[en] Full text: Particle therapy has many advantages over conventional photon therapy, particularly for treating deep-seated solid tumours due to its greater conformal energy deposition achieved by the Bragg peak (BP). Successful treatment with protons and heavy ions depends largely on knowledge of the relative biological effectiveness (RBE) of the radiation produced by primary and secondary charged particles. Similarly to heavy ion therapy, in deep space environments, where high energy heavy ions are observed, their linear energy transfer (LET) spectrum is important to be characterized and monitored due to their adverse effects on human health as well as electronic components. Microdosimetry involves the measurement of the energy deposition spectrum in micro-sized volumes and from this measured spectrum both the biological and electronic impact from the radiation field can be predicted. Microdosimetric measurements are traditionally performed using tissue equivalent proportion counters (TEPCs). However, due to their poor spatial resolution they are not well suited to the sharp dose gradients associated with the distal edge of the BP. Additionally, due to their bulky size and complex operation make them challenging for onboard spacecraft use. To address the drawbacks of TEPCs, the Centre for Medical Radiation Physics (CMRP) has developed silicon-on-insulator (SOI) microdosimeters over many years. The latest CMRP SOI microdosimeters are called the “Bridge” and “Mushroom”, both have fully 3D micron sized sensitive volumes (SVs), mimicking the dimensions of cells. The silicon microdosimeters provide extremely high spatial resolution and were used to measure the dose mean lineal energy and estimate the RBE₁₀ using the microdosimetric kinetic model (MKM) for 290 MeV/u ¹²C, 180 MeV/u ¹⁴N and 400 MeV/u ¹⁶O ions at Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. The SOI microdosimeters have also been used to measure the LET of different ions with low energies at the ANU Heavy Ion accelerator including 52 MeV ⁷Li, 70 MeV ¹²C, 118 MeV ¹⁶O and 170 MeV ⁴⁸Ti. The study of LET at ANU was to determine the applicability of silicon microdosimeters for high LET ions typical of space. Good agreement between the measured LET was observed with Geant4 and SRIM calculations. This confirmed that the CMRP SOI microdosimeters are not affected by plasma recombination up to LETs of approximately 1300 keV/μm in Si. The microdosimetric spectra obtained for low energy ¹²C and ¹⁶O ions were compared to the microdosimetric spectra measured at the distal part of the Bragg peak for therapeutic ¹²C and ¹⁶O ion beam that allows separate the contributions of the primary ion beam and secondaries. The measurements performed over the years with the CMRP SOI devices have shown that they are well suited for characterising heavy ion therapy beam and for low energy heavy ions typical for space radiation environment inside of spacecrafts. (author)

[en] ¹²C ion therapy has had growing interest in recent years for its excellent dose conformity. However at therapeutic energies, which can be as high as 400 MeV/u, carbon ions produce secondary fragments. For an incident 400 MeV/u ¹²C ion beam, ~70% of the beam will undergo fragmentation before the Bragg Peak. The dosimetric and radiobiological impact of these fragments must be accurately characterised, as it can result in increasing the risk of secondary cancer for the patient as well as altering the relative biological effectiveness. Here, this work investigates the accuracy of three different nuclear fragmentation models available in the Monte Carlo Toolkit Geant4, the Binary Intranuclear Cascade (BIC), the Quantum Molecular Dynamics (QMD) and the Liege Intranuclear Cascade (INCL++). The models were benchmarked against experimental data for a pristine 400 MeV/u ¹²C beam incident upon a water phantom, including fragment yield, angular and energy distribution. For fragment yields the three alternative models agreed between ~5 and ~35% with experimental measurements, the QMD using the “Frag” option gave the best agreement for lighter fragments but had reduced agreement for larger fragments. For angular distributions INCL++ was seen to provide the best agreement among the models for all elements with the exception of Hydrogen, while BIC and QMD was seen to produce broader distributions compared to experiment. BIC and QMD performed similar to one another for kinetic energy distributions while INCL++ suffered from producing lower energy distributions compared to the other models and experiment.

[en] Particle therapy has many advantages over conventional photon therapy, particularly for treating tumours near high risk organs, due to its greater conformal energy deposition achieved in the form of the Bragg Peak (BP). One significant current clinical application of particle therapy is ocular proton therapy. The physical characteristics of proton therapy allows for uniform dose distribution, minimal scatter, and sharp dose fall off making it an ideal therapy for ocular tumours. This allows for high radiation dose delivery with relative sparing of adjacent high-risk organs. Successful treatment with heavy ions depends largely on knowledge of the relative biological effectiveness (RBE) of the radiation produced by primary and secondary charged particles. Different methods and approaches are used for calculation of the RBE-weighted absorbed dose in treatment planning system (TPS) for proton therapy. In the course of this research, a new 3D SV microdosimeter has been used to conduct an infield and out of field microdosimetric study of an ocular proton therapy beam located at the CATANA (Centro di AdroTerapia Applicazioni Nucleari Avanzate) facility in Catania, Italy. (author)

[en] Nuclear fragmentation produced in ¹²C ion therapeutic beams contributes significantly to the Relative Biological Effectiveness (RBE)—weighted dose in the distal edge of the Spread out Bragg Peak (SOBP) and surrounding tissues in out-of-field. Complex mixed radiation field originated by the therapeutic ¹²C ion beam in a phantom is difficult to measure. This study presents a new method to characterise the radiation field produced in a ¹²C ion beam using a monolithic $\Delta$E-E telescope which provides the capability to identify the particle components of the mixed radiation field as well as the microdosimetric spectra that allows derivation of the RBE based on a radiobiological model. The response of the monolithic $\Delta$E-E telescope to a 290 MeV/u ¹²C ion beam at defined positions along the pristine Bragg Peak was studied using the Geant4 Monte Carlo toolkit. The microdosimetric spectra derived from the $\Delta$E stage and the two-dimensional scatter plots of energy deposition in $\Delta$E and E stages of the device in coincidence are presented, as calculated in-field and out-of-field. Partial dose weighted contribution to the microdosimetric spectra from nuclear fragments and recoils, such as ¹H, ⁴He, ³He, ⁷Li, ⁹Be and ¹¹B, have been analysed for each position. Comparison of simulation and experimental results are presented and demonstrates that the microdosimetric spectra changes dramatically within 0.5 mm depth increments close to and at the distal edge of the Bragg Peak which is impossible to identify using conventional Tissue Equivalent Proportional Counter (TEPC).

