Spread-out Bragg Peak Research Articles

Impact of air gap, range shifter, and delivery technique on skin dose in proton therapy.

Side effects of radiation therapy may include skin damage. The surface dose is of great interest and contains the buildup effect. In particular, the proton therapy community requires further experimental data to quantify doses in the surface region. This specification includes the skin dose, which is defined according to ICRU Report No. 39 at 70μm water equivalent depth. The aim of this study is to gather more knowledge of the skin dose by varying key parameters defined by the patient treatment plan. This consists of clinical aspects such as the influence of the air gap, the application of a range shifter (RS), or the proton delivery technique. Skin doses were determined with a PTW 23391 extrapolation chamber with three thin Kapton® entrance windows operated as a conventional ionization chamber. The impact on the skin dose for quasi-monoenergetic pencil beam scanning (PBS) proton beams was evaluated for clinical air gaps between 3.5 and 51.1cm. The differences in skin dose were assessed by irradiating equivalent fields with an RS of 51mm water equivalent thickness (RS51) and without. Furthermore, the delivery techniques PBS, uniform scanning (US), and double scattering (DS) were compared by defining a spread-out Bragg peak (SOBP). TOPAS (V.3.1.2) was used to model an IBA nozzle with PBS and to score dose to water at the surface of a water phantom. For the monoenergetic fields without the application of the RS the skin dose was constant down to an air gap of 6.2cm. A lower air gap of 3.5cm showed a variation in skin dose by up to 2.4% compared to the results obtained with larger air gaps. With the inserted RS51 an increase in the skin dose was found for air gaps smaller than 11.3cm. Experimentally, a dose difference of 1.4% was recorded for an air gap of 6.2cm by inserting an RS and none. With the Monte Carlo calculations the largest dose increase was observed at the air gap of 3.5cm with 1.7% and 4.0% relative to the skin dose results without the RS and to the largest evaluated air gap of 51.1cm, respectively. The SOBP comparison of the beam modalities at the measuring plane at the isocenter revealed higher skin doses without RS (including RS) by up to +1.9% (+1.5%) for DS and +1.3% (+1.1%) for US compared to PBS. For all three techniques an approx. 2% rise in skin dose was observed for the largest evaluated air gap of 37.7cm to an air gap of 6.2cm when using an RS51. The study investigated aspects of skin dose of a water equivalent phantom by varying key parameters of a proton treatment plan. Parameters like the RS, the air gap, and the delivery modality have an impact on the order of 4.0% for the skin dose at the depth of 70μm. The increases in skin dose are the effects of the contribution of the increased electron fluence at small air gaps and the emitted hadronic particles produced by the RS.

Variance-based sensitivity analysis for uncertainties in proton therapy: A framework to assess the effect of simultaneous uncertainties in range, positioning, and RBE model predictions on RBE-weighted dose distributions.

Treatment plans in proton therapy are more sensitive to uncertainties than in conventional photon therapy. In addition to setup uncertainties, proton therapy is affected by uncertainties in proton range and relative biological effectiveness (RBE). While to date a constant RBE of 1.1 is commonly assumed, the actual RBE is known to increase toward the distal end of the spread-out Bragg peak. Several models for variable RBE predictions exist. We present a framework to evaluate the combined impact and interactions of setup, range, and RBE uncertainties in a comprehensive, variance-based sensitivity analysis (SA). The variance-based SA requires a large number (104 -105 ) of RBE-weighted dose (RWD) calculations. Based on a particle therapy extension of the research treatment planning system CERR we implemented a fast, graphics processing unit (GPU) accelerated pencil beam modeling of patient and range shifts. For RBE predictions, two biological models were included: The mechanistic repair-misrepair-fixation (RMF) model and the phenomenological Wedenberg model. All input parameters (patient position, proton range, RBE model parameters) are sampled simultaneously within their assumed probability distributions. Statistical formalisms rank the input parameters according to their influence on the overall uncertainty of RBE-weighted dose-volume histogram (RW-DVH) quantiles and the RWD in every voxel, resulting in relative, normalized sensitivity indices (S=0: noninfluential input, S=1: only influential input). Results are visualized as RW-DVHs with error bars and sensitivity maps. The approach is demonstrated for two representative brain tumor cases and a prostate case. The full SA including RWD calculations took 39, 11, and 55min, respectively. Range uncertainty was an important contribution to overall uncertainty at the distal end of the target, while the relatively smaller uncertainty inside the target was governed by biological uncertainties. Consequently, the uncertainty of the RW-DVH quantile D98 for the target was governed by range uncertainty while the uncertainty of the mean target dose was dominated by the biological parameters. The SA framework is a powerful and flexible tool to evaluate uncertainty in RWD distributions and DVH quantiles, taking into account physical and RBE uncertainties and their interactions. The additional information might help to prioritize research efforts to reduce physical and RBE uncertainties and could also have implications for future approaches to biologically robust planning and optimization.

