA MC on a standard benchmark problem. Dosimetric comparisons between MonteRay and measurements demonstrated good agreement. In terms of pristine Bragg peaks, mean errors between simulated and measured integral depth dose distributions were between -2.3% and +2.7%. Comparing SOBPs at 5, 12.5 and 20cm depth, mean absolute relative dose differences were 0.9%, 0.7% and 1.6% respectively. Comparison against measurements behind an anthropomorphic head phantom revealed mean absolute dose differences of with global 3%/3mm 3D-γ passing rates of 99.3%, comparable to those previously reached with FLUKA (98.9%). Comparisons against dose predictions computed with the clinical treatment planning tool RayStation 11B for a meningioma patient plan revealed excellent local 1%/1mm 3D-γ passing rates of 98% for physical and 94% for biological dose. In terms of runtime, MonteRay achieved speedups against reference FLUKA simulations ranging from 14× to 72×, depending on the beam's energy and the step size chosen. Validations against clinical dosimetric measurements in homogeneous and heterogeneous scenarios and clinical TPS calculations have proven the validity of the physical models implemented in MonteRay. To conclude, MonteRay is viable as a fast secondary MC engine for supporting clinical practice in proton, helium and carbon ion radiotherapy.

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

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

Carbon-Ion Therapy Patient-Specific QA: Preliminary Results Derived Using 3D Polymer Gel Dosimetry in Anthropomorphic Inhomogeneous Geometry

<h3>Purpose/Objective(s)</h3> Improved conformity in carbon-ion radiation therapy (CIRT) with respect to photon RT comes at the cost of a potential reduced delivery robustness due to patient setup uncertainties, approximations in dose calculations and carbon-ion range uncertainties. This work presents preliminary results of a study aiming to address these challenges using 3D polymer gel dosimetry in anthropomorphic and inhomogeneous geometry. <h3>Materials/Methods</h3> All irradiations were performed at a synchrotron facility, in one of the treatment rooms equipped with a horizontal fixed beam line and pencil beam scanning (PBS) modality. For basic dosimetric characterization, carbon pristine Bragg peaks (BP) (ranges 30, 70, 90 mm in water) and a spread-out BP (SOBP) (range 115 mm and modulation 40 mm) were delivered on a cylindrical PMMA container filled with VIPAR polymer gel. An anthropomorphic phantom equipped with a cylindrical polymer gel insert was used for the irradiation of a pseudo-clinical CIRT plan, following all the steps of the standard clinical workflow, from simulation CT to irradiation. Two contralateral beams were optimized with a TPS (v.8b) to deliver 15 Gy (RBE) on a target located approximately at the center of the brain, in proximity of critical OARs such as brainstem and optical pathways. The phantom was then MRI scanned post-irradiation to retrieve the irradiated brain volume in 3D. The measured irradiated volume was compared against corresponding TPS derived data. <h3>Results</h3> Carbon-ion range was spatially verified with an accuracy of < 1 mm. For both the pristine BP and the SOBP irradiations. A significant deviation of the polymer gels' response on high-LET has been observed, as expected from previous studies with proton irradiations. For the pseudo-clinical treatment plan, a qualitative comparison between doses measured in polymer gels, against the corresponding TPS calculations, revealed a satisfying geometric accuracy of dose delivery in 3D, thus showing a high 3D geometrical accuracy of dose delivery in a typical standard clinical workflow. <h3>Conclusion</h3> In this work, we showed that patient-specific 3D polymer gel dosimetry is applicable to CIRT, as a valid tool to evaluate dosimetric and spatial plan accuracy in the clinical environment. As expected, the LET dependence of polymer gel's response, especially in the high-LET region, poses severe limitations for accurate dose measurements. Nevertheless, the proposed methodology is a promising efficient and safe clinical way for verifying such a complex RT technique.

