L. Perles

An MCNPX Monte Carlo model of a discrete spot scanning proton beam therapy nozzle

PURPOSE The purposes of this study were to validate a discrete spot scanning proton beam nozzle using the Monte Carlo (MC) code MCNPX and use the MC validated model to investigate the effects of a low-dose envelope, which surrounds the beams central axis, on measurements of integral depth dose (IDD) profiles. METHODS An accurate model of the discrete spot scanning beam nozzle from The University of Texas M. D. Anderson Cancer Center (Houston, Texas) was developed on the basis of blueprints provided by the manufacturer of the nozzle. The authors performed simulations of single proton pencil beams of various energies using the standard multiple Coulomb scattering (MCS) algorithm within the MCNPX source code and a new MCS algorithm, which was implemented in the MCNPX source code. The MC models were validated by comparing calculated in-air and in-water lateral profiles and percentage depth dose profiles for single pencil beams with their corresponding measured values. The models were then further tested by comparing the calculated and measured three-dimensional (3-D) dose distributions. Finally, an IDD profile was calculated with different scoring radii to determine the limitations on the use of commercially available plane-parallel ionization chambers to measure IDD. RESULTS The distance to agreement, defined as the distance between the nearest positions of two equivalent distributions with the same value of dose, between measured and simulated ranges was within 0.13 cm for both MCS algorithms. For low and intermediate pencil beam energies, the MC simulations using the standard MCS algorithm were in better agreement with measurements. Conversely, the new MCS algorithm produced better results for high-energy single pencil beams. The IDD profile calculated with cylindrical tallies with an area equivalent to the area of the largest commercially available ionization chamber showed up to 7.8% underestimation of the integral dose in certain depths of the IDD profile. CONCLUSIONS The authors conclude that a combination of MCS algorithms is required to accurately reproduce experimental data of single pencil beams and 3-D dose distributions for the scanning beam nozzle. In addition, the MC simulations showed that because of the low-dose envelope, ionization chambers with radii as large as 4.08 cm are insufficient to accurately measure IDD profiles for a 221.8 MeV pencil beam in the scanning beam nozzle.

Adjustment of the lateral and longitudinal size of scanned proton beam spots using a pre-absorber to optimize penumbrae and delivery efficiency.

In scanned-beam proton therapy, the beam spot properties, such as the lateral and longitudinal size and the minimum achievable range, are influenced by beam optics, scattering media and drift spaces in the treatment unit. Currently available spot scanning systems offer few options for adjusting these properties. We investigated a method for adjusting the lateral and longitudinal spot size that utilizes downstream plastic pre-absorbers located near a water phantom. The spot size adjustment was characterized using Monte Carlo simulations of a modified commercial scanned-beam treatment head. Our results revealed that the pre-absorbers can be used to reduce the lateral full width at half maximum (FWHM) of dose spots in water by up to 14 mm, and to increase the longitudinal extent from about 1 mm to 5 mm at residual ranges of 4 cm and less. A large factor in manipulating the lateral spot sizes is the drift space between the pre-absorber and the water phantom. Increasing the drift space from 0 cm to 15 cm leads to an increase in the lateral FWHM from 2.15 cm to 2.87 cm, at a water-equivalent depth of 1 cm. These findings suggest that this spot adjustment method may improve the quality of spot-scanned proton treatments.

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.

SU-E-T-584: Commissioning of the MC2 Monte Carlo Dose Computation Engine

PURPOSE An automated system, MC2, was developed to convert DICOM proton therapy treatment plans into a sequence MCNPX input files, and submit these to a computing cluster. MC2 converts the results into DICOM format, and any treatment planning system can import the data for comparison vs. conventional dose predictions. This work describes the data and the efforts made to validate the MC2 system against measured dose profiles and how the system was calibrated to predict the correct number of monitor units (MUs) to deliver the prescribed dose. METHODS A set of simulated lateral and longitudinal profiles was compared to data measured for commissioning purposes and during annual quality assurance efforts. Acceptance criteria were relative dose differences smaller than 3% and differences in range (in water) of less than 2 mm. For two out of three double scattering beam lines validation results were already published. Spot checks were performed to assure proper performance. For the small snout, all available measurements were used for validation vs. simulated data. To calibrate the dose per MU, the energy deposition per source proton at the center of the spread out Bragg peaks (SOBPs) was recorded for a set of SOBPs from each option. Subsequently these were then scaled to the results of dose per MU determination based on published methods. The simulations of the doses in the magnetically scanned beam line were also validated vs. measured longitudinal and lateral profiles. The source parameters were fine tuned to achieve maximum agreement with measured data. The dosimetric calibration was performed by scoring energy deposition per proton, and scaling the results to a standard dose measurement of a 10 x 10 x 10 cm3 volume irradiation using 100 MU. RESULTS All simulated data passed the acceptance criteria. CONCLUSION MC2 is fully validated and ready for clinical application.

