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Objective: A newly developed GafchromicTM EBT4 film model was released recently. According to the vendor‐stated specifications, this new model maintains major features of its more recent predecessor, EBT3, but has a great improvement in the signal‐to‐noise ratio (SNR). The purpose of this study was to fully characterize the EBT4 model by testing its dose response dependence on beam energy using clinical photon and electron beams and validating its improvement in SNR. Methods: In the beam energy dependence experiments, 6 MV and 15 MV photon beams, 6 MeV, 12 MeV and 20 MeV electron beams, 120 kVp and two 250 kVp x‐ray beams (with different half‐layer values) were selected, representing different clinical beam energies and radiation types. In the noise and SNR analyses, only the 6 MV photon beam was selected as the representative to compare between EBT4 and EBT3 models. Results: The energy dependence test results showed that there was a slight difference (<2% at most dose levels) in the dose response among the clinical MV photons and MeV electrons. However, a large deviation (>10%) in the dose response was found for the 120 kVp x‐ray beam. For the two 250 kVp x‐ray beams, the difference in the dose response was moderate (<5%), but not negligible. The noise and SNR results showed a reduced noise and strengthened SNR in EBT4. Conclusion: We conclude that the EBT4 film has a minimal energy dependence for MV photon and MeV electron beams but has a notable energy dependence for kilovoltage x‐ray beams, and the vendor‐stated features of the reduced noise and improved SNR in EBT4 are validated. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of dose calculation accuracy on inverse linear energy transfer (LET) optimization for intensity‐modulated proton therapy, and to determine whether adding more beams would improve the plan robustness to different dose calculation engines. Methods: Two sets of intensity‐modulated proton therapy plans using two, four, six, and nine beams were created for 10 prostate cancer patients: one set was optimized with dose constraints (DoseOpt) using the pencil beam (PB) algorithm, and the other set was optimized with additional LET constraints (LETOpt) using the Monte Carlo (MC) algorithm. Dose distributions of DoseOpt plans were then recalculated using the MC algorithm, and the LETOpt plans were recalculated using the PB algorithm. Dosimetric indices of targets and critical organs were compared between the PB and MC algorithms for both sets of plans. Results: For DoseOpt plans, dose differences between the PB and MC algorithms were minimal. However, the maximum dose differences in LETOpt plans were 11.11% and 15.85% in the dose covering 98% and 2% (D2) of the clinical target volume, respectively. Furthermore, the dose to 1 cc of the bladder differed by 11.42 Gy (relative biological effectiveness). Adding more beams reduced the discrepancy in target coverage, but the errors in D2 of the structure were increased with the number of beams. Conclusion: High modulation of LET requires high dose calculation accuracy during the optimization and final dose calculation in the inverse treatment planning for intensity‐modulated proton therapy, and adding more beams did not improve the plan robustness to different dose calculation algorithms. [ABSTRACT FROM AUTHOR]

Background: Reliable estimates of radiation dose to bone marrow are critical to understanding the risk of radiation‐induced cancers. Although the medical internal radiation dose phantom is routinely used for dose estimation, bone marrow is not defined in the phantom. Consequently, methods of indirectly estimating bone marrow dose have been implemented based on dose to surrogate volumes or average dose to soft tissue. Methods: In this study, new bone marrow structures were implemented and evaluated to the medical internal radiation dose phantom in Geant4, offering improved fidelity. The dose equivalent to the bone marrow was calculated across medical, occupational, and space radiation exposure scenarios, and compared with results using prior indirect estimation methods. Conclusion: Our results show that bone marrow dose may be overestimated by up to a factor of three when using the traditional methods when compared with the improved fidelity medical internal radiation dose method, specifically at clinical x‐ray energies. [ABSTRACT FROM AUTHOR]

The EBT‐XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared with its predecessor models. This characteristic has made EBT‐XD films suitable for high‐dose applications, such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra‐high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT‐XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot‐scanning proton beam was used to study LET dependence at three dose‐averaged LET values of 1.0 keV/μm, 3.6 keV/μm, and 7.6 keV/μm. A research proton beamline was used to study dose rate dependence at 150 Gy/s in the FLASH mode and 0.3 Gy/s in the non‐FLASH mode. Film response data from dose‐averaged LET values of 0.9 keV/μm and 9.0 keV/μm of the proton FLASH beam were also compared. Film response data from a clinical 6‐MV photon beam were used as a reference. Both the gray value method and optical density (OD) method were used in film calibration. Calibration results using a specific OD calculation method and a generic OD calculation method were compared. The four‐parameter NIH Rodbard function and three‐parameter rational function were compared in fitting the calibration curves. Experimental results showed that the response of EBT‐XD film is proton LET dependent, but independent of dose rate. Goodness‐of‐fit analysis showed that using the NIH Rodbard function is superior for both protons and photons. Using the "specific OD + NIH Rodbard function" method for EBT‐XD film calibration is recommended. [ABSTRACT FROM AUTHOR]

