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Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper. [ABSTRACT FROM AUTHOR]

Thermoluminescence (TL) dosimetry relies on evaluating the dose absorbed in the TL detector by measuring the light output by the detector, i.e. by the TL glow-curve analysis. However, the absolute efficiency of the TL light emission per unit dose of ionizing radiation absorbed in the detector is known to depend on the energy and quality (ionization density) of this radiation. Moreover, as the TL light is absorbed in the detector itself, the spatial distribution of energy deposition events inside the detector also needs to be considered. It is convenient to describe the response of the detector (TL output per unit dose) relative to that after a dose of sparsely ionizing reference radiation, such as 137Cs γ-rays, via relative efficiency, ηiγ, defined as the TL light signal emitted by the TL detector per unit imparted energy of radiation of the type i, normalized to the signal per unit imparted energy of this reference radiation. Microdosimetric models have provided an insight as to the variation of ηiγ, with the energy and ionization density, related to the spatial distribution of ionizations and excitations produced by the ionizing radiation in the detector, as well as some experimental factors related to the TL light transport within the detector. To study the variation of ηiγ with LET in LiF:Mg, Ti detectors irradiated by heavy charged particles (high-LET radiation), the most successful approach was the track structure model, based on the radial distribution of dose (RDD) around the ion tracks. For low-LET radiation (photons, electrons) the microdosimetric model has been successfully applied to predict ηiγ for LiF:Mg,Ti, LiF:Mg,Cu,P, and CaF2:Tm TL detectors, to explain the discrepancy between the measured and predicted photon-energy response of these detectors. [Copyright &y& Elsevier]

The microdosimetric one-hit detector model has been developed and applied to calculate the dose response, energy response and relative efficiency of thermoluminescent LiF:Mg,Cu,P and CaF2:Tm detectors, and of the free-radical alanine dosimeter, after their exposure to radiation of different quality. The one-hit detector is described by two model parameters: the target diameter, d and the saturation parameter, α. Combining these parameters with microdosimetric distributions in nanometer-size targets calculated using Monte Carlo track structure codes TRION and MOCA-14, it was possible to describe and predict a great variety of experimental data for photon, X-ray, beta-electron, proton, alpha-particles and heavy ion irradiation. Within the framework of this biophysical model of radiation action, some mechanistic insight into the physics of radiation action in solid state detectors can be obtained. [Copyright &y& Elsevier]

Microbeam radiation therapy (MRT) is an irradiation modality for therapeutic purposes which uses arrays of collimated quasi parallel microbeams, each up to 100 μm wide, to deliver high radiation doses. Several studies have reported the extraordinary tolerance of normal tissues to MRT irradiation; conversely, MRT has been shown to be highly efficient on tumor growth control. The original and most widely developed application of MRT, yet in the preclinical phase, consists in using spatially fractionated X-ray beams issued from a synchrotron radiation source in the treatment of brain tumors. More recently, MRT has been tested in successful pioneering assays to reduce or interrupt seizures in preclinical models of epilepsy. The MRT concept has also been extended to proton therapy. The development of MRT towards its clinical implementation is presently driven by an EU-supported consortium of laboratories from 16 countries within the COST Action TD1205 (SYRA3). The results of the first SYRA3 workshop on “Radiation Therapy with Synchrotron Radiation: Achievements and Challenges” held in Krakow (Poland) during March 25–26 2014 are summarized in this issue with an overview presented in this paper. The papers reflect the multidisciplinary international activities of SYRA3. The topics covered in this focus issue include medical physics aspects, pre-clinical studies, clinical applications, and an industrial perspective; finally an outlook towards future prospects of compact sources and proton microbeams. [ABSTRACT FROM AUTHOR]