Semianalytical tool for spread-out Bragg peak optimization in an active energy-modulation proton therapy linac

Intensity Modulated Proton Therapy (IMPT) can take great advantage of fast tools based on analytical or semianalytical approaches providing dose evaluation in a target. Here, a semianalytical method is described that has been developed for the TOP-IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTherapy) accelerator, consisting of a pulsed full linear accelerator for proton therapy being developed at ENEA Frascati, where preliminary tests of active beam energy and intensity modulation are undergoing. The method relies on a two-step procedure that provides the main accelerator parameters and optimizes the number and the weights of the energetic components needed to obtain a uniform Spread-Out Bragg Peak (SOBP) in the target region. In the present paper, the theoretical basis of the method is described in detail together with two practical example applications.

Dose quantification in carbon ion therapy using in-beam positron emission tomography

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

Monte Carlo implementation of new algorithms for the evaluation of averaged-dose and -track linear energy transfers in 62 MeV clinical proton beams

We exploited the power of the Geant4 Monte Carlo toolkit to study and validate new approaches for the averaged linear energy transfer (LET) calculation in 62 MeV clinical proton beams. The definitions of the averaged LET dose and LET track were extended, so as to fully account for the contribution of secondary particles generated by target fragmentation, thereby leading to a more general formulation of the LET total. Moreover, in the proposed new strategies for the LET calculation, we minimised the dependencies in respect to the transport parameters adopted during the Monte Carlo simulations (such as the production cut of secondary particles, voxel size and the maximum steplength). The new proposed approach was compared against microdosimetric experimental spectra of clinical proton beams, acquired at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) from two different detectors: a mini-tissue equivalent proportional chamber (TEPC), developed at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN) and a silicon-on-insulator (SOI) microdosimeter with 3D sensitive volumes developed by the Centre for Medical Radiation Physics of Wollongong University (CMRP-UoW). A significant increase of the LET in the entrance region of the spread out Bragg peak (SOBP) was observed, when the contribution of the generated secondary particles was included in the calculation. This was consistent with the experimental results obtained.

FLUKA simulation of target fragmentation in proton therapy.

In proton therapy, secondary fragments are created in nuclear interactions of the beam with the target nuclei. The secondary fragments have low kinetic energies and high atomic numbers as compared to primary protons. Fragments have a high LET and deposit all their energy close to the generation point. For their characteristics, secondary fragments can alter the dose distribution and lead to an increase of RBE for the same delivered physical dose. Moreover, the radiobiological impact of target fragmentation is significant mostly in the region before the Bragg peak, where generally healthy tissues are present, and immediately after Bragg peak. Considering the high biological impact of those particles, especially in the case of healthy tissues or organs at risk, the inclusion of target fragmentation processes in the dose calculation of a treatment planning system can be relevant to improve the treatment accuracy and for this reason it is one of the major tasks of the MoVe IT project. In this study, Monte Carlo simulations were employed to fully characterize the mixed radiation field generated by target fragmentation in proton therapy. The dose averaged LET has been evaluated in case of a Spread Out Bragg Peak (SOBP). Starting from LET distribution, RBE has been evaluated with two different phenomenological models. In order to characterize the mixed radiation field, the production cross section has been evaluated by means of the FLUKA code. The future development of present work is to generate a MC database of fragments fluence to be included in TPS.

