The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

LET dependence of the response of EBT2 films in proton dosimetry modeled as a bimolecular chemical reaction.

The dose response for films exposed to clinical x-ray beams is not linear and a calibration curve based on absorbed dose can be used to account for this effect. However for proton dosimetry the dose response of films exhibits an additional dependence because of the variation of the linear energy transfer (LET) as the protons penetrate matter. In the present study, we hypothesized that the dose response for EBT2 films can be mathematically described as a bimolecular chemical reaction. Furthermore, we have shown that the LET effect can be incorporated in the dose-response curve. A set of EBT2 films was exposed to pristine 161.6 MeV proton beams. The films were exposed to doses ranging from 0.93 to 14.82 Gy at a depth of 2 cm in water. The procedure was repeated with one film exposed to a lower energy beam (85.6 MeV). We also computed the LET and dose to water in the sensitive layer of the films with a validated Monte Carlo system, taking into account the film construction (polyester, adhesive and sensitive layers). The bimolecular model was able to accurately fit the experimental data with a correlation factor of 0.9998, and the LET correction factor was determined and incorporated into the dose-response function. We also concluded that the film orientation is important when determining the LET correction factor because of the asymmetric construction of the film.

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system.

PURPOSE: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). METHODS: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. RESULTS: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. CONCLUSIONS: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.

Comparison of MCNPX and Geant4 proton energy deposition predictions for clinical use.

Several different Monte Carlo codes are currently being used at proton therapy centers to improve upon dose predictions over standard methods using analytical or semi-empirical dose algorithms. There is a need to better ascertain the differences between proton dose predictions from different available Monte Carlo codes. In this investigation Geant4 and MCNPX, the two most-utilized Monte Carlo codes for proton therapy applications, were used to predict energy deposition distributions in a variety of geometries, comprising simple water phantoms, water phantoms with complex inserts and in a voxelized geometry based on clinical CT data. The Gamma analysis was used to evaluate the differences of the predictions between the codes. The results show that in all the cases the agreement was better than clinical acceptance criteria.

WE-E-BRB-02: Evaluation of Analytical Proton Dose Predictions with a Lung-Like Plastic Phantom.

PURPOSE: Former studies have shown that in homogeneities in the path of therapeutic proton beams can lead to a degradation of the distal edge of the Bragg peak. These studies mostly investigated bone-air interfaces. This study focuses on distal edge degradation caused by finely structured soft tissue - air interfaces, which can be found in lung tissue. METHODS: A randomly filled voxelized lung-like phantom was designed and produced using rapid prototyping methods. The results of transmission measurements on this phantom were used to validate Monte Carlo (MC) calculations, which were then used as gold standard to calculate doses in several lung equivalent geometries (phantoms). The results were compared to the results of analytical dose calculation engines. RESULTS: Transmission measurements showed that the distal falloff width (from 90 % of the peak dose to 10 %) in water increased from 3.32 mm by 117 % to 7.19 mm for an initial proton energy of 140 MeV, and from 5.95 mm to 9.03 mm (52 %) for 200 MeV. The peak dose in the degraded beam was only 70 % (for 140 MeV) and 84 % (for 200 MeV) of the value observed in non-degraded beams. These findings were in contrast to the results obtained with analytical dose computation engines, but are in agreement with MC calculations. CONCLUSIONS: If not predicted correctly, Distal Edge Degradation in lung cancer therapy can lead to severe under-dosage of the target region and unwanted dose in organs at risk distal to the Bragg peak. Therefore clinically used dose calculation algorithms have to be extended to take lateral in homogeneities into account.

SU-E-T-435: Automatic Monte Carlo Dose Calculations of Proton Treatment Plans.

PURPOSE: Providing a user friendly automated Monte Carlo dose computation system for proton treatments using passively scattered and intensity modulated proton therapy plans, developed at the proton therapy facility of the M.D. Anderson Cancer Center. METHODS: In house software was developed to automatically extract patient CT images, as well as the setup geometry and proton beam parameters from DICOM files, to create a Monte Carlo (MCNPX) model simulating the beam line arrangements of the various beams used in any given proton treatment plan. A graphical user interface provides an easy and intuitive workspace. A library of phase space files provides source proton beams with the desired modulation width and range in water. Energy deposition is scored in the voxelized CT volume, converted to dose and compared to results of analytical dose computations. RESULTS: Monte Carlo models of patient specific beam line equipment, such as the brass collimator and the range compensator, as well as avoxelized model of the patient, are automatically created and implemented into the model of the simulated beam. Simulation of proton beams result in energy deposition distributions in a volume of interest defined by the user during program start. CONCLUSIONS: Current efforts focus on production ofthe phase space library and final debugging of the program flow. It is expected that a prototype version of the system will be functional in summer 2012.