The Microdosimetric d(z) Model was used in combination with simulated microdosimetric specific energy probability distributions for monoenergetic 1H and 4He ions (energy range = 0.1–1000 MeV/n, target size range = 1–2000 nm) to investigate the possibility of modeling the relative efficiency of two optical absorption (OA) bands (4.77 and 5.08 eV) in the OA energy spectra of LiF:Mg,Ti (TLD-100) thermoluminescent detectors. This work represents the first application of the model to a physical system other than thermally- and optically-stimulated luminescence. The 4.77 eV OA trap is populated by electrons liberated during irradiation and its experimental OA relative efficiency was successfully predicted using a target size of 9 nm in the simulations. On the other hand, the model was not able to reproduce the values of the experimentally-observed proton induced OA efficiency above unity for the 5.08 eV OA band associated with the F centers in LiF:Mg,Ti (electron occupied Fluoride vacancy). The F centers are initially present in the LiF lattice but are also created by the irradiation. Since the absence of defect creation by the irradiation is a necessary condition of the microdosimetric model, the discrepancy between the model results for the F band and the experimental data was not unexpected. The calculations for both OA bands are presented as a function of the particle energy and the simulated microdosimetric target size and will be useful in further applications of the model OA relative efficiencies for charged particles. • The relative OA efficiency of LiF:Mg,Ti detectors was calculated for two OA bands. • 4.77 eV OA band: the model agrees with the experimental data for a 9 nm target. • 5.08 eV OA band: as expected, the model cannot reproduce the experimental data. [ABSTRACT FROM AUTHOR]

The proton depth dose profile measured by luminescent detectors differs from the one measured with reference dosimeters (i.e. ionization chambers) because of several effects including efficiency quenching and changes in the attenuation of the emitted light in case of partial detector irradiation. Using the Microdosimetric d(z) Model in combination with the Monte Carlo radiation transport code PHITS, a methodology was developed to tackle all these factors and calculate the response of luminescent when exposed at different positions along a proton Bragg peak. The results were compared against experimental data gathered with 7LiF:Mg,Ti (MTS-7) and 7LiF:Mg,Cu,P (MCP-7) thermoluminescent detectors, showing a very good agreement (average relative deviation ~ 3% for both detector types, smaller than the combined experimental uncertainty). • The Microdosimetric d(z) Model was coupled with nanoscale simulations using PHITS. • The response of luminescent detectors was predicted along a clinical proton Bragg peak. • A very good agreement with experimental data was found. • The Microdosimetric d(z) Model can be reliably used for calculations in mixed fields. [ABSTRACT FROM AUTHOR]

7LiF:Mg,Cu,P (MCP-7) thermoluminescent detectors were exposed at nine positions within a 60 MeV pristine proton Bragg peak to investigate the possibility of counteracting the occurrence of their low temperature anomalous behavior (strong increase in the relative intensity of the peak 3 after exposure to energetic charged particles, Parisi et al., 2018 a) by using the post-irradiation pre-readout thermal protocol of 120 °C for 30 min. Simulations with the Monte Carlo radiation transport code PHITS were performed in order to determine the absorbed dose, the LET and the specific energy density distributions within the detector volume as a function of its position along the Bragg peak. The experimentally determined efficiency values for the main peak signal agreed with the results of the Microdosimetric d(z) Model with an average deviation of 2.4%. The consistency of the results supports the hypothesis that the light signal of the main peak 4 partly arises from trapped charge carriers previously giving rise to the neighboring low-temperature peak 3 and that the non-standardized post-irradiation procedure is the reason for the spread in the experimentally determined proton efficiency data present in literature. Thus, for a correct dose assessment and to mitigate possible low temperature anomalies in the glow curve structure of LiF:Mg,Cu,P detectors, it is strongly advised to always employ the recommended preheat protocol of 30 min at 120 °C. • Using an optimal pre-heat protocol, LiF:Mg,Cu,P efficiency to protons was determined. • A very good agreement with theoretical efficiency values was found. • The low temperature anomalous behavior was successfully counteracted. • The phenomenon was explained as charge carrier migration from peak 3 to peak 4. [ABSTRACT FROM AUTHOR]

Abstract: Several properties of the response of thermoluminescence detectors after doses of ionising radiation can be explained by analysing the structure of charged particle tracks. Information on the topology of interaction points around the path of a charged particle can be represented through the radial distribution of average dose around the particle''s path (Track Structure) or through quantities such as lineal energy, , or specific energy, , applied in Microdosimetry. A principal assumption in all microdosimetric and track structure models is that, on a per average dose basis, the local efficiency of the TL processes taking place in any small volume located in the non-uniformly distributed dose distribution around the particle''s path is similar to that after irradiation with a uniformly distributed dose of -rays. Since saturation of -ray response at high doses then translates to saturation of this response over regions of high dose close to the path of the heavy charged particle, track structure theory and microdosimetric models are able to explain the decrease of TL efficiency after irradiation by heavy charged particles, and the anomalously low photon energy response of LiF:Mg,Cu,P after doses of X-rays. The enhanced photon energy response and enhanced response after heavy charged particle irradiation of LiF:Mg,Ti are connected with the supralinearity of this detector at higher doses of gamma-rays: if this response is sublinear (prior to saturation) the measured photon energy response is lower, and if it is supralinear—it is higher than that expected from the calculation of the interaction cross sections alone. The explanation of the correlation between dose-, energy- and LET-responses of TLDs is perhaps the most important contribution of microdosimetry to solid state dosimetry. [Copyright &y& Elsevier]