TH‐F‐105‐05: Comparison of Results for RBE‐Weighted Dose From Two RBE Models for Proton Therapy Treatment Plans

PURPOSE To evaluate the differences between relative biological effectiveness (RBE)-weighted doses calculated with either the linear quadratic (LQ) or repair-misrepair-fixation (RMF) RBE model for intensity modulated proton therapy (IMPT) treatment plans. METHODS The commercial treatment planning system (TPS) used at MD Anderson Cancer Center (MDACC) does not provide the LET information necessary in order to utilize variable RBE models to calculate RBE-weighted dose for treatment plans. To obtain this information the Monte Carlo code MCNPX was used to recalculate IMPT treatment plans for patients with central nervous system (CNS) disease taken from the TPS and record the track-averaged LET in each voxel of the dose distribution. The dose-averaged LET was approximated from the track-averaged LET by use of an appropriate scaling factor. The Monte Carlo Damage Simulation (MCDS) software was used to parameterize the number of double-strand breaks generated in cells by protons according to their stopping power. This information, along with relevant biological coefficients, was then used to generate RBE-weighted dose distributions according to the LQ and RMF RBE models. Plan evaluation metrics, such as a conformality index and heterogeneity index, were used for plan comparison. RESULTS The LQ RBE model produces higher RBE-weighted doses, particularly in the target volume, compared to the RMF model. Doses predicted by the RMF model in nearby organs at risk can at times be several Gray lower than those predicted by the LQ model. Both models predict equivalently heterogeneous target dose distributions, while the RMF model predicts more conformal target dose. CONCLUSION Calculation of proton treatment plan dose incorporating either the LQ or RMF models of variable RBE produces observable differences in the resultant dose distributions. Further investigation, including utilization of different biological coefficients, is required to determine the implications for all of the associated normal tissues. UTMDACC Sister Institution Network Fund Grant (SINF MDACC-DKFZ).

SU‐E‐T‐297: Modeling the Cell Inactivation Process for High LET Particles by Using the Law of Mass Action

PURPOSE To develop a method to model the cell inactivation caused by photons or light ions irradiation that accurately describes the survival curves for various linear energy transfer (LET) as well as high dose survival curves. METHODS We adapted the law of mass action widely used in physical chemistry to model the cell inactivation process through a differential equation. Its solution depends on two parameters, D0 and p. D0 is positive and represents the dose that causes a survival of 37%; p is a dimensionless parameter equal or greater to 1. We evaluated our model using data available in the literature for four human cancer cell lines (DU-145, CP3, U1690 and H460) exposed to 137 Cs and doses up to 20 Gy; and to V79 cells exposed to 240 kVp x-rays and to light ions (protons, deuterons and 3 He) of various LET ranging from 10 to 105 keV um-1 . RESULTS Our model was capable to fit survival curves for the human cancer cell lines up to 20 Gy as good as the linear quadratic model. D0 was determined with uncertainty better than 4% and ranged from 2.7 to 3.8 Gy; p was determined with uncertainty better than 6% and ranged from 1.3 to 1.7. For the V79 data, the parameters Do and p exhibited a well-defined exponential dependence on the LET. Also, the p was found to approach 1 asymptotically, as predicted by the theory. The RBE as a function of LET was also accurately determined. CONCLUSION The adapted law of mass action for the radiobiology provides an accurate model to study the cell survival curves under various conditions. Furthermore, it sets useful limits to the parameters that could be verified experimentally. NCI grant P01CA021239.