Purpose. To compare five techniques for the postmastectomy radiotherapy (PMRT) with simultaneous integrated boost (SIB). Materials and Methods. Twenty patients with left-sided breast cancer were retrospectively selected. Five treatment plans were created for each patient: TomoDirect (TD), unblocked helical TomoTherapy (unb-HT), blocked HT (b-HT), hybrid intensity-modulated radiotherapy (hy-IMRT), and fixed-field IMRT (ff-IMRT). A dose of 50.4 Gy in 28 fractions to PTVtotal and 60.2 Gy in 28 fractions to PTVboost were prescribed. The dosimetric parameters for targets and organs at risk (OARs), the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) for OARs, and the treatment efficiency were assessed and compared. Results. TD plans and hy-IMRT plans had similar good dose coverage and homogeneity for both PTVboost and PTVtotal and superior dose sparing for the lungs and heart. The ff-IMRT plans had similar dosimetric results for the target volumes compared with the TD and hy-IMRT plans, but gave a relatively higher NTCP and SCCP for the lungs. The unb-HT plans exhibited the highest OAR mean dose, highest NTCP for the lungs (0.97 ± 1.25 ‰) and heart (4.58 ± 3.62 %), and highest SCCP for the lungs (3.57 ± 0.05 %) and contralateral breast (2.75 ± 0.29 %) among all techniques. The b-HT plans significantly outperformed unb-HT plans with respect to the sparing of the lungs and heart. This technique also showed the best conformity index (0.73 ± 0.08) for PTVboost and the optimal NTCP for the lungs (0.03 ± 0.03 ‰) and heart (0.61 ± 0.73 %). Concerning the delivery efficiency, the hy-IMRT and ff-IMRT achieved much higher delivery efficiency compared with TomoTherapy plans. Conclusion. Of the five techniques studied, TD and hy-IMRT are considered the preferable options for PMRT with SIB for left-sided breast cancer treatment and can be routinely applied in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI)-guided radiotherapy is a promising image-guided cancer radiotherapy method. For MRI-guided radiotherapy, the proper energy of a therapeutic beam is important for beam-designing processes, and the magnetic-induced dose perturbation would be mainly influenced, especially the perturbation surrounding the tissue-air or air-tissue interfaces. Thus, it was necessary to investigate the impact of beam energy from photon, proton, and carbon ion beams on the magnetic-induced dose perturbations.Materials and Methods: Using a phantom of a water-air-water structure, the dose distributions were calculated with or without the presence of a 1.5 T uniform magnetic field through GEANT4. Based on the calculated doses, magnetic-induced dose perturbations were then obtained. For investigating the effects of beam energies on magnetic-induced dose perturbations, low-, middle-, and high-beam energies were adopted for each beam type.Results and Discussion: For photon beams, the dose perturbations were increased as the beam energies increased. At the up water-air interface, the maximum perturbations exceeded 50%. Near the edge of the radiation field, perturbations of 5%-20% were achieved. For proton and carbon ion beams, their Bragg peaks were shifted from original positions, and the shifting distances were increased with the increased beam energies. However, no evident magnetic-induced dose perturbations were noted at the up water-air interface and bottom air-water interface for all the beam energies. To some extent, this study provided references for assessing the effects of beam energies on magnetic-induced dose perturbations, especially the perturbations around the air cavities inside cancer patients.Conclusion: In MRI-guided cancer radiotherapy, the dose perturbation effects for therapeutic beams are relatively obvious, and the beam energies of therapeutic beams have large impacts on the magnetic-induced dose perturbations with the presence of a 1.5 T transverse magnetic field. [ABSTRACT FROM AUTHOR]