Dose Rate Control of FLASH Proton Beam for Animal Testing: Monte Carlo Simulation

<h3>Purpose/Objective(s)</h3> Compared to conventional proton therapy (PT), ultra-high dose rate (FLASH) PT can reduce the toxicity to normal tissues while maintaining tumor control. The biological effect of FLASH beam will depend on its dose rate. In this study, we proposed a method that can freely change the dose rate of FLASH proton beam and deliver its uniform dose to mice for animal testing. <h3>Materials/Methods</h3> A FLASH proton beam nozzle was built in our proton therapy system for animal experiments. Ultra-high dose rate higher than 200 Gy/s can be obtained at the plateau region in the pristine Bragg peak of 230 MeV, 300 nA proton beam. The nozzle consisted of two main parts: a graphite scatterer that provides a uniform dose distribution from a Gaussian proton beam with ultra-high dose rate and a lead scatterer that can control the dose rate of the FLASH proton beam. A variable collimator system and an animal irradiation stage were added for the study of FLASH effects. The graphite scatterer was designed to obtain a uniform dose distribution with a size of 2 cm without reducing the dose rate significantly. It had a Gaussian shape and was installed downstream of a window extracting proton beam into the air. The lead scatterer was designed to control the dose rate of proton beam by changing its thickness and position. Its position was adjustable from 10 to 50 cm from the isocenter. It had a flat plate shape and was installed at the end of the proton beam nozzle. The graphite scatterer is slidable and the lead scatterer is detachable not to interfere with the existing nozzles. The dose rates and lateral dose profiles were calculated using a simulation toolkit. <h3>Results</h3> A FLASH proton beam nozzle was designed to control the dose rate under the ultra-high dose rate condition and to partially irradiate a mouse with uniform dose. Dose rates exceeding 40 Gy/s for 230 MeV proton beam were obtained at the plateau region in the pristine Bragg peak. The dose rate could be changed from 100 to 44 Gy/s, and the field size with ±10% dose uniformity was about 2 cm. <h3>Conclusion</h3> Our FLASH proton beam nozzle can conduct animal testing on the flash effect without interfering with existing proton beam nozzle. In addition, various studies of the FLASH effect depending on dose rate became possible. This approach designing a FLASH proton beam nozzle may be applicable to other proton therapy facilities. In the near future, animal experiments to demonstrate the FLASH effect will follow in our institute.

Determination of the proton LET using thin film solar cells coated with scintillating powder.

The amount of luminescent light detected in a scintillator is reduced with increased proton linear energy transfer (LET) despite receiving the same proton dose, through a phenomenon called quenching. This study evaluated the ability of a solar cell coated with scintillating powder (SC-SP) to measure therapeutic proton LET by measuring the quenching effect of the scintillating powder using a solar cell while simultaneously measuring the dose of the proton beam. SC-SP was composed of a flexible thin film solar cell and scintillating powder. The LET and dose of the pristine Bragg peak in the 14 cm range were calculated using a validated Monte Carlo model of a double scattering proton beam nozzle. The SC-SP was evaluated by measuring the proton beam under the same conditions at specific depths using SC-SP and Markus chamber. Finally, the 10 and 20 cm range pristine Bragg peaks and 5 cm spread-out Bragg peak (SOBP) in the 14 cm range were measured using the SC-SP and the Markus chamber. LETs measured using the SC-SP were compared with those calculated using Monte Carlo simulations. The quenching factors of the SC-SP and solar cell alone, which were slopes of linear fit obtained from quenching correction factors according to LET, were 0.027 and 0.070 µm/keV (R2 : 0.974 and 0.975). For pristine Bragg peaks in the 10 and 20 cm ranges, the maximum differences between LETs measured using the SC-SP and calculated using Monte Carlo simulations were 0.5 keV/µm (15.7%) and 1.2 keV/µm (12.0%), respectively. For a 5 cm SOBP proton beam, the LET measured using the SC-SP and calculated using Monte Carlo simulations differed by up to 1.9 keV/µm (18.7%). Comparisons of LETs for pristine Bragg peaks and SOBP between measured using the SC-SP and calculated using Monte Carlo simulations indicated that the solar cell-based system could simultaneously measure both LET and dose in real-time and is cost-effective.