TU‐G‐108‐08: Variable RBE and Incidence of Radiation Pneumonitis in Lung Patients Treated with Proton Therapy

PURPOSE To determine the correlation between the Relative Biological Effectiveness (RBE)-weighted dose and radiation pneumonitis (RP) incidence in cancer patients treated with proton therapy. METHODS The Monte Carlo proton dose calculation system MC2 based on MCNPX was used to recalculate treatment plans taken from the clinical treatment planning system (TPS) and compute the dose-averaged LET in each voxel of the CT based patient model. The linear scaling model (LSM) for proton RBE was used with biological coefficients for RP to compute the variable RBE-weighted dose distributions. These were compared with the constant RBE-weighted doses computed by the TPS and currently used in our clinical practice. A restaging FDG PET/CT was registered to the treatment planning CT and the standard uptake values (SUV) were used as a measure of radiation dose response. RESULTS The variable RBE model results in higher biological dose at the distal ends of proton beams and the corresponding lung volumes receiving elevated doses can be significant if the beam is terminating inside the low density lung tissue. Preliminary results for the first two patients in the study show that the regions of elevated variable RBE-weighted doses inside the lung are well correlated to the high SUV values in the restaging PET. Both patients were diagnosed with grade 3 RP after completing the treatment. CONCLUSION The preliminary results indicate that variable RBE-weighted doses may provide additional insight into toxicity risk for patients treated with proton radiotherapy. The complete study will include the analysis of many more patients diagnosed with grade 3 RP or higher, treated with protons in our institution. NCI grant P01CA021239.

TH‐F‐105‐03: Experimental Design and Preliminary Results for High‐Resolution and High‐Throughput In‐Vitro Measurements of Proton RBE

PURPOSE To design, develop and test a novel system for rapidly acquiring large amounts of in-vitro RBE data for protons as a function of LET, dose per fraction, dose rate, end point, and oxygenation for a wide range of cell lines. METHODS Using the Geant4 Monte Carlo toolkit, we designed a specialized range compensator to simultaneously expose cells plated in 96 wells (12 columns by 8 rows) to different doses and variable LETs from selected portions of pristine proton beams from the entrance to points just beyond the Bragg peak. The use of 96-well plates can facilitate future high-throughput and high-resolution measurements. To minimize the spread of LET, we utilized monoenergetic uniformly scanned proton beams. Using a sequence of entrance doses and variable LETs, an RBE matrix related to different pairs of doses and LETs can be acquired in a relatively small number of exposures. In this study, we utilized the standard clonogenic assay for lung-cancer cell lines grown in 96-well plates. The compensator is mounted in the scanning beam snout with the beam directed toward the ceiling. In each exposure, one 96-well plate was positioned downstream for irradiation. RESULTS Experimental data for lung cancer cells exposed to 79.7 MeV protons showed a significant increase in cell kill as a function of LET at locations close to the distal edge of the Bragg peak. For LET values of 8.34, 11.6, 13.5 and 14.6 keV/μm, the surviving fractions were found to be 0.24, 0.18, 0.088 and 0.031 at 4 Gy and 0.11, 0.074, 0.024 and 0.0035 at 6 Gy. CONCLUSION The experimental design developed is a viable approach to rapidly acquire large amounts of accurate in-vitro RBE data. We plan to further improve the design to achieve higher accuracy and throughput, thereby facilitating the irradiation of multiple cell types. NCI grant P01CA021239.

TH‐E‐BRB‐04: Dose Response of EBT2 Film Modeled as a Bimolecular Reaction

Purpose: This study investigated if the dose‐response of EBT2 film can be modeled as a bimolecular reaction of the monomers that composes the active layer of the EBT2 film. The LET dependence of EBT2 films was explored using the models developed in this study. Methods: To build a dose‐response curve a set of films was exposed to pristine proton beams of 161.61 MeV, with doses ranging from 0.93 Gy to 14.82 Gy at a depth of 2 cm in water. The same procedure was applied to a film using a lower energy beam, 85.55 MeV. Because the chemical models predict different values for the maximum optical density of the film, another set of films was exposed to a higher dose, about 200 Gy, to determine which chemical model would better predict the film parameters. Fluence‐averaged LET curves were computed by calculating the ratio of the dose and fluence in water. Proton energy spectra were also computed at selected depths for both energies. Results: The unimolecular and the bimolecular models were able to accurately fit the experimental data, with both having R2 = 0.9996. The maximum optical density values found were 0.901 +/− 0.050 by the unimolecular model and 1.276 +/− 0.077 by the bimolecular model. Exposing a set of EBT2 films to 200 Gy yielded a measured optical density of 1.360 +/− 0.070, which indicated larger systematic uncertainties in the unimolecular model compared to the bimolecular model. Conclusions: Although both the unimolecular and the bimolecular models fit the experimental data with similar accuracy, only the bimolecular model could predict the maximum optical density of the EBT2 film with acceptable accuracy. We also observed that the energy spectra at the measurement depths play a role in the LET response of the EBT2 films when described as a bimolecular reaction. 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.

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.