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At least 667 records · Page 37

TU-C-17A-12: Towards a Passively Optimized Phase-Space Monte Carlo (POPMC) Treatment Planning Method: A Proof of Principle

Purpose: The advent of on-line/off-line adaptive, and biologically-conformal radiation therapy has led to a need for treatment planning solutions that utilize voxel-specific penalties, requiring optimization over a large solution space that is performed quickly, and the dose in each voxel calculated accurately. This work proposes a “passive” optimization framework, which is executed concurrently during Monte Carlo dose calculation, evaluating the cost/benefit of each history during transport, and creates a passively optimized fluence map. Methods: The Monte Carlo code Geant4 v9.6 was used for this study. The standard voxel geometry implementation was modified to support the passive optimization framework, with voxel-specific optimization parameters. Dose-benefit functions, which will increase a particle history’s weight upon dose deposition, were defined in a central collection of voxels to effectively create target structures. Histories that deposit energy to voxels are reweighted based on a voxel’s dose multiplied by its cost/benefit value. Upon full termination of each history, the dose contributions of that history are reweighted to reflect a contribution proportional to the history’s final weight. A parallel-planar 1.25 MeV photon fluence is transported through the geometry, and re-weighted at each dose deposition step. The resulting weight is tallied with the incident spatial and directional coordinates in a phase-space distribution. Results: A uniform incident fluence was reweighted during MC dose calculations to create an optimized fluence map which would generate dose profiles in target volumes that exhibit the same dose characteristics as the prescribed optimization parameters. An optimized dose profile, calculated concurrently with the phase-space, reflects the resulting dose distribution. Conclusion: This study demonstrated the feasibility of passively optimizing an incident fluence map during Monte Carlo dose calculations. The flexibility of the voxel-specific optimization framework allows a variety and combination of optimization parameters to be calculated for each voxel at every transportation step. This work is partially supported by Varian. This work is partially supported by the NIH.

07 ISOTOPE AND RADIATION SOURCES↗

MO-D-213-04: The Proximity to the Skin of PTV Affects PTV Coverage and Skin Dose for TomoTherapy

Purpose: The proximity to the skin surface of the PTV for the patients with skin disease could be a concern in terms of the PTV coverage and actual surface dose (SD). IMRT optimization algorithms increase the beam intensity close to the skin in order to compensate for lack of scattering material, leading to enhanced SD but potential hot spots. This study aims to investigate the effect of PTV proximity to the skin on planning and measured SD Methods: All measurements were done for 6 MV X-ray beam of Helical TomoTherapy. An anthropomorphic phantom was scanned in a CT simulator in a routine manner with thermoplastic mask immobilization. PTVs were created with varying distances to the skin of 0 mm -(PTV1), 1 mm- (PTV2), 2 mm-(PTV3) and 3 mm-(PTV4). Also, a 5 mm bolus was used with PTV1 (PTV5). All planning constraints were kept the same in all studies (hard constraint: 95% of the prescription dose covered 95% of the PTV). Gafchromic film (EBT3) was placed under the mask on the phantom surface, and the resulting dose was estimated using RIT software. Results: Optimizing the dose using different PTVs lead to average planned target doses of 10.8, 10.3, 10.2, 10.3 and 10.0 Gy, with maximum doses 12.2, 11.2, 11.1, 11.1 and 10.0 Gy for PTV1, PTV2, PTV3, PTV4 and PTV5, respectively. EBT3 measurements indicated a significant decrease of SD with skin distance by 12.7% (PTV1), 21.9% (PTV2), 24.8% (PTV3) and 28.4% (PTV4) comparing to prescription dose. Placement of a 5 mm bolus on the phantom surface resulted in a SD close to prescribed (+0.5%). Conclusion: This work provides a clear demonstration of the relationship between the skin dose and the PTV to the skin distance. The results indicate the necessity of a bolus even for TomoTherapy when high skin dose is required.