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.

Evaluations of a flat-panel based compact daily quality assurance device for proton pencil beam scanning (PBS) system.

To evaluate the flat-panel detector quenching effect and clinical usability of a flat-panel based compact QA device for PBS daily constancy measurements. The QA device, named Sphinx Compact, is composed of a 20x20 cm2 flat-panel imager mounted on a portable frame with removable plastic modules for constancy checks of proton energy (100MeV, 150MeV, 200MeV), Spread-Out-Bragg-Peak (SOBP) profile, and machine output. The potential quenching effect of the flat-panel detector was evaluated. Daily PBS QA tests of X-ray/proton isocenter coincidence, the constancy of proton spot position and sigma as well as the energy of pristine proton beam, and the flatness of SOBP proton beam through the 'transformed' profile were performed and analyzed. Furthermore, the sensitivity of detecting energy changes of pristine proton beam was also evaluated. The quenching effect was observed at depths near the pristine peak regions. The flat-panel measured range of the distal 80% is within 0.9mm to the defined ranges of the delivered proton beams. X-ray/proton isocenter coincidence tests demonstrated maximum mismatch of 0.3mm between the two isocenters. The device can detect 0.1mm change of spot position and 0.1MeV energy changes of pristine proton beams. The measured transformed SOBP beam profile through the wedge module rendered as flat. Even though the flat-panel detector exhibited quenching effect at the Bragg peak region, the proton range can still be accurately measured. The device can fulfill the requirements of the daily QA tests recommended by the AAPM TG224 Report.

Current delivery limitations of proton PBS for FLASH

PurposeProton Pencil Beam Scanning (PBS) is an attractive solution to realize the advantageous normal tissue sparing elucidated from FLASH high dose rates. The mechanics of PBS spot delivery will impose limitations on the effective field dose rate for PBS. MethodsThis study incorporates measurements from clinical and FLASH research beams on uniform single energy and the spread-out Bragg Peak PBS fields to extrapolate the PBS dose rate to high cyclotron beam currents 350, 500, and 800 nA. The impact of the effective field dose rate from cyclotron current, spot spacing, slew time and field size were studied. ResultsWhen scanning magnet slew time and energy switching time are not considered, single energy effective field FLASH dose rate (≥40 Gy/s) can only be achieved with less than 4 × 4 cm2 fields when the cyclotron output current is above 500 nA. Slew time and energy switching time remain the limiting factors for achieving high effective dose rate of the field. The dose rate-time structures were obtained. The amount of the total dose delivered at the FLASH dose rate in single energy layer and volumetric field was also studied. ConclusionIt is demonstrated that while it is difficult to achieve FLASH dose rate for a large field or in a volume, local FLASH delivery to certain percentage of the total dose is possible. With further understanding of the FLASH radiobiological mechanism, this study could provide guidance to adapt current clinical multi-field proton PBS delivery practice for FLASH proton radiotherapy.

Producing a Beam Model of the Varian ProBeam Proton Therapy System using TOPAS Monte Carlo Toolkit.