Linear energy transfer (LET) spectroscopy and relative biological effect estimation by SiC-based dosimeter at clinical carbon-beam cancer therapy field

A radiation-tolerant silicon carbide (SiC) based dosimeter was developed for the measurement of linear energy transfer (LET) distributions along the Bragg curve for pristine and spread-out Bragg peak (SOBP) clinical carbon beam. Since the conventional ionized chamber is not suitable and effective for LET measurement, several energy-dispersive dosimeters are being developed and tested in the clinical field. While most of the detector lacks radiation hardness against carbon beam, we have utilized wide-bandgap semiconductors of SiC with different epitaxial layers from 25, 69, and 170 μm as a dosimeter for the clinical carbon field at Gunma University Heavy Ion Medical Center (GHMC). LET spectra were obtained not only for pristine carbon beams with an energy of 290 MeV/n but also SOBP conditions. It was confirmed through the changes in LET distribution, primally carbons and fragments are identified, and those energy depositions are successfully obtained by the fabricated SiC dosimeter. The distribution of relative biological effectiveness (RBE) was estimated from LET through biological estimation models. Results suggested that SiC-based dosimeter is successful in being utilized in the detailed characterization of the clinical carbon therapy field.

Decomposition of the weight fractions for modelling ridge filters in a proton wobbling nozzle

In proton therapy, the width of a pristine Bragg peak is too narrow to cover the entire tumor volume, and should be spread out using the Spread out Bragg peak (SOBP) techniques such as energy stacking, range modulator wheel and ridge filter. The main purpose of this study was to demonstrate feasibility of using a simple least square technique to decompose the simulated weight fractions of elemental Bragg peaks of ridge filters used in a clinical wobbling beam nozzle. First, initial simulated beam parameters including mean energy and energy spread at the nozzle entrance for all available clinical energies were commissioned against measurements for the open middle wobbling field at the Proton and Radiation Center of the Linkou Chang Gung Memorial Hospital (LCGMH) using the Particle Therapy Simulation Framework (PTSim) Monte Carlo package. Material composition and geometry of nozzle components were provided by the vendor. Depth dose distribution of beam energies from 70 to 230 MeV at 20-MeV increment were simulated and validated with measurement. Curve fitting to those beam parameters was performed to extend simulation energy range to all available clinical energies. For the reconstructed ridge filter simulation, elemental Bragg peaks (BPs) with layer filters corresponding to ridge filter step thicknesses were obtained as bases of the weight factor decomposition. The least square technique was implemented to decompose weight factors for individual ridge filter at a selected beam energy within its applicable energy range. Finally, the reconstructed ridge filters using decomposed weight factors were tested at one other energy to validate the study design. Four different ridge filters (5 cm-LE, 5 cm-HE, 10 cm and 11 cm SOBP) were examined in this study. Commission results for tuned beam parameter settings showed maximum disagreement of BP characteristics, represented by the 80% dose depth (R80d) and width of distal fall-off (W80-20), occurred at 230 MeV and was smaller than 0.2 and 0.5 mm respectively. Furthermore, analyzed outcome for SOBPs from the four ridge filters revealed general improvement of agreement to measurement with decomposition and satisfactory agreement between measurements and those with least square technique. Deviation from measurement of SOBP characteristics evaluated for R90d, W80-20 and SOBP flatness after weight decomposition showed values smaller than 1mm/1%. Similar evaluation of SOBP width generated larger difference with maximum value of 2.7 mm for the 11-cm ridge filter. Results of the validation testes were similar with maximum deviation of 1.4 mm, 0.6 mm, 0.2% and 3.8 mm for R90d, W80-20, flatness and width respectively.

Technical note: Evaluation and second check of a commercial Monte Carlo dose engine for small-field apertures in pencil beam scanning proton therapy.

To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small-field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a second check for RayStation MC. We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in-water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5cm and either 2cm or 4cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a second check tool, 10 small-field (average target volume 8.3 cm3 ) patient treatment plans were calculated by each dose engine followed by a statistical comparison. Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by -1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in-water film measurements, RayStation MC and MCsquare both performed well with an average 2D-3D gamma passing rate of 99.4% and 99.7% (3%/3mm), respectively. A t-test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over 10 patients resulted in an average 3D-3D gamma passing rates of 98.5% (3%/3mm) and 94.1% (2%/2mm), respectively. The validity of RayStation MC algorithm for use with patient-specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate second check of RayStation MC in this scenario.