SU-E-T-396: Beam Angle Optimization for IMPT Comparing Gantries and Fixed Beam Lines.

PURPOSE: To explore the potential of beam angle optimization (BAO) for IMPT and compare fixed beamlines with gantries. METHODS: For three patients with challenging intracranial lesions, we generate reference IMPT treatment plans applying three manually selected beam orientations and treatment plans applying three optimized beam orientations considering five scenarios: (1) patients are in supine position and the treatment room features (1.a) a horizontal beamline, (1.b) a horizontal, 45°, and vertical beamline, (1.c) a gantry, (2) patients are in supine or seated position and the treatment room features (2.a) a horizontal beamline, or (2.b) a horizontal, 45°, and vertical beamline. We use a genetic algorithm that considers up to 1,400 non-coplanar candidate beams and evaluates 10,000 beam ensembles for one BAO. Beam orientations that may compromise the robustness of treatment plans are excluded before the optimization based on an objective measure of existing tissue heterogeneities. RESULTS: The optimized beam ensembles exhibit certain similarities even though the sets of candidate beams differ significantly for the five scenarios. Compared to manually selected beam orientations, they provide improved OAR sparing and equivalent target coverage. Compared to one another, they yield comparable target conformity (deviations of the conformity number <1%), target homogeneity (standard deviations of the target dose <0.8 Gy), and sparing of OARs (deviations of average mean and maximum doses in OARs +/- 1 Gy). Using a gantry, however, the integral dose can be reduced by 5-15% compared to a horizontal beamline with patients in supine position. For the investigated cases comparable reductions can be achieved by also irradiating in seated position with a horizontal, 45°, and vertical beamline. CONCLUSIONS: BAO has the potential to provide beneficial IMPT treatment plans. Compared to fixed beamlines, gantries yield only modest effects regarding OAR sparing but may enable a significant reduction of integral dose for individual patients.

SU-E-T-474: Monte Carlo Phase Space Production to Model Magnetically Scanned Proton Beams for IMPT.

PURPOSE: Accurate dose predictions in proton beam therapy using magnetically scanned beams are highly dependent on the accurate modeling of the lateral dose profiles. This study was performed to provide proton phase spaces for Monte Carlo simulations, used to accurately simulate doses at distances up to 12 cm from the central axis of the beam. METHODS: Measured lateral dose profiles at various depths in water were compared to Monte Carlo simulations of doses for 90 discreet initial proton energies. Phase spaces were produced using a one dimensional energy distribution, and a combination of several two dimensional spatial and directional distributions. Simulations were performed iteratively using variations in the initial phase space distributions to achieve acceptable agreement between measured and simulated lateral dose profiles, i.e. differences in FWHM < 0.5 mm and dose differences less that 0.1% at distances up to 12.5 cm. RESULTS: 90 phase spaces of proton sources for different initial beam energies were created for use in Monte Carlo simulations of scanned proton beam therapy patient plans. At a depth of 2 cm in water, the simulated and measured FWHM of the lateral dose profiles differed in in-plane direction by an average of 0.05 mm, in cross-plane direction by 0.13 mm. All simulated profiles were within 0.1% of the measured doses at distances between 2cm and 12.5 cm from the central beam axis. CONCLUSIONS: A library of 90 phase space files has been created to accurately simulate magnetically scanned proton beams for IMPT, providing accurate dose distributions up to 12 cm distance from the central beam axis. This project is supported in part by P01CA021239 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

SU-E-T-484: Potential Clinical Impact of Dosimetric Uncertainties in Proton Therapy.

PURPOSE: The analytical algorithms which are used widely for proton treatment planning in the current clinical practice may have significant dosimetric uncertainties in highly heterogeneous regions. The aim of this study is the assessment of the potential clinical impact of these uncertainties. METHODS: A cohort of 8 patients with local (in field) recurrences, originally treated for lung cancer at our institution, was selected for this study. CT scans and treatment plans were used to assemble the input files for the Monte Carlo (MC) code MCNPX. The total energy deposition inside the patient volume was computed with statistical uncertainty of less than 2% and converted to dose-in-water. The results were compared to the dose computed by the clinical treatment planning system (TPS). The area of the recurrence was contoured on the follow-up PET/CT study for each of the patients and registered to the planning CT. RESULTS: While there is acceptable agreement between the TPS and the Monte Carlo dose in homogeneous regions, there are noticeable differences caused by heterogeneities. The regions of largest differences are the points around and beyond the distal edge and points around the lateral penumbra and in several patients the target has received lower then the prescribed dose. The area of the recurrence corelates well with the MC predicted underdosed area of the target. CONCLUSIONS: The uncertanties in analytical dose algorithms used in clinical TPSs may result in suboptimal target coverage increasing the possibility of tumor recurrence. Accurate Monte Carlo simulations can be used to predict and avoid the situations in which the analytical algorithms have high uncertanties providing for more robust treatment planning.