A Geant4-based TOPAS Monte Carlo toolkit was utilized to model a Varian ProBeam proton therapy system, with the aim of providing an independent computational platform for validating advanced dosimetric methods. The model was tested for accuracy of dose and linear energy transfer (LET) prediction relative to the commissioning data, which included integral depth dose (IDD) in water and spot profiles in air measured at varying depths (for energies of 70 to 240MeV in increments of 10MeV, and 242MeV), and absolute dose calibration. Emittance was defined based on depth-dependent spot profiles and Courant-Snyder's particle transport theory, which provided spot size and angular divergence along the inline and crossline plane. Energy spectra were defined as Gaussian distributions that best matched the range and maximum dose of the IDD. The validity of the model was assessed based on measurements of range, dose to peak difference, mean point to point difference, spot sizes at different depths, and spread-out Bragg peak (SOBP) IDD and was compared to the current treatment planning software (TPS). Simulated and commissioned spot sizes agreed within 2.5%. The single spot IDD range, maximum dose, and mean point to point difference of each commissioned energy agreed with the simulated profiles generally within 0.07mm, 0.4%, and 0.6%, respectively. A simulated SOBP plan agreed with the measured dose within 2% for the plateau region. The protons/MU and absolute dose agreed with the current TPS to within 1.6% and exhibited the greatest discrepancy at higher energies. The TOPAS model agreed well with the commissioning data and included inline and crossline asymmetry of the beam profiles. The discrepancy between the measured and TOPAS-simulated SOBP plan may be due to beam modeling simplifications of the current TPS and the nuclear halo effect. The model can compute LET, and motivates future studies in understanding equivalent dose prediction in treatment planning, and investigating scintillation quenching.

Commissioning and validation of TOPAS beam model for IBA Proteus-ONE at UFHPTI

Proteus-ONE (P-ONE) is a novel compact single-room system developed by Ion Beam Application (IBA, Belgium) for proton therapy. The objective of this research was to commission and validate Monte Carlo (MC) beam model for P-ONE using the TOol of PArticle Simulation (TOPAS) Monte Carlo software package. Thirty-three energies were determined within P-ONE energy range (70–227 MeV) to measure integral depth dose (IDD), absolute dose and in-air lateral profiles. The beam model was established by matching TOPAS simulation with measurement for each energy. To validate the accuracy of obtained TOPAS beam model, we compared TOPAS simulation with measurement under various scenarios, including different spread-out Bragg peaks, lateral dose curves and gamma passing rates (GPRs) for 3 × 3x3 cm3, 5 × 5x5 cm3, and 7 × 7x7 cm3 uniform target in a water phantom. Good agreement was observed and GPRs reached 100% among all measurement planes with 3%/3 mm criteria and above 95% with 2%/2 mm criteria. Three patient cases including head and neck, breast and prostate were used for gamma analysis and at least GPRs of 99.8% and 95.4% were reached among all measurement planes with the criteria of 3%/3 mm and 2%/2 m, respectively. The results indicated the accuracy and reliability of the obtained TOPAS beam model which has the potential to serve clinical or research purposes.

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model.

The importance of hadron therapy in the cancer management is growing. We aimed to refine the biological effect detection using a vertebrate model. Embryos at 24 and 72 h postfertilization were irradiated at the entrance plateau and the mid spread-out Bragg peak of a 150 MeV proton beam and with reference photons. Radiation-induced DNA double-strand breaks (DSB) and histopathological changes of the eye, muscles and brain were evaluated; deterioration of specific organs (eye, yolk sac, body) was measured. More and longer-lasting DSBs occurred in eye and muscle cells due to proton versus photon beams, albeit in different numbers. Edema, necrosis and tissue disorganization, (especially in the eye) were observed. Dose-dependent morphological deteriorations were detected at ≥10 Gy dose levels, with relative biological effectiveness between 0.99±0.07 (length) and 1.12±0.19 (eye). Quantitative assessment of radiation induced changes in zebrafish embryos proved to be beneficial for the radiobiological characterization of proton beams.

Scanning Proton FLASH Irradiation Using a Synchrotron Accelerator: Effects on Cultured Cells and Differences by Irradiation Positions