Background:The relative biological effectiveness (RBE) for particle therapy is a complex function of particle type, radiation dose, linear energy transfer (LET), cell type, endpoint, etc. In the clinical practice of proton therapy, the RBE is assumed to have a fixed value of 1.1. This assumption, along with the effects of physical uncertainties, may mean that the biologically effective dose distributions received by the patient may be significantly different from what is seen on treatment plans. This may contribute to unforeseen toxicities and/or failure to control the disease. Variability of Proton RBE:It has been shown experimentally that proton RBE varies significantly along the beam path, especially near the end of the particle range. While there is now an increasing acceptance that proton RBE is variable, there is an ongoing debate about whether to change the current clinical practice. Clinical Evidence:A rationale against the change is the uncertainty in the models of variable RBE. Secondly, so far there is no clear clinical evidence of the harm of assuming proton RBE to be 1.1. It is conceivable, however, that the evidence is masked partially by physical uncertainties. It is, therefore, plausible that reduction in uncertainties and their incorporation in the estimation of dose actually delivered may isolate and reveal the variability of RBE in clinical practice. Nevertheless, clinical evidence of RBE variability is slowly emerging as more patients are treated with protons and their response data are analyzed. Modelling and Incorporation of RBE in the Optimization of Proton Therapy:The improvement in the knowledge of RBE could lead to better understanding of outcomes of proton therapy and in the improvement of models to predict RBE. Prospectively, the incorporation of such models in the optimization of intensity-modulated proton therapy could lead to improvements in the therapeutic ratio of proton therapy. [ABSTRACT FROM AUTHOR]

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using GEANT4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 µm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT4. The incorrect LETd values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 µm, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 μm, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive. [ABSTRACT FROM AUTHOR]

Simple Summary: Although particle therapy using protons and heavier ions has many inherent advantages when compared to x-rays for cancer treatment, numerous unknowns still exist in the radiobiology of particle therapy. Informative high-accuracy biological effects data are lacking and difficult to obtain. This study aimed to provide a novel high-throughput experimental method to more efficiently obtain large amounts of biophysical data of particle therapy and to correlate the biological responses with the physical characteristics of particle beams. Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific. [ABSTRACT FROM AUTHOR]

To theoretically explore the feasibility of neutron dose characterized by Cerenkov photons, the relationship between Cerenkov photons and neutron dose in a water phantom was quantified using the Monte Carlo toolkit Geant4. Results showed that the ratio of the neutron dose deposited by secondary electrons above Cerenkov threshold energy to the total neutron dose is approximately a constant for monoenergetic neutrons from 0.01 eV to 100 eV. With the initial neutron beam energy from 0.01 eV to 100 eV, the number of Cerenkov photons has a good correlation with the total neutron dose along the central axis of the water phantom. The changes of neutron energy spectrum and mechanism analysis also explored at different depths. And the ratio of total neutron dose to the intensity of Cerenkov photons is independent of neutron energy for neutrons from 0.01 eV to 100 eV. These findings indicate that Cerenkov radiation also has potential in the application of neutron dose measurement in some specific fields. [ABSTRACT FROM AUTHOR]

Purpose: We introduce a methodology to calculate the microdosimetric quantity dose-mean lineal energy for input into the microdosimetric kinetic model (MKM) to model the relative biological effectiveness (RBE) of proton irradiation experiments.Methods and Materials: The data from 7 individual proton RBE experiments were included in this study. In each experiment, the RBE at several points along the Bragg curve was measured. Monte Carlo simulations to calculate the lineal energy probability density function of 172 different proton energies were carried out with use of Geant4 DNA. We calculated the fluence-weighted lineal energy probability density function (fw(y)), based on the proton energy spectra calculated through Monte Carlo at each experimental depth, calculated the dose-mean lineal energy yD¯ for input into the MKM, and then computed the RBE. The radius of the domain (rd) was varied to reach the best agreement between the MKM-predicted RBE and experimental RBE. A generic RBE model as a function of dose-averaged linear energy transfer (LETD) with 1 fitting parameter was presented and fit to the experimental RBE data as well to facilitate a comparison to the MKM.Results: Both the MKM and LETD-based models modeled the RBE from experiments well. Values for rd were similar to those of other cell lines under proton irradiation that were modeled with the MKM. Analysis of the performance of each model revealed that neither model was clearly superior to the other.Conclusions: Our 3 key accomplishments include the following: (1) We developed a method that uses the proton energy spectra and lineal energy distributions of those protons to calculate dose-mean lineal energy. (2) We demonstrated that our application of the MKM provides theoretical validation of proton irradiation experiments that show that RBE is significantly greater than 1.1. (3) We showed that there is no clear evidence that the MKM is better than LETD-based RBE models. [ABSTRACT FROM AUTHOR]