This review explores current experimental methods for determining the radiation quality in ion beams. In this context, radiation quality is commonly evaluated using the averaged linear energy transfer (LET), a metric employed to assess the response of both biological and physical systems. Dose and averaged LET can be experimentally determined with passive detectors through various techniques that have seen recent improvements. Another metric related to the LET is the mean lineal energy, which is measurable using microdosimetric detectors. This review focuses on the available possibilities for evaluating the radiation quality using three microdosimeters (mini-TEPC, Silicon Telescope, and SOI Microplus), three passive luminescence detectors (based on optical, thermo-, and radiophoto-luminescence), three track-based detectors (track-etched detector, Timepix, fluorescent nuclear track detector), and a chemical detector based on alanine. A comparison of detector properties is provided along with an overview of the underlying mechanisms enabling LET assessment or measurements of the mean lineal energy with each detector type. Finally, this review summarizes the current possibilities of LET determination with respect to the needs for quality assurance in particle therapy. Areas for future research and development are suggested. • Review of experimental radiation quality assessment via LET or yD. • Understand operating principles of passive and active LET detectors. • Tables summarize detector properties for LET or yD assessment. • Gain recommendations for LET-QA in particle therapy. [ABSTRACT FROM AUTHOR]

Abstract: Dosimetry of the monoenergetic raster-scanned beam of 12C carbon ions at GSI Darmstadt was performed using the LiF:Mg,Cu,P (MCP-N) 2-D thermoluminescence (TL) system. Several of TL foils of sizes and one were exposed to carbon ion beams of energies ranging between 88 and 430MeV/amu at doses ranging between 5 and 25Gy. The measured TL efficiency of the TL foil detectors, relative to 60Co -rays, varies between 0.30 at 88MeV/amu and 0.47 at 430MeV/amu and is well described by the microdosimetric One Hit Detector Model. In the investigated dose range the 2-D TLD system shows a linear dose response. Despite their appreciable energy response the 2-D TL foils based on LiF:Mg,Cu,P can be a useful tool for quality assurance of raster-scanned carbon ion beams. [Copyright &y& Elsevier]

Purpose: To identify differential cellular responses after proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type.Methods and Materials: A panel of primary dermal fibroblast cultures was irradiated with low and higher linear energy transfer (LET) proton beams. Cobalt-60 photon irradiation was used as reference. Dose was delivered in 3 fractions of 3.5 Gy (relative biological effectiveness) using a relative biological effectiveness of 1.1 for proton doses. Cells were harvested 2 hours after the final fraction was delivered, and RNA was purified. RNA sequencing was performed using Illumina NextSeq 500 with high-output kit. The edgeR package in R was used for differential gene expression analysis.Results: Pairwise comparisons of the transcriptomes in the 3 treatment groups showed that there were 84 and 56 differentially expressed genes in the low LET group compared with the Cobalt-60 group and the higher LET group, respectively. The higher LET proton group and the Cobalt-60 group had the most distinct transcriptome profiles, with 725 differentially regulated genes. Differentially regulated canonical pathways and various regulatory factors involved in regulation of biological mechanisms such as inflammation, carcinogenesis, and cell cycle control were identified.Conclusions: Inflammatory regulators associated with the development of normal tissue complications and malignant transformation factors seem to be differentially regulated by higher LET proton and Cobalt-60 photon irradiation. The reported transcriptome differences could therefore influence the progression of adverse effects and the risk of developing secondary cancers. [ABSTRACT FROM AUTHOR]