An ultra-high dose rate radiation (FLASH) is now attracting great attention. Although FLASH radiation with a cyclotron-type proton therapy machine has been reported, production of the ultra-high dose rate using other machines has scarcely been reported. In this study, we established a FLASH radiation system using a synchrotron proton beam accelerator and compared the effects of FLASH and conventional dose-rate radiation on cultured cells. Both types of radiation were delivered at the 1-cm spread-out Bragg peak (SOBP) and plateau region before SOBP. Protons were accelerated by adjusting the application pattern of high-frequency power. Other incident conditions for passive irradiation were also applied to increase proton accumulation to approximately twice the normal scanning conditions. Ultra-high dose rates were achieved by applying a high-frequency power dozens of times higher than usual to extract all protons within approximately 50 ms, thereby monitoring with a Faraday cup immediately after synchrotron extraction and adjusting the waveform. The dose and dose rates were measured using a float glass, gafchromic film, and plane parallel ionization chamber. Four cultured tumor cell lines and two normal cell lines were used. FLASH radiation at 6 and 10 Gy (200 Gy/s, 1 shot) and conventional radiation at 6 and 10 Gy (3 Gy/s) were delivered to the SOBP and plateau region before SOBP. After radiation, appropriate amounts of reagents to stain caspase-3/7 were added, and differences in cell growth rates and cell cycle were examined using live-cell fluorescence time-lapse imaging. The cell confluence ratio and apoptotic change were also quantified. V79 spheroids were subjected to FLASH (300 Gy/s, 10 and 18 Gy, 1 shot) and conventional radiation (3 Gy/s, 10 and 18 Gy) at SOBP. Subsequently, they were disaggregated to single cells and assayed for cell survival by colony assay. A 1-cm SOBP was formed by a mini-ledge filter was prepared with a high-definition 3D printer. FLASH radiation could be achieved at 40-800 Gy/s. In vitro, similar cell-killing effects were observed for FLASH and conventional radiation in the cancer cells, with cell-cycle delay. Significant apoptotic effects and G2 arrest during the cell cycle were observed for FLASH peak irradiation, probably due to the higher LET at the Bragg peak. Decreased proliferation and cell-killing effects were also observed in the normal cells for FLASH, but the apoptotic effect was not different between FLASH and conventional irradiation. Stronger cell-killing effects were observed with the V79 spheroids for FLASH peak than conventional peak irradiation. Scanning proton FLASH radiation with a synchrotron accelerator was established for biological studies. FLASH seemed to be equally effective for cancer and normal cells in vitro. The effects were higher with FLASH peak irradiation owing to the high LET at the Bragg peak, which is a characteristic of synchrotron accelerators.

Beam Characteristics of the First Clinical 360°-rotational Compact Scanning Pencil Beam Proton Treatment System and Comparisons against a Multi-Room System

This paper is to present the dosimetric characteristics of the first clinical CBCT guided 360˚-rotational compact/single-room scanning pencil beam proton treatment system (SRPT) and comparisons against a recent beam data from a multi-room proton therapy system (MRPT) by the same vendor. The proton beam commissioning was conducted on the first clinical, newly-designed compact ProBeam 360˚ for its scanning pencil beams for protons ranging from 70MeV to 220MeV. The integrated depth dose curves (IDDs) were acquired in water with AP monogenic proton beams using a PTW Bragg peak chamber. The dose output factors, measured by a Marcus chamber at 15 mm transmission beam portion using single layer 10x10 cm2 proton plans, were then incorporated to the iDD's along with a factor of 1.1 for RBE offset. The beam spot sigma sizes were then derived from single Gaussian fitting for the in-air measured spot profiles. After beam modeling and validation for a treatment planning system, the proton dosimetric characteristics were compared against the recent data of MRPT. In contract to MRPT data, the Bragg peaks of SRPT have shown moderately extended proton beam range straggling in the peak region accompanied by a marginally elevated proximal transmission beam portion. This phenomenon displayed more noticeably in the mid-ranged or even high energies. Consequently, IDDs of SRPT showed about 0.41 to 0.94 mm broader Bragg peak widths (Rb80 - Ra80) in energies of 140 MeV or greater, peaked at 180 MeV. About 0.65-0.79 mm slightly extended distal falloffs (Rb20-80) were noticeable for energies between 140 MeV and 170 MeV, consistent with the findings of minimally raised energy sigma in AcurosPT Monte Carlo model. An independent check for the dose and energy accuracy of a spread-out Bragg peak plan on a simple phantom by the IROC showed 1.00 accuracy with 1.00 ±5% allowance. Additional comprehensive end-to-end independent check using a more realistic prostate phantom offered by IROC was reported a 96% accuracy and the passing score at a set passing criterion of 85%. The result over 108 patient specific individual field QAs with Octavius 1500 2D ionization chamber array showed 100% passing rate using a Gamma index of 3%/3mm or tighter from fields with or without range shifters. The high QA passing rates suggest a high confidence on the accuracy and quality of the commissioning for the newly designed SRPT. The commissioning results of the new-designed SRPT showed slightly widened proton Bragg peaks, elevated beam transition region and extended peak distal falloffs, particularly in mid-high energies, suggest minimally broader spectra for selected proton energies in comparing against MRPT data. This did not show a meaningful impact on the quality and accuracy of proton therapy program, indicated by high scores from independent dosimetry end-to-end checks and over 108 patient’s specific beam QA’s.

