Radiation measurements in the International Space Station, Columbus module, in 2020-2022 with the LIDAL detector.

The Light Ion Detector for ALTEA (LIDAL) is a new instrument designed to measure flux, energy spectra and Time of Flight of ions in a space habitat. It was installed in the International Space Station (Columbus) on January 19, 2020 and it is still operating. This paper presents the results of LIDAL measurements in the first 17 months of operation (01/2020-05/2022). Particle flux, dose rate, Time of Flight and spectra are presented and studied in the three ISS orthogonal directions and in the different geomagnetic regions (high latitude, low latitude, and South Atlantic Anomaly, SAA). The results are consistent with previous measurements. Dose rates range between 1.8 nGy/s and 2.4 nGy/s, flux between 0.21 particles/(sr cm2 s) and 0.32 particles/(sr cm2 s) as measured across time and directions during the full orbit. These data offer insights concerning the radiation measurements in the ISS and demonstrate the capabilities of LIDAL as a unique tool for the measurement of space radiation in space habitats, also providing novel information relevant to assess radiation risks for astronauts.

Microdosimetric analysis of the radiation quality of two different proton beams in the distal edge of the depth-dose profile.

Proton-therapy exploits the advantageous depth-dose profile of protons to induce the highest damage to tumoral cells in the last millimetres of their range in sharp Bragg Peak. To cover the whole tumoral volume, beams of different energies are combined to create the Spread Out Bragg Peak (SOBP). In passive modulated beams, the energy spread is created with modulators in which the highest energy beam is degraded through different thicknesses of calibrated plastic materials. The highest energy is chosen depending on the deepest point that needs to be treated. This study aims to investigate differences in the radiation quality in the distal edge of SOBP beams with different initial energy and modulation techniques based on microdosimetric measurements with mini Tissue-Equivalent Proportional Counters. The beams investigated are the 62 MeV proton SOBP of the clinical facility of CATANA and the 148 MeV proton SOBP of the research beam line of the proton-therapy centre of Trento.

FLUKA simulation of target fragmentation in proton therapy.

In proton therapy, secondary fragments are created in nuclear interactions of the beam with the target nuclei. The secondary fragments have low kinetic energies and high atomic numbers as compared to primary protons. Fragments have a high LET and deposit all their energy close to the generation point. For their characteristics, secondary fragments can alter the dose distribution and lead to an increase of RBE for the same delivered physical dose. Moreover, the radiobiological impact of target fragmentation is significant mostly in the region before the Bragg peak, where generally healthy tissues are present, and immediately after Bragg peak. Considering the high biological impact of those particles, especially in the case of healthy tissues or organs at risk, the inclusion of target fragmentation processes in the dose calculation of a treatment planning system can be relevant to improve the treatment accuracy and for this reason it is one of the major tasks of the MoVe IT project. In this study, Monte Carlo simulations were employed to fully characterize the mixed radiation field generated by target fragmentation in proton therapy. The dose averaged LET has been evaluated in case of a Spread Out Bragg Peak (SOBP). Starting from LET distribution, RBE has been evaluated with two different phenomenological models. In order to characterize the mixed radiation field, the production cross section has been evaluated by means of the FLUKA code. The future development of present work is to generate a MC database of fragments fluence to be included in TPS.

Beam characterization and feasibility study for a small animal irradiation platform at clinical proton therapy facilities.

A deeper understanding of biological mechanisms to promote more efficient treatment strategies in proton therapy demands advances in preclinical radiation research. However this is often limited by insufficient availability of adequate infrastructures for precision image guided small animal proton irradiation. The project SIRMIO aims at filling this gap by developing a portable image-guided research platform for small animal irradiation, to be used at clinical facilities and allowing for a precision similar to a clinical treatment, when scaled down to the small animal size. This work investigates the achievable dosimetric properties of different lowest energy clinical proton therapy beams, manipulated by a dedicated portable beamline including active focusing after initial beam energy degradation and collimation. By measuring the lateral beam size in air close to the beam nozzle exit and the laterally integrated depth dose in water, an analytical beam model based on the beam parameters of the clinical beam at the Rinecker Proton Therapy Center was created for the lowest available clinical beam energy. The same approach was then applied to estimate the lowest energy beam model of different proton therapy facilities, Paul Scherrer Institute, Centre Antoine Lacassagne, Trento Proton Therapy Centre and the Danish Centre for Particle Therapy, based on their available beam commissioning data. This comparison indicated similar beam properties for all investigated sites, with emittance values of a few tens of mm·mrad. Finally, starting from these beam models, we simulated propagation through a novel beamline designed to manipulate the beam energy and size for precise small animal irradiation, and evaluated the resulting dosimetric properties in water. For all investigated initial clinical beams, similar dosimetric results suitable for small animal irradiation were found. This work supports the feasibility of the proposed SIRMIO beamline, promising suitable beam characteristics to allow for precise preclinical irradiation at clinical treatment facilities.

Microdosimetric measurements as a tool to assess potential in-field and out-of-field toxicity regions in proton therapy.