Lithium fluoride (LiF) thermoluminescent detectors (TLDs) are commonly used for measurements in mixed high energy radiation fields such as space, hadron radiotherapy and other high energy accelerator facilities. However, the results of these measurements are often challenging to interpret since the radiation field compositions are not known a priori. The goal of this work was to model and understand the LiF TLD response in the CERN-EU high-energy Reference Field (CERF). Six different LiF TLD types, namely MTS (LiF:Mg,Ti) and MCP (LiF:Mg,Cu,P) TLDs with different Li abundances, were irradiated at CERF. For the modelling of their response, CERF reference fluence energy spectra from FLUKA simulations and TLD relative luminescence efficiencies according to the Microdosimetric d(z) Model were collected from previous works and supplemented with new relative luminescence efficiency calculations for neutrons with energies above 0.01 MeV. Dedicated MCNP6.2 simulations were performed to obtain the required fluence to absorbed dose conversion factors. Results demonstrated that the response of LiF detectors can be well predicted even for complicated, mixed radiation fields. The modelling allowed to assess the dose contributions from different radiation types in mixed fields. Based on the results of this work, a methodology was proposed to perform LiF TLD measurements in well-characterized mixed fields in terms of absorbed dose in water or tissue. In unknown mixed radiation fields MTS-7 TLDs are recommended to assess the non-neutron component of the absorbed dose in water or tissue. Assessing the dose from neutrons requires dedicated neutron detectors. • Six different LiF TLD types were used for dose assessment at CERF. • The response of these TLDs and the contributions from different radiation types were modelled in detail. • Measured and modelled doses were in good agreement with each other. • Recommendations were given for LiF TLD measurements in mixed radiation fields such as hadron therapy and space. [ABSTRACT FROM AUTHOR]

This review of dosimetry for second cancer risk estimation introduces work carried out by Working Group 9 (WG9: Radiation Protection Dosimetry in Medicine) of the European Radiation Dosimetry Group (EURADOS). The work concentrates on the measurement of out-of-field doses in water phantoms using a variety of dosimeters to measure photon and neutron doses. These include optically stimulated luminescence (OSL), radiophotoluminescence (RPL) and thermoluminescence (TLD) dosimeters for photon dosimetry (together with ion chambers for reference measurements) and track etch and superheated emulsion detectors for neutron measurements. The motivation of WG 9 was to assess undue, non-target patient doses in radiotherapy and the related risks of second malignancy. Improvements in cancer treatment have increased survival times and thus increased incidence of second cancer may be expected in the future. In addition, increased whole body exposure may result from some developments in radiotherapy. This means that radiotherapy clinics will need to simulate their treatments in order to estimate and minimise doses to healthy tissues and organs. The proposed work is designed to generate a robust dataset of out-of-field dose measurements which can be used for the development and validation of dose algorithms. [ABSTRACT FROM AUTHOR]

Abstract: In this part of work carried out by Working Group 9 (Radiation Protection Dosimetry in Medicine) of the European Radiation Dosimetry Group (EURADOS), water tank experiments described in this issue (Bordy et al., 2013) were extended to a BOMAB-like phantom. This phantom is more clinically realistic than a water tank, sufficiently to allow the simulation of some clinical treatments. In the experiments to be described, four types of prostate treatment were simulated: Volumetric Modulated Arc Therapy (VMAT, 6 MV), Tomotherapy (6 MV), IMRT (6 MV and 18 MV), 5-field conformal radiotherapy (15 MV) and 4-field conformal radiotherapy (6 MV and 18 MV). Irradiations were performed in two centres, University Hospital of Santa Chiara, Pisa, Italy and Centre of Oncology M. Skłodowska-Curie Memorial Institute, Krakow, Poland. Whatever the difficulties and uncertainties in risk estimation, its foundation lies in the knowledge of the absorbed dose to the irradiated organs. Thus the measurement of out-of-field doses is a crucial pre-requisite for risk estimation and is the subject of the EURADOS Working Group 9. For photon out-of-field dose measurements TLD, OSL and RPL dosimeters were used. Comparison of dosimeters under the same irradiation conditions showed that dosimeters generally agreed to within 3% compared with ion chamber reference measurements. Other comparisons were possible with these data. They include a comparison of doses (beam profiles) in different positions in the BOMAB phantom, a comparison of different treatment modalities in the two contributing clinical centres (Pisa and Krakow) and a comparison of dose profiles resulting from the different treatment techniques and the corresponding doses calculated by the treatment planning systems used to generate the treatment plans. Finally, preliminary measurements of surface doses at selected points on the trunk of the BOMAB phantom were made using diode detectors. Comparison of out-of-field doses for different modalities in the two clinical centres shows that differences in out-of-field doses for the same Planning Treatment Volume (PTV) can be even a factor of 4. For sparing adjacent organs-at-risk the best results were obtained for IMRT. On the other hand the lowest out-of-field doses were for MLC conformal therapy. [Copyright &y& Elsevier]