Demonstration of an optically stimulated luminescence (OSL) material with reduced quenching for proton therapy dosimetry: MgB4O7:Ce,Li

The objective of this work is to demonstrate that MgB4O7:Ce,Li, a new optically stimulated luminescence (OSL) dosimetric material, shows improved response for proton therapy dosimetry, with less reduction in luminescence detector efficiency with the particle linear energy transfer (LET). MgB4O7:Ce,Li was synthesized and its luminescence efficiency as a function of LET was characterized for dose-averaged LET values from 0.73 keV/μm up to 74.9 keV/μm using proton, 4He, and 12C ion beams. Commercial Al2O3:C OSLDs were also used for comparison. Monte Carlo simulations were used to predict the material's response in pristine and spread-out Bragg peaks (SOBP), suggesting the MgB4O7:Ce,Li would offer minimum quenching in proton beams of energies relevant to radiotherapy. This prediction was confirmed by irradiations of MgB4O7:Ce,Li and Al2O3:C along SOBPs from proton beams. The results demonstrate that new OSL materials optimized for proton dosimetry can be developed using their dose response to low-LET radiation as a guide during material development.

Assessment of secondary neutrons in particle therapy by Monte Carlo simulations

Objective. The purpose of this study is to estimate the energy and angular distribution of secondary neutrons inside a phantom in hadron therapy, which will support decisions on detector choice and experimental setup design for in-phantom secondary neutron measurements. Approach. Dedicated Monte Carlo simulations were implemented, considering clinically relevant energies of protons, helium and carbon ions. Since scored quantities can vary from different radiation transport models, the codes FLUKA, TOPAS and MCNP were used. The geometry of an active scanning beam delivery system for heavy ion treatment was implemented, and simulations of pristine and spread-out Bragg peaks were carried out. Previous studies, focused on specific ion types or single energies, are qualitatively in agreement with the obtained results. Main results. The secondary neutrons energy distributions present a continuous spectrum with two peaks, one centred on the thermal/epithermal region, and one on the high-energy region, with the most probable energy ranging from 19 up to 240 MeV, depending on the ion type and its initial energy. The simulations show that the secondary neutron energies may exceed 400 MeV and, therefore, suitable neutron detectors for this energy range shall be needed. Additionally, the angular distribution of the low energy neutrons is quite isotropic, whereas the fast/relativistic neutrons are mainly scattered in the down-stream direction. Significance. It would be possible to minimize the influence of the heavy ions when measuring the neutron-generated recoil protons by selecting appropriate measurement positions within the phantom. Although there are discrepancies among the three Monte Carlo codes, the results agree qualitatively and in order of magnitude, being sufficient to support further investigations with the ultimate goal of mapping the secondary neutron doses both in- and out-of-field in hadrontherapy. The obtained secondary neutron spectra are available as supplementary material.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PurposeEye‐dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed.Material/MethodsThe HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye‐dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in‐house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)‐398 Code of Practice for absolute dose measurement, and the IAEA TRS‐398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread‐out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor‐specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated.ResultsA pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall‐offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2, and 0.80 mm, respectively. Average distal fall‐offs of the HollandPTC eyeline were 0.20 g/cm2, and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source‐to‐axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165–350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%.ConclusionsHollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation‐related toxicities. This interinstitutional comparison could support further research on ocular post‐PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Spread-out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization.