Relative biological effectiveness (RBE) variations are thought to be one of the primary causes of unexpected normal-tissue toxicities during tumor treatments with charged particles. Unlike carbon therapy, where treatment planning is optimized on the basis of the RBE-weighted dose, a constant RBE value of 1.1 is currently used in proton therapy. Assuming a uniform value can lead to under- or over-dosage, not just to the tumor but also to surrounding normal tissue. RBE changes have been linked with dose/fraction, the biological endpoint and beam properties. Understanding radiation quality and the associated RBE can improve the prediction of normal-tissue toxicities. In this study, we exploited microdosimetry for characterizing radiation quality in proton therapy in-field, and off-beam at 20 (beam edge), 50 (close out-of-field) and 100 (far out-of-field) mm from the beam center. We measured the lineal energy y spectra in a water phantom irradiated with 152 MeV protons, from which beam quality as well as the physical dose could be obtained. Taking advantage of the linear quadratic model and a modified version of the microdosimetric kinetic model, the microdosimetric data were combined with radiobiological parameters (α and ß) of human salivary gland tumor cells for assessing cell survival RBE and RBE-weighted dose. The results indicate that if a dose of 60 Gy is delivered to the peak, the beam edge receives up to 6 Gy while the close and far out-of-field regions receive doses on the order of 10-3 Gy and 10-4 Gy, respectively. The RBE estimate in-beam shows large variations, ranging from 1.0 ± 0.2 at the entrance channel to 2.51 ± 0.15 at the tail. The beam edge follows a similar trend but the RBE calculated at the Bragg peak depth is 2.27 ± 0.17, i.e. twice the RBE in-beam (1.05 ± 0.15). Out-of-field, the estimated RBE is always significantly higher than 1.1 and increases with increasing lateral distance, reaching the overall highest value of 3.4 ± 0.3 at a depth of 206 mm and a lateral distance of 10 mm. The combination of RBE and dose into the biological dose points to the beam edge and the end-of-range in-beam as the areas with the highest risk of potential toxicities.

Transversal dose profile reconstruction for clinical proton beams: A detectors inter-comparison.

PURPOSE: The main purpose of this work is the inter-comparison between different devices devoted to the transversal dose profile recostruction for daily QA tests in proton therapy. METHODS: The results obtained with the EBT3 radiochromic films, used as a reference, and other common quality control devices, have been compared with those obtained with a beam profiling system developed at the "Laboratori Nazionali del Sud" of Italian Institute for Nuclear Physics (INFN-LNS, Catania, Italy). It consists of a plastic scintillator screen (thickness 1 mm), mounted perpendicularly to the beam axis and coupled with a highly sensitive CCD detector in a light-tight box. RESULTS AND CONCLUSION: The tests, carried out both at the INFN-LNS and Trento Proton Therapy Center facilities, show, in general, a good agreement between the different detectors. The beam profiling system, in particular, appears to be a promising quality control device for 2-D relative dosimetry, because of its linear response in a dose rate range useful for proton therapy treatments, its high spatial resolution and its short acquisition and processing time.

Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review.

Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28  months (range, 6-90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3-4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

STUDY FOR A PASSIVE SCATTERING LINE DEDICATED TO RADIOBIOLOGY EXPERIMENTS AT THE TRENTO PROTON THERAPY CENTER.

The recent worldwide spread of Proton Therapy centers paves the way to new opportunities for basic and applied research related to the use of accelerated proton beams. Clinical centers make use of proton beam energies up to about 230 MeV. This represents an interesting energy range for a large spectrum of applications, including detector testing, radiation shielding and space research. Additionally, radiobiology research might benefit for a larger availability of proton beams, especially in those centers where a room dedicated to research activities also exists. Here, we describe the initial activities for the setup of a radiobiology irradiation facility at the Trento Proton Therapy Center. Data referring to the characterization of the beam in air are essential to that purpose and will be presented. A basic setup for large field irradiation will be also proposed, which is needed for the majority of in vitro and in vivo radiobiology experiments.

Application of the local effect model to predict DNA double-strand break rejoining after photon and high-LET irradiation.

In the recent version of the local effect model (LEM), the biological effects of ionising radiation can be well described trough the consideration of DNA double-strand breaks (DSB) clustering at the micrometre scale. Assuming a giant-loop organisation for the chromatin higher-order structure, two classes of DSB are defined, namely isolated (iDSB) and clustered DSB (cDSB), according to whether exactly one or more than one DSB are induced in a loop, respectively. Here, a DSB kinetic rejoining model based on the LEM is applied to the description of two specific aspects of DSB rejoining, namely the dose dependence of the rejoining capacity after photon radiation and the residual damage observed at late times after ion irradiation. Based on the hypothesis that iDSB and cDSB can be associated to the fast and slow components of rejoining, the model is able to reproduce the experimental data, therefore supporting the relevance of micrometre scale clustering of damage for photon radiation as well as for high-LET radiation.

A DNA double-strand break kinetic rejoining model based on the local effect model.

We report here on a DNA double-strand break (DSB) kinetic rejoining model applicable to a wide range of radiation qualities based on the DNA damage pattern predicted by the local effect model (LEM). In the LEM this pattern is derived from the SSB and DSB yields after photon irradiation in combination with an amorphous track structure approach. Together with the assumption of a giant-loop organization to describe the higher order chromatin structure this allows the definition of two different classes of DSB. These classes are defined by the level of clustering on a micrometer scale, i.e., "isolated DSB" (iDSB) are characterized by a single DSB in a giant loop and "clustered DSB" (cDSB) by two or more DSB in a loop. Clustered DSB are assumed to represent a more difficult challenge for the cell repair machinery compared to isolated DSB, and we thus hypothesize here that the fraction of isolated DSB can be identified with the fast component of rejoining, whereas clustered DSB are identified with the slow component of rejoining. The resulting predicted bi-exponential decay functions nicely reproduce the experimental curves of DSB rejoining over time obtained by means of gel electrophoresis elution techniques as reported by different labs, involving different cell types and a wide spectrum of radiation qualities. New experimental data are also presented aimed at investigating the effects of the same ion species accelerated at different energies. The results presented here further support the relevance of the proposed two classes of DSB as a basis for understanding cell response to ion irradiation. Importantly the density of DSB within DNA giant loops of around 2 Mbp size, i.e., on a micrometer scale, is identified as a key parameter for the description of radiation effectiveness.