60 APPLIED LIFE SCIENCES↗

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, less EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-F-T-218: Validation of An In-Vivo Proton Range Verification Method for Reducing the Risk of Permanent Alopecia in the Treatment of Pediatric Medulloblastoma

Purpose: The clinical commissioning of a workflow for pre-treatment range verification/adjustment for the head treatment of pediatric medulloblastoma patients, including dose monitoring during treatment. Methods: An array of Si-diodes (DIODES Incorporated) is placed on the patient skin on the opposite side to the beam entrance. A “scout” SOBP beam, with a longer beam range to cover the diodes in its plateau, is delivered; the measured signal is analyzed and the extracted water equivalent path lengths (WEPL) are compared to the expected values, revealing if a range correction is needed. Diodes stay in place during treatment to measure dose. The workflow was tested in solid water and head phantoms and validated against independent WEPL measurements. Both measured WEPL and skin doses were compared to computed values from the TPS (XiO); a Markus chamber was used for reference dose measurements. Results: The WEPL accuracy of the method was verified by comparing it with the dose extinction method. It resulted, for both solid water and head phantom, in the sub-millimeter range, with a deviation less than 1% to the value extracted from the TPS. The accuracy of dose measurements in the fall-off part of the dose profile was validated against the Markus chamber. The entire range verification workflow was successfully tested for the mock-treatment of head phantom with the standard delivery of 90 cGy per field per fraction. The WEPL measurement revealed no need for range correction. The dose measurements agreed to better than 4% with the prescription dose. The robustness of the method and workflow, including detector array, hardware set and software functions, was successfully stress-tested with multiple repetitions. Conclusion: The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification with acceptable dose to the patient.

60 APPLIED LIFE SCIENCES↗

Neutron-Irradiated Samples as Test Materials for MPEX

Plasma Material Interaction (PMI) is a major concern in fusion reactor design and analysis. The Material-Plasma Exposure eXperiment (MPEX) will explore PMI under fusion reactor plasma conditions. Samples with accumulated displacements per atom (DPA) damage produced by fast neutron irradiations in the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL) will be studied in the MPEX facility. This paper presents assessments of the calculated induced radioactivity and resulting radiation dose rates of a variety of potential fusion reactor plasma-facing materials (such as tungsten). The scientific code packages MCNP and SCALE were used to simulate irradiation of the samples in HFIR including the generation and depletion of nuclides in the material and the subsequent composition, activity levels, gamma radiation fields, and resultant dose rates as a function of cooling time. A challenge of the MPEX project is to minimize the radioactive inventory in the preparation of the samples and the sample dose rates for inclusion in the MPEX facility.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

A fast Monte Carlo cell-by-cell simulation for radiobiological effects in targeted radionuclide therapy using pre-calculated single-particle track standard DNA damage data

Introduction: We developed a new method that drastically speeds up radiobiological Monte Carlo radiation-track-structure (MC-RTS) calculations on a cell-by-cell basis. Methods: The technique is based on random sampling and superposition of single-particle track (SPT) standard DNA damage (SDD) files from a “pre-calculated” data library, constructed using the RTS code TOPAS-nBio, with “time stamps” manually added to incorporate dose-rate effects. This time-stamped SDD file can then be input into MEDRAS, a mechanistic kinetic model that calculates various radiation-induced biological endpoints, such as DNA double-strand breaks (DSBs), misrepairs and chromosomal aberrations, and cell death. As a benchmark validation of the approach, we calculated the predicted energy-dependent DSB yield and the ratio of direct-to-total DNA damage, both of which agreed with published in vitro experimental data. We subsequently applied the method to perform a superfast cell-by-cell simulation of an experimental in vitro system consisting of neuroendocrine tumor cells uniformly incubated with 177 Lu. Results and discussion: The results for residual DSBs, both at 24 and 48 h post-irradiation, are in line with the published literature values. Our work serves as a proof-of-concept demonstration of the feasibility of a cost-effective “in silico clonogenic cell survival assay” for the computational design and development of radiopharmaceuticals and novel radiotherapy treatments more generally.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Challenges and Opportunities Specific to Microreactors: Compact and Light-Weight Shielding During Operation and Transportation