2D range modulator for high-precision water calorimetry in scanned carbon-ion beams

Ionization chamber-based dosimetry for carbon-ion beams still shows a significantly higher standard uncertainty than high-energy photon dosimetry. This is mainly caused by the high standard uncertainty of the correction factor for beam quality . Due to a lack of experimental data, the given values for are based on theoretical calculations. To reduce this standard uncertainty, factors for different irradiation conditions and ionization chambers (ICs) can be determined experimentally by means of water calorimetry. To perform such measurements in a spread-out Bragg peak (SOBP) for a scanned carbon-ion beam, we describe the process of creating an almost cubic dose distribution of about 6 × 6 × 6 cm3 using a 2D range modulator. The aim is to achieve a field homogeneity with a standard deviation of measured dose values in the middle of the SOBP (over a lateral range and a depth of about 4 cm) below 2% within a scanning time of under 100 s, applying a dose larger than 1 Gy. This paper describes the optimization and characterization of the dose distribution in detail.

Spectroscopic analysis of irradiated radiochromic EBT-XD films in proton and photon beams

The response of GafchromicTM EBT-XD films to proton irradiation using a Mevion S250TM proton therapy system is studied in this work. Film samples from different batches were irradiated with doses from 0.25 Gy to 20 Gy using a Mevion S250 spread-out Bragg peak (SOBP) clinical proton beam. Using a fiber-coupled optical spectrometer, transmission spectra of the films were acquired over 400–800 nm range (with 2.5 nm resolution). The optical density (OD) of the films was also measured with a flatbed scanner. The characteristics of the film were investigated for dependencies on dose, inter-batch, energy, linear energy transfer (LET), and radiation type. Post-irradiation temporal growth of the OD of the films was also investigated. The net absorbance spectra of EBT-XD films exhibited two absorption peaks located at 636 nm and 585 nm. The measurement of percentage depth dose with the films showed ∼1%–5% and 7%–8% under-estimation on the dose in mid-SOBP and distal SOBP regions, respectively, compared to ionization chamber measurement. No significant energy dependence was noted in the OD of the films when irradiated at the same dose using different proton energies. Approximately 4%–10% drop in spectral response was seen for the proton-irradiated films relative to the films irradiated in photon beams. Temporal growth of the optical density showed a different developing slope between photon and proton irradiation in the first 12 h, but both reached a stable response 24 h after irradiation.

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter.

The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62MeV ocular therapy proton beams. A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100µm×100µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( ), dose mean lineal energy ( ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1keV/μm. The and values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

Simulation of dose distribution and secondary particle production in proton therapy of brain tumor.

The aim of this study is simulation of the proton depth-dose distribution and dose evaluation of secondary particles in proton therapy of brain tumor using the GEANT4 and FLUKA Monte Carlo codes. Proton therapy is a treatment method for variety of tumors such as brain tumor. The most important feature of high energy proton beams is the energy deposition as a Bragg curve and the possibility of creating the spread out Bragg peak (SOBP) for full coverage of the tumor. A spherical tumor with the radius of 1 cm in the brain is considered. A SNYDER head phantom has been irradiated with 30-130 MeV proton beam energy. A PMMA modulator wheel is used for covering the tumor. The simulations are performed using the GEANT4 and FLUKA codes. Using a modulator wheel, the Spread Out Bragg Peak longitudinally and laterally covers the tumor. Flux and absorbed dose of secondary particles produced by nuclear interactions of protons with elements in the head are considerably small compared to protons. Using 76.85 MeV proton beam and a modulator wheel, the tumor can be treated accurately in the 3-D, so that the distribution of proton dose in the surrounding tissues is very low. The results show that more than 99% of the total dose of secondary particles and protons is absorbed in the tumor.