Assessment of the accuracy of an MCNPX-based Monte Carlo simulation model for predicting three-dimensional absorbed dose distributions.

In recent years, the Monte Carlo method has been used in a large number of research studies in radiation therapy. For applications such as treatment planning, it is essential to validate the dosimetric accuracy of the Monte Carlo simulations in heterogeneous media. The AAPM Report no 105 addresses issues concerning clinical implementation of Monte Carlo based treatment planning for photon and electron beams, however for proton-therapy planning, such guidance is not yet available. Here we present the results of our validation of the Monte Carlo model of the double scattering system used at our Proton Therapy Center in Houston. In this study, we compared Monte Carlo simulated depth doses and lateral profiles to measured data for a magnitude of beam parameters. We varied simulated proton energies and widths of the spread-out Bragg peaks, and compared them to measurements obtained during the commissioning phase of the Proton Therapy Center in Houston. Of 191 simulated data sets, 189 agreed with measured data sets to within 3% of the maximum dose difference and within 3 mm of the maximum range or penumbra size difference. The two simulated data sets that did not agree with the measured data sets were in the distal falloff of the measured dose distribution, where large dose gradients potentially produce large differences on the basis of minute changes in the beam steering. Hence, the Monte Carlo models of medium- and large-size double scattering proton-therapy nozzles were valid for proton beams in the 100 MeV-250 MeV interval.

Radiation safety survey on a flattening filter-free medical accelerator.

Dose rates at several locations outside a treatment room were measured for 6 and 18 MV photon beams from a Varian Clinac 21EX accelerator operated with and without a flattening filter. Also, dose rates in the treatment room due to activation were measured at 18 MV. An analysis of the measured data is presented. The results suggest that substantial reduction in doses outside the treatment room and lower activation can be achieved with a flattening-filter free accelerator.

Monte Carlo study of backscatter in a flattening filter free clinical accelerator.

In conventional linear accelerators, the flattening filter provides a uniform lateral dose profile. In intensity modulated radiation therapy applications, however, the flatness of the photon field and hence the presence of a flattening filter, is not necessary. Removing the filter may provide some advantages, such as faster treatments and smaller out-of-field doses to the patients. In clinical accelerators the backscattered radiation dose from the collimators must be taken into account when the dose to the target volume in the patient is being determined. In the case of a conventional machine, this backscatter is known to great precision. In a flattening filter free accelerator, however, the amount of backscatter may be different. In this study we determined the backscatter contribution to the monitor chamber signal in a flattening filter free clinical accelerator (Varian Clinac 21EX) with Monte Carlo simulations. We found that with the exception of very small fields in the 18-MV photon mode, the contribution of backscattered radiation to the monitor signal did not differ from that of conventional machines with a flattening filter. Hence, a flattening filter free clinical accelerator would not necessitate a different backscatter correction.

A flattening filter free photon treatment concept evaluation with Monte Carlo.

In principle, the concept of flat initial radiation-dose distribution across the beam is unnecessary for intensity modulated radiation therapy. Dynamic leaf positioning during irradiation could appropriately adjust the fluence distribution of an unflattened beam that is peaked in the center and deliver the desired uniform or nonuniform dose distribution. Removing the flattening filter could lead to reduced treatment time through higher dose rates and reduced scatter, because there would be substantially less material in the beam; and possibly other dosimetric and clinical advantages. This work aims to evaluate the properties of a flattening filter free clinical accelerator and to investigate its possible advantages in clinical intensity modulated radiation therapy applications by simulating a Varian 2100-based treatment delivery system with Monte Carlo techniques. Several depth-dose curves and lateral dose distribution profiles have been created for various field sizes, with and without the flattening filter. Data computed with this model were used to evaluate the overall quality of such a system in terms of changes in dose rate, photon and electron fluence, and reduction in out-of-field stray dose from the scattered components and were compared to the corresponding data for a standard treatment head with a flattening filter. The results of the simulations of the flattening filter free system show that a substantial increase in dose rate can be achieved, which would reduce the beam on time and decrease the out-of-field dose for patients due to reduced head-leakage dose. Also close to the treatment field edge, a significant improvement in out-of-field dose could be observed for small fields, which can be attributed to the change in the photon spectra, when the flattening filter is removed from the beamline.

Neutron shielding calculations in a proton therapy facility based on Monte Carlo simulations and analytical models: criterion for selecting the method of choice.