The problem of designing a shield for a mobile microreactor has been addressed. The principal challenges encountered in this endeavor are the dual goals of increasing radiation protection and decreasing weight. It is recognized that these two goals are contradictory. Increasing shielding naturally increases weight. Conversely, decreasing weight naturally calls for decreasing material inventory, including possibly decreasing shield mass. The operational and regulatory drivers for shielding and transportation constraints are identified and summarized. The main constraints pertain to volume, mass, radiation dose, material feasibility and availability, and decommissioning expectations. The latter are limits on residual contamination and dose rates after the reactor is removed. Progress toward solving the challenge of shielding a transportable microreactor is made by considering a tungsten tetraboride (WB4) shell surrounding the reactor vessel. The shield and a generic microreactor were modeled using the MCNP code. It was determined that the presence of a 16-cm-thick WB4 shield reduces the dose equivalent rate during operations to 3.6 mrem/h just outside of a concrete vault and dome and soil berm surrounding the reactor, which is very near the occupational dose rate limits. Without the WB4 layer, the dose rate at the same location outside the berm would be 120 mrem/h. Most importantly, the presence of the WB4 shield substantially protects the surrounding concrete and soil from activation, thus decreasing the duration of administrative control for the site following removal of the reactor from 16 to 3.4 years. At that point, the site may be decommissioned and returned to unrestricted public access. A limitation on the incorporation of a WB4 shield as an intrinsic component of a microreactor is that it results in a design that is transportable only by using the largest road conveyances and that the load would require special permits for transit through the U.S. highway system. New directions for further improvements and possibly more effective solutions to the shielding problem of a mobile microreactor are discussed in the conclusion section.

Microreactor↗

MatMCNP: A Code for Producing Material Cards for MCNP

A code for generating MCNP material cards (MatMCNP) has been written and verified for naturally occurring, stable isotopes. The program allows for material specification as either atomic or weight percent (fractions). MatMCNP also permits the specification of enriched lithium, boron, and/or uranium. In addition to producing the material cards for MCNP, the code calculates the atomic (or number) density in atoms/barn-cm as well as the multiplier that should be used to convert neutron and gamma fluences into dose in the material specified.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

LLNL NESHAPs Radionuclide Air Emission Report for 2011 (2011 Annual Report)

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) where radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 µSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 1.0, to calculate the dose to the maximally exposed individual member of the public for the Livermore site and Site 300.

54 ENVIRONMENTAL SCIENCES↗

Lawrence Livermore National Laboratory National Emission Standards for Hazardous Air Pollutants (NESHAPs) 2012 Annual Report

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) where radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 µSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 1.0, to calculate the dose to the maximally exposed individual member of the public for the Livermore site and Site 300.

54 ENVIRONMENTAL SCIENCES↗

LLNL NESHAPs 2009 Annual Report

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) where radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 μSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 1.0, to calculate the dose to the maximally exposed individual for the Livermore site and Site 300. The dose for the LLNL site-wide maximally exposed members of the public from operations in 2009 are summarized here: Livermore site: 0.0042 mrem (0.042 μSv) (36% from point source emissions, 64% from diffuse source emissions). The point source emissions include gaseous tritium modeled as tritiated water vapor as directed by EPA Region IX; the resulting dose is used for compliance purposes; Site 300: 2.7 × 10 -7 mrem (2.7 × 10 -6 μSv) (100% from point source emissions).

54 ENVIRONMENTAL SCIENCES↗

Lawrence Livermore National Laboratory Radionuclide Air Emission Report for 2013 (NESHAPs 2013 Annual Report)

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) where radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 μSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 4.0.0.570, to calculate the dose to the maximally exposed individual member of the public for the Livermore Site and Site 300.

54 ENVIRONMENTAL SCIENCES↗

LLNL NESHAPs 2015 Annual Report - June 2016

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) in which radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 μSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 4.0.1.17, to calculate the dose to the maximally exposed individual member of the public for the Livermore Site and Site 300.

54 ENVIRONMENTAL SCIENCES↗

NESHAPs CY19 Report: Radionuclide Air Emission Report for 2019

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) in which radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 μSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 4.0.1.17, to calculate the dose to the maximally exposed individual member of the public for the Livermore Site and Site 300. In 2019, LLNL maintained its compliance with 40 CFR 61, Subpart H. All radioactive air emissions resulted in calculated doses far below the annual 10 mrem (100 μSv) sitewide standard. The annual doses to the site-wide maximally exposed individual member of the public at the Livermore Site and Site 300 from planned and unplanned operations in 2019 are: Livermore Site: 4.3 x 10⁻³ mrem (4.3 x 10⁻² μSv); Site 300: 9.5 x 10⁻⁸ mrem (9.5 x 10⁻⁷ μSv).