A radiobiological study of carbon ions of different linear energy transfer in resistant human malignant cell lines

Purpose Analysis of elimination of four human radioresistant malignant cell lines to mono-energetic and non mono-energetic incoming carbon ion beams, characterized by different linear energy transfer (LET) qualities is performed. Comparisons with protons from the middle of the therapeutic spread out Bragg peak (SOBP) and reference γ-rays are also included. Materials and methods HTB140 cells were irradiated at five positions, with different LET, along the 62 MeV carbon pristine Bragg peak. To provide reliable reproducibility of irradiations at INFN-LNS, as the carbon Bragg peak is very narrow, precise positioning of samples for desired LET value is complicated. The peak was slightly widened using two ripple filters. After defining irradiation position and LET at the peak itself where cell killing is almost the highest, irradiation position with the same LET value was found within somewhat broadened peak. HTB140, MCF-7, HTB177 and CRL5876 cells were irradiated at the two described positions. Additionally, irradiations in the middle of 62 MeV proton SOBP and reference γ-rays were performed. Doses ranged from 0.5 to 16 Gy. Cell survival and corresponding radiobiological parameters were assessed seven days after irradiations. Results When moving irradiation position along the carbon Bragg curve, LET rises from 85 to 747 keV/µm, while surviving fraction at 2 Gy (SF2) for HTB140 cells, falls from 0.72 to 0.57 further rising to 0.73 on the distal fall-off part of the curve. Improved cell radiosensitivity is seen for the doses below 4 Gy. Relative biological effectiveness (RBE) increases from 4.56 to 7.69 and drops to 4.23. Almost the highest cell killing LET, being ∼200 keV/µm, is used to irradiate HTB140, MCF-7, HTB177 and CRL5876 cells within the pristine and slightly broadened Bragg peak. After irradiations with protons of the mid SOBP, carbon ions of the pristine and slightly widened Bragg peak RBE ranges for HTB140 cells from 2.08, 4.81 to 7.06, for MCF-7 from 1.70, 3.28 to 4.17, for HTB177 from 1.98, 4.18 to 5.08 and for CRL5876 from 1.33, 2.57 to 3.51. Conclusions Significant elimination of HTB140 cells is observed along the carbon Bragg curve. The highest one is achieved by LET that is at the level of already reported. For the same LET, mono-energetic carbon ions provide higher cell elimination than the non mono-energetic. For all cell lines, both carbon ion beams, more the monoenergetic one, express stronger killing rate than protons and especially γ-rays.

Safety Evaluation of a Long-Lived Tumour-Specific Gadolinium (Gd)-Based Imaging Agent in Proton Therapy

We assessed the dosimetric safety of a potential diapeutic Gadolinium-based contrast agent for diagnostic MR imaging and MR-guided radiotherapy by calculating depth-dependent reactions rates in a spread-out Bragg peak (SOBP) in water. Energy-dependent cross-sections for inelastic proton reactions on Gadolinium were folded with proton energy spectra at depth. Particle transport, dose, and phase space scoring was performed using Geant4-based TOPAS Monte Carlo software. The isotopic Terbium yield at depth was calculated to be between 103 to 105 atoms/mmolnatGd per Gray SOBP dose in a 2.4 cm3 volume. At currently achievable Gadolinium concentrations of 0.2 μmol/cm3 this yields approximately 26 atoms/(cm3 GySOBP), corresponding to less than 1 Bq activity. Additional dose from evaporation neutrons and subsequent capture gammas is on the order of 1 μSv/GySOBP. Thus, use of this long-lived contrast agent is dosimetrically safe at current concentrations and induced radioactivity is negligible.