The purpose of this work is to (a) demonstrate the feasibility of delivering a spread-out Bragg peak (SOBP) proton beam in ultra-high dose rate (FLASH) using a proton therapy synchrocyclotron as a major step toward realizing an experimental platform for preclinical studies, and (b) evaluate the response of four models of ionization chambers in such a radiation field. A clinical Mevion HYPERSCAN® synchrocyclotron was adjusted for ultra-high dose rate proton delivery. Protons with nominal energy of 230MeV were delivered in pulses with temporal width ranging from 12.5μs to 24μs spanning from conventional to FLASH dose rates. A boron carbide absorber and a range modulator block were placed in the beam path for range modulation and creating an SOBP dose profile. The radiation field was defined by a brass aperture with 11mm diameter. Two Faraday cups were used to determine the number of protons per pulse at various dose rates. The dosimetric response of two cylindrical (IBA CC04 and CC13) and two plane-parallel (IBA PPC05 and PTW Advanced Markus® ) ionization chambers were evaluated. The dose rate was measured using the plane-parallel ionization chambers. The integral depth dose (IDD) was measured with a PTW Bragg Peak® ionization chamber. The lateral beam profile was measured with EBT-XD radiochromic film. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements and as a tool for further optimization of the range modulators' design. Faraday cups measurement showed that the maximum protons per pulse is 39.9 pC at 24μs pulse width. A good agreement between the measured and simulated IDD and lateral beam profiles was observed. The cylindrical ionization chambers showed very high ion recombination and deemed not suitable for absolute dosimetry at ultra-high dose rates. The average dose rate measured using the PPC05 ionization chamber was 163Gy/s at the pristine Bragg peak and 126Gy/s at 1cm depth for the SOBP beam. The SOBP beam range and modulation were measured 24.4mm and 19mm, respectively. The pristine Bragg peak beam had 25.6mm range. Simulation results showed that the IDD and profile flatness can be improved by the cavity diameter of the range modulator and the number of scanned spots, respectively. Feasibility of delivering protons in an SOBP pattern with >100Gy/s average dose rate using a clinical synchrocyclotron was demonstrated. The dose heterogeneity can be improved through optimization of the range modulator and number of delivered spots. Plane-parallel chambers with smaller gap between electrodes are more suitable for FLASH dosimetry compared to the other ion chambers used in this work.

Applications of a novel detector for pencil beam scanning proton therapy beam quality assurance

This study utilized a new type of detector, the CROSS II (Liverage Biomedical Inc., Taiwan), to perform a beam quality assurance (QA) procedure on a Sumitomo (Sumitomo Heavy Industries, Inc., Japan) pencil beam linear scanning proton therapy machine. The Cross II can monitor proton Pristine Bragg peak range, beam width, beam size, beam position, and scanning speed. All the data presented here were collected during a time span of over one year. The accuracy of the QA program could be verified if all the QA items were tested stably and within the programmed tolerances. Our results showed that the proton range remained within the [Formula: see text] mm tolerance, with the majority of measurements within [Formula: see text] mm, [Formula: see text] mm for spot size, 1.5 mm for spot position, and [Formula: see text]% for scanning speed. We found that the CROSS II detector is in high precise and steady state with highly efficient. Our proton therapy system was also proven to be in an accurate and reliable condition according to our QA results.

18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro.

PurposeProton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of 18O to 18F in an 18O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy.Materials and MethodsReported here is a feasibility study with a therapeutic proton beam used to irradiate H218O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an 18F decay signal with T1/2 of ∼111 minutes.ResultsThe 18O to 18F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic 18O-thymidine concentrations of 5 μM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2.ConclusionsThese data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of 18O to 18F in substituted thymidine enabling proton radiation enhancement in a cancer cell. 18O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.

Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle. The main components from the IBA nozzle were implemented in the FLUKA MC code. We calibrated and verified the following entities to experimental measurements: range of pristine Bragg peaks (PBPs) and spread-out Bragg peaks (SOBPs), energy spread, lateral profiles, compensator range degradation, and absolute dose. We recalculated two patients with different field setups, comparing FLUKA vs. treatment planning system (TPS) dose, also obtaining LET and variable RBE doses. We achieved good agreement between FLUKA and measurements. The range differences between FLUKA and measurements were for the PBPs within ±0.9 mm (83% ⩽ 0.5 mm), and for SOBPs ±1.6 mm (82% ⩽ 0.5 mm). The differences in modulation widths were below 5 mm (79% ⩽ 2 mm). The differences in the distal dose fall off (D80%–D20%) were below 0.5 mm for all PBPs and the lateral penumbras diverged from measurements by less than 1 mm. The mean dose difference (RBE = 1.1) in the target between the TPS and FLUKA were below 0.4% in a three-field plan and below 1.4% in a four-field plan. A dose increase of 9.9% and 7.2% occurred when using variable RBE for the two patients, respectively. We presented a method to recalculate DS proton plans in the FLUKA MC code. The implementation was used to obtain LET and variable RBE dose and can be used for investigating variable RBE for previously treated patients.