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

LLNL NESHAPs 2023 Annual Report

Lawrence Livermore National Security, LLC operates facilities at Lawrence Livermore National Laboratory (LLNL) in which radionuclides are handled and stored. These facilities are subject to the U.S. Environmental Protection Agency (EPA) National Emission Standards for Hazardous Air Pollutants (NESHAPs) in Code of Federal Regulations (CFR) Title 40, Part 61, Subpart H, which regulates radionuclide emissions to air from Department of Energy (DOE) facilities. Specifically, NESHAPs limits the emission of radionuclides to the ambient air to levels resulting in an annual effective dose equivalent of 10 mrem (100 µSv) to any member of the public. Using measured and calculated emissions, and building-specific and common parameters, LLNL personnel applied the EPA-approved computer code, CAP88-PC, Version 4.1.1.0, to calculate the dose to the maximally exposed individual member of the public for the Livermore Site and Site 300.

54 ENVIRONMENTAL SCIENCES↗

SU-E-T-381: Evaluation of Calculated Dose Accuracy for Organs-At-Risk Located at Out-Of-Field in a Commercial Treatment Planning System for High Energy Photon Beams Produced From TrueBeam Accelerators

Purpose: Dose calculation accuracy for the out-of-field dose is important for predicting the dose to the organs-at-risk when they are located outside primary beams. The investigations on evaluating the calculation accuracy of treatment planning systems (TPS) on out-of-field dose in existing publications have focused on low energy (6MV) photon. This study evaluates out-of-field dose calculation accuracy of AAA algorithm for 15MV high energy photon beams. Methods: We used the EGSnrc Monte Carlo (MC) codes to evaluate the AAA algorithm in Varian Eclipse TPS (v.11). The incident beams start with validated Varian phase-space sources for a TrueBeam linac equipped with Millennium 120 MLC. Dose comparisons between using AAA and MC for CT based realistic patient treatment plans using VMAT techniques for prostate and lung were performed and uncertainties of organ dose predicted by AAA at out-of-field location were evaluated. Results: The results show that AAA calculations under-estimate doses at the dose level of 1% (or less) of prescribed dose for CT based patient treatment plans using VMAT techniques. In regions where dose is only 1% of prescribed dose, although AAA under-estimates the out-of-field dose by 30% relative to the local dose, it is only about 0.3% of prescribed dose. For example, the uncertainties of calculated organ dose to liver or kidney that is located out-of-field is <0.3% of prescribed dose. Conclusion: For 15MV high energy photon beams, very good agreements (<1%) in calculating dose distributions were obtained between AAA and MC. The uncertainty of out-of-field dose calculations predicted by the AAA algorithm for realistic patient VMAT plans is <0.3% of prescribed dose in regions where the dose relative to the prescribed dose is <1%, although the uncertainties can be much larger relative to local doses. For organs-at-risk located at out-of-field, the error of dose predicted by Eclipse using AAA is negligible. This work was conducted in part using the resources of Varian research grant VUMC40590-R.

60 APPLIED LIFE SCIENCES↗

SU-F-T-586: Pre-Treatment QA of InCise2 MLC Plans On a Cyberknife-M6 Using the Delta4 System in SBRT

Purpose: Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). Methods: In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed using a 10×10 cm{sup 2} field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. Results: All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. Conclusion: Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.

60 APPLIED LIFE SCIENCES↗

Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local dose enhancement and how more realistic configurations lead to a negligible increase of local energy deposition. The obtained dose enhancement factor was up to 1.7 when the source was located at the nanoparticle surface. This dose enhancement was reduced when the source was located at further distances (i.e., in more realistic situations). Additionally, no significant increase in the dissociative electron attachment processes was observed. Conclusions: The authors’ results indicate that physical effects play a minor role in the amplification of damage, as a very low dose enhancement or increase of dissociative electron attachment processes is observed when the authors get closer to more realistic simulations. Thus, other effects, such as biological or chemical processes, may be mainly responsible for the enhanced radiosensibilization observed in biological studies. However, more biological studies are needed to verify this hypothesis.

60 APPLIED LIFE SCIENCES↗