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Title: SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

Abstract

Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receivingmore » radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam conforming technique.« less

Authors:
 [1];  [2]; ;  [1];  [1];  [2];  [1];  [2];  [3];  [1];  [4];  [5]
  1. OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany)
  2. (Germany)
  3. Massachusetts General Hospital, Boston, MA (United States)
  4. (DKTK), Dresden (Germany)
  5. (DKFZ), Heidelberg (Germany)
Publication Date:
OSTI Identifier:
22649237
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ANIMAL TISSUES; COMPUTER CODES; COMPUTERIZED TOMOGRAPHY; IN VIVO; LUNGS; MICE; MONTE CARLO METHOD; PLANT TISSUES; PROTON BEAMS; RADIATION DOSES; RADIOTHERAPY; RBE; SIMULATION

Citation Formats

Oesten, H, Massachusetts General Hospital, Boston, MA, Loeck, S, Wohlfahrt, P, Helmbrecht, S, Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf, Tillner, F, Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Schuemann, J, Luehr, A, German Cancer Consortium, and German Cancer Research Center. SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method. United States: N. p., 2016. Web. doi:10.1118/1.4956868.
Oesten, H, Massachusetts General Hospital, Boston, MA, Loeck, S, Wohlfahrt, P, Helmbrecht, S, Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf, Tillner, F, Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Schuemann, J, Luehr, A, German Cancer Consortium, & German Cancer Research Center. SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method. United States. doi:10.1118/1.4956868.
Oesten, H, Massachusetts General Hospital, Boston, MA, Loeck, S, Wohlfahrt, P, Helmbrecht, S, Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf, Tillner, F, Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Schuemann, J, Luehr, A, German Cancer Consortium, and German Cancer Research Center. 2016. "SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method". United States. doi:10.1118/1.4956868.
@article{osti_22649237,
title = {SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method},
author = {Oesten, H and Massachusetts General Hospital, Boston, MA and Loeck, S and Wohlfahrt, P and Helmbrecht, S and Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf and Tillner, F and Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden and Schuemann, J and Luehr, A and German Cancer Consortium and German Cancer Research Center},
abstractNote = {Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam conforming technique.},
doi = {10.1118/1.4956868},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: One of the more critical initiating events for reproductive cell death is the creation of a DNA double strand break (DSB). In this study, we present a computationally efficient way to determine spatial variations in the relative biological effectiveness (RBE) of proton therapy beams within the FLUKA Monte Carlo (MC) code. Methods: We used the independently tested Monte Carlo Damage Simulation (MCDS) developed by Stewart and colleagues (Radiat. Res. 176, 587–602 2011) to estimate the RBE for DSB induction of monoenergetic protons, tritium, deuterium, hellium-3, hellium-4 ions and delta-electrons. The dose-weighted (RBE) coefficients were incorporated into FLUKA to determinemore » the equivalent {sup 6}°60Co γ-ray dose for representative proton beams incident on cells in an aerobic and anoxic environment. Results: We found that the proton beam RBE for DSB induction at the tip of the Bragg peak, including primary and secondary particles, is close to 1.2. Furthermore, the RBE increases laterally to the beam axis at the area of Bragg peak. At the distal edge, the RBE is in the range from 1.3–1.4 for cells irradiated under aerobic conditions and may be as large as 1.5–1.8 for cells irradiated under anoxic conditions. Across the plateau region, the recorded RBE for DSB induction is 1.02 for aerobic cells and 1.05 for cells irradiated under anoxic conditions. The contribution to total effective dose from secondary heavy ions decreases with depth and is higher at shallow depths (e.g., at the surface of the skin). Conclusion: Multiscale simulation of the RBE for DSB induction provides useful insights into spatial variations in proton RBE within pristine Bragg peaks. This methodology is potentially useful for the biological optimization of proton therapy for the treatment of cancer. The study highlights the need to incorporate spatial variations in proton RBE into proton therapy treatment plans.« less
  • Purpose: Predicted PET images on the basis of analytical filtering approach for proton range verification has been successful developed and validated using FLUKA Monte Carlo (MC) codes and phantom measurements. The purpose of the study is to validate the effectiveness of analytical filtering model for proton range verification on GATE/GEANT4 Monte Carlo simulation codes. Methods: In this study, we performed two experiments for validation of predicted β+-isotope by the analytical model with GATE/GEANT4 simulations. The first experiments to evaluate the accuracy of predicting β+-yields as a function of irradiated proton energies. In second experiment, we simulate homogeneous phantoms of differentmore » materials irradiated by a mono-energetic pencil-like proton beam. The results of filtered β+-yields distributions by the analytical model is compared with those of MC simulated β+-yields in proximal and distal fall-off ranges. Results: The results investigate the distribution between filtered β+-yields and MC simulated β+-yields distribution in different conditions. First, we found that the analytical filtering can be applied over the whole range of the therapeutic energies. Second, the range difference between filtered β+-yields and MC simulated β+-yields at the distal fall-off region are within 1.5mm for all materials used. The findings validated the usefulness of analytical filtering model on range verification of proton therapy on GATE Monte Carlo simulations. In addition, there is a larger discrepancy between filtered prediction and MC simulated β+-yields using GATE code, especially in proximal region. This discrepancy might Result from the absence of wellestablished theoretical models for predicting the nuclear interactions. Conclusion: Despite the fact that large discrepancies of the distributions between MC-simulated and predicted β+-yields were observed, the study prove the effectiveness of analytical filtering model for proton range verification using GATE Monte Carlo simulation.« less