Proton therapy facilities are shielded to limit the amount of secondary radiation to which patients, occupational workers and members of the general public are exposed. The most commonly applied shielding design methods for proton therapy facilities comprise semi-empirical and analytical methods to estimate the neutron dose equivalent. This study compares the results of these methods with a detailed simulation of a proton therapy facility by using the Monte Carlo technique. A comparison of neutron dose equivalent values predicted by the various methods reveals the superior accuracy of the Monte Carlo predictions in locations where the calculations converge. However, the reliability of the overall shielding design increases if simulation results, for which solutions have not converged, e.g. owing to too few particle histories, can be excluded, and deterministic models are being used at these locations. Criteria to accept or reject Monte Carlo calculations in such complex structures are not well understood. An optimum rejection criterion would allow all converging solutions of Monte Carlo simulation to be taken into account, and reject all solutions with uncertainties larger than the design safety margins. In this study, the optimum rejection criterion of 10% was found. The mean ratio was 26, 62% of all receptor locations showed a ratio between 0.9 and 10, and 92% were between 1 and 100.

Patient neutron dose equivalent exposures outside of the proton therapy treatment field.

A large fraction of dose to healthy tissue located outside of the treatment field during proton therapy is attributable to neutrons produced in the beam-delivery apparatus. In this work, the neutron dose equivalent (H) per therapeutic proton absorbed dose (D) was estimated for typical treatment conditions as a function of range modulation width, angle with respect to the incident proton beam, and the distance from the isocentre at the Harvard Cyclotron Laboratory's (Cambridge, MA) passively spread treatment field using Monte Carlo simulations. For a beam with 16 cm penetration (depth) and a 5 x 5 cm2 lateral field size at the patient location along the incident beam direction at 100 cm from the isocentre, the predicted H/D values are 0.35 and 0.60 mSv Gy(-1) from the simulations and measurements, respectively. At all locations, the predicted H/D values are within a factor of 2 and 3 of the measured result for no modulation and 8.2 cm of modulation, respectively.

Neutron radiation area monitoring system for proton therapy facilities.

A neutron radiation area monitoring system has been developed for proton accelerator facilities dedicated to cancer therapy. The system comprises commercial measurement equipment, computer hardware and a suite of software applications that were developed specifically for use in a medical accelerator environment. The system is designed to record and display the neutron dose-equivalent readings from 16 to 24 locations (depending on the size of the proton therapy centre) throughout the facility. Additional software applications provide for convenient data analysis, plotting, radiation protection reporting, and system maintenance and administration tasks. The system performs with a mean time between failures of >6 months. Required data storage capabilities and application execution times are met with inexpensive off-the-shelf computer hardware.

Therapeutic step and shoot proton beam spot-scanning with a multi-leaf collimator: a Monte Carlo study.

In step and shoot spot-scanning, a small-diameter proton beam is magnetically swept and varied in energy in order to cover the tumour. Initial estimates of the beam size indicate that additional collimating hardware will be needed for lower energy proton beams in order to achieve a clinically acceptable lateral dose falloff at the edge of the proton beam. In this report, we present dosimetric data from Monte Carlo simulations with a model of a simple multileaf collimator which indicate that such a device may be used to improve the lateral dose falloff. The dosimetric quantities relevant to the clinical usefulness of the device are studied, including lateral penumbra, leaf transmission and scalloping effect. Multileaf collimation is compared with a differential spot-weighting technique of sharpening the lateral dose falloff.

Design tools for proton therapy nozzles based on the double-scattering foil technique.

Proton therapy has been increasing over the past several years, with several new treatment facilities being built in Europe, Japan and the United States. In this work, analytical and Monte Carlo tools were combined to model the passively scattered neurosurgery treatment beamline of the Harvard Cyclotron Laboratory (Cambridge, MA). The predicted three-dimensional dose distributions agree with actual measurements to within 0.1 mm for all quantities considered in central-axis depth-dose curve and to within 2.1 mm for all quantities considered in the absorbed dose cross-field profile. The predicted neutron dose equivalent per therapeutic absorbed dose, H/D, was calculated at various locations representing clinically significant anatomical sites. Under typical treatment conditions, the average ratio of predicted-to-measured H/D is 1.8 in the gonadal region (50 cm from isocentre) and 3.4 in the thyroid region (21 cm from isocentre). The global ratio of predicted-to-measured H/D is 2.6.

Imaging of microscopic features of charged particle tracks in a low-pressure gas.

An imaging system for measuring the spatial distribution of charged particle tracks in a low-pressure gas is presented. The method is based on an optically read out time projection chamber. Results of experiments with fast heavy ions are shown.