[en] Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic ¹²C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length $⟨<!--\; ???\; -->l_{\text{Path}}⟩<!--\; ???\; -->$ to calculate the lineal energy was introduced as an alternative to the mean chord length $⟨<!--\; ???\; -->l⟩<!--\; ???\; -->$ because it was found that adopting Cauchy’s formula for the $⟨<!--\; ???\; -->l⟩<!--\; ???\; -->$ was not appropriate for the radiation field typical of HIT as it is very directional. $⟨<!--\; ???\; -->l_{\text{Path}}⟩<!--\; ???\; -->$ can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident ¹²C ion beam can be adopted as $⟨<!--\; ???\; -->l_{\text{Path}}⟩<!--\; ???\; -->$. The tissue equivalence conversion method and $⟨<!--\; ???\; -->l_{\text{Path}}⟩<!--\; ???\; -->$ were adopted to determine the RBE₁₀, calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE₁₀ along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of the determination of $⟨<!--\; ???\; -->l_{\text{Path}}⟩<!--\; ???\; -->$. (paper)

[en] Heavy-particle therapy such as carbon ion therapy is currently very popular because of its superior conformality in terms of dose distribution and higher Relative Biological Effectiveness (RBE). However, carbon ion beams produce a complex mixed radiation field, which needs to be fully characterised. In this study, the fragmentation of a 290 MeV/u primary carbon ion beam was studied using the Geant4 Monte Carlo Toolkit. When the primary carbon ion beam interacts with water, secondary light charged particles (H, He, Li, Be, B) and fast neutrons are produced, contributing to the dose, especially after the distal edge of the Bragg peak. (paper)

[en] A feasibility study is presented on a newly developed microdosimetry system named Octobox, for its application in low dose rate, mixed radiation environments. A full characterization of the device was performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan, out-of-field of various heavy ion radiation fields — 290 MeV/u ¹²C, 230 MeV/u and 490 MeV/u ²⁸Si and 400 MeV/u ²⁰Ne ions, as well as a low dose rate ²²²Rn environment at the Australian Nuclear Sciences and Technology Organization (ANSTO). The device was shown to collect adequate statistics in a short period of time when compared to the MicroPlus probe with a single microdosimeter, while accurately measuring microdosimetric quantities and the corresponding average quality factor ($\overline{Q}$) and dose equivalent (H) of the mixed radiation field. Good agreement of the microdosimetric spectra was also shown with Geant4 simulations for all presented ion fields. Based on the findings in this study, the Octobox is capable of being applied in mixed, low dose rate, radiation environments such as those encountered in space and aviation, as well as in underground mines for radiation protection purposes.

[en] Highlights: • Auger electrons can deliver dose locally to the radiation sensitive targets. • The emission of Auger electrons in Geant4. • The Auger electrons are alternative channel to X-ray fluorescence. • Geant4 is extensively used in medical physics applications. • Geant4 in terms of emission of Auger electrons. Auger emitting radioisotopes are of great interest in targeted radiotherapy because, once internalised in the tumour cells, they can deliver dose locally to the radiation sensitive targets, while not affecting surrounding cells. Geant4 is a Monte Carlo code widely used to characterise the physics mechanism at the basis of targeted radiotherapy. In this work, we benchmarked the modelling of the emission of Auger electrons in Geant4 deriving from the decay of ¹²³I, ¹²⁴I, ¹²⁵I radionuclides against existing theoretical approaches. We also compared Geant4 against reference data in the case of ¹³¹Cs, which is of interest for brachytherapy. In the case of ¹²⁵I and ¹³¹Cs, the simulation results are compared to experimental measurements as well. Good agreement was found between Geant4 and the reference data. As far as we know, this is the first study aimed to benchmark against experimental measurements the emission of Auger electrons in Geant4 for radiotherapy applications.

[en] In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm³, treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases. (paper)

[en] A new methodology for assessing linear energy transfer (LET) and relative biological effectiveness (RBE) in proton therapy beams using thermoluminescent detectors is presented. The method is based on the different LET response of two different lithium fluoride thermoluminescent detectors (LiF:Mg,Ti and LiF:Mg,Cu,P) for measuring charged particles. The relative efficiency of the two detector types was predicted using the recently developed Microdosimetric d(z) Model in combination with the Monte Carlo code PHITS. Afterwards, the calculated ratio of the expected response of the two detector types was correlated with the fluence- and dose- mean values of the unrestricted proton LET. Using the obtained proton dose mean LET as input, the RBE was assessed using a phenomenological biophysical model of cell survival.

The aforementioned methodology was benchmarked by exposing the detectors at different depths within the spread out Bragg peak (SOBP) of a clinical proton beam at iThemba LABS. The assessed LET values were found to be in good agreement with the results of radiation transport computer simulations performed using the Monte Carlo code GEANT4. Furthermore, the estimated RBE values were compared with the RBE values experimentally determined by performing colony survival measurements with Chinese Hamster Ovary (CHO) cells during the same experimental run. A very good agreement was found between the results of the proposed methodology and the results of the in vitro study. (paper)