  • Purpose: To construct a dose monitoring system based on an endorectal balloon coupled to thin scintillating fibers to study the dose delivered to the rectum during prostate cancer proton therapy Methods: The Geant4 Monte Carlo toolkit version 9.6p02 was used to simulate prostate cancer proton therapy treatments of an endorectal balloon (for immobilization of a 2.9 cm diameter prostate gland) and a set of 34 scintillating fibers symmetrically placed around the balloon and perpendicular to the proton beam direction (for dosimetry measurements) Results: A linear response of the fibers to the dose delivered was observed within <2%, a property thatmore » makes them good candidates for real time dosimetry. Results obtained show that the closest fiber recorded about 1/3 of the dose to the target with a 1/r{sup 2} decrease in the dose distribution as one goes toward the frontal and distal top fibers. Very low dose was recorded by the bottom fibers (about 45 times comparatively), which is a clear indication that the overall volume of the rectal wall that is exposed to a higher dose is relatively minimized. Further analysis indicated a simple scaling relationship between the dose to the prostate and the dose to the top fibers (a linear fit gave a slope of −0.07±0.07 MeV per treatment Gy) Conclusion: Thin (1 mm × 1 mm × 100 cm) long scintillating fibers were found to be ideal for real time in-vivo dose measurement to the rectum for prostate cancer proton therapy. The linear response of the fibers to the dose delivered makes them good candidates of dosimeters. With thorough calibration and the ability to define a good correlation between the dose to the target and the dose to the fibers, such dosimeters can be used for real time dose verification to the target.« less
  • Purpose: To monitor the secondary dose distribution originating from a water phantom during proton therapy of prostate cancer using scintillating fibers. Methods: The Geant4 Monte Carlo toolkit version 9.6.p02 was used to simulate prostate cancer proton therapy based treatments. Two cases were studied. In the first case, 8 × 8 = 64 equally spaced fibers inside three 4 × 4 × 2.54 cmm{sup 3} DuPont™ Delrin blocks were used to monitor the emission of secondary particles in the transverse (left and right) and distal regions relative to the beam direction. In the second case, a scintillating block with a thicknessmore » of 2.54 cm and equal vertical and longitudinal dimensions as the water phantom was used. Geometrical cuts were used to extract the energy deposited in each fiber and the scintillating block. Results: The transverse dose distributions from secondary particles in both cases agree within <5% and with a very good symmetry. The energy deposited not only gradually increases as one moves from the peripheral row fibers towards the center of the block (aligned with the center of the prostate) but also decreases as one goes from the frontal to distal region of the block. The ratio of the doses from the prostate to the ones in the middle two rows of fibers showed a linear relationship with a slope (−3.55±2.26) × 10−5 MeV per treatment Gy. The distal detectors recorded a very small energy deposited due to water attenuation. Conclusion: With a good calibration and the ability to define a good correlation between the dose to the external fibers and the prostate, such fibers can be used for real time dose verification to the target.« less
  • Purpose: Accuracy in proton therapy treatment planning can be improved using Monte Carlo (MC) simulations. However the long computation time of such methods hinders their use in clinical routine. This work aims to develop a fast multipurpose Monte Carlo simulation tool for proton therapy using massively parallel central processing unit (CPU) architectures. Methods: A new Monte Carlo, called MCsquare (many-core Monte Carlo), has been designed and optimized for the last generation of Intel Xeon processors and Intel Xeon Phi coprocessors. These massively parallel architectures offer the flexibility and the computational power suitable to MC methods. The class-II condensed history algorithmmore » of MCsquare provides a fast and yet accurate method of simulating heavy charged particles such as protons, deuterons, and alphas inside voxelized geometries. Hard ionizations, with energy losses above a user-specified threshold, are simulated individually while soft events are regrouped in a multiple scattering theory. Elastic and inelastic nuclear interactions are sampled from ICRU 63 differential cross sections, thereby allowing for the computation of prompt gamma emission profiles. MCsquare has been benchmarked with the GATE/GEANT4 Monte Carlo application for homogeneous and heterogeneous geometries. Results: Comparisons with GATE/GEANT4 for various geometries show deviations within 2%–1 mm. In spite of the limited memory bandwidth of the coprocessor simulation time is below 25 s for 10{sup 7} primary 200 MeV protons in average soft tissues using all Xeon Phi and CPU resources embedded in a single desktop unit. Conclusions: MCsquare exploits the flexibility of CPU architectures to provide a multipurpose MC simulation tool. Optimized code enables the use of accurate MC calculation within a reasonable computation time, adequate for clinical practice. MCsquare also simulates prompt gamma emission and can thus be used also for in vivo range verification.« less