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Using microdosimetry, we investigated the relative biological effectiveness (RBE) and quality factor (Q¯) variations in- and out-of-field as a function of radiation quality for clinical protons.we irradiated a water phantom with a Spread-Out-Bragg-Peak (SOBP) and acquired microdosimetric spectra at several distal and lateral depths with a Tissue Equivalent Proportional Counter. The measurements were used as inputs to the Microdosimetric Kinetic and Loncol models to determine the RBE spatial distribution and compared it to predictions from the LETThe data demonstrate that radiation quality changes more rapidly with depth than lateral distance from the SOBP. In-beam, yFurther investigation will be necessary to evaluate the quantitative impact of RBE variations on the treatment planning and assess the clinical consequences both in terms of tumor control and normal tissue toxicity. The achievement of this goal calls for accurate radiobiological data to validate the RBE models.

Carbon therapy is a promising treatment option for cancer. The physical and biological properties of carbon ions can theoretically allow for the delivery of curative doses to the tumor, while simultaneously limiting risks of toxicity to adjacent healthy structures. The treatment effectiveness can be further improved by decreasing the uncertainties stemming from several sources, including the modeling of tissue heterogeneity. Current treatment plans employ density-based conversion methods to translate patient-specific anatomy into a water system, where dose distribution is calculated. This approach neglects differences in nuclear interactions stemming from the elemental composition of each tissue. In this work, we investigated the interaction of therapeutic carbon ions with bone-like materials. The study concentrated on nuclear interactions and included attenuation curves of 200 and 400 AMeV beams in different types of bones, as well as kinetic energy spectra of all charged fragments produced up to 29 degrees from the beam direction. The comparison between measurements and calculations of the treatment planning system TRiP98 indicated that bone tissue causes less fragmentation of carbon ions than water. Overall, hydrogen and helium particles were found to be the most abundant species, while heavier fragments were mostly detected within 5 degrees from the beam direction. We also investigated how the presence of a soft tissue-bone interface could affect the depth-dose profile. The results revealed a dose spike in the transition region, that extended from the entry channel to the target volume. The findings of this work indicated that the tissue-to-water conversion method based only on density considerations can result in dose inaccuracies. Tissue heterogeneity regions containing bones can potentially produce dose spikes, whose magnitude will depend on the patient anatomy. Dose uncertainties can be decreased by modeling nuclear interactions directly in bones, without applying the tissue-to-water conversion.

The present work introduces a rigorous stochastic model, called the generalized stochastic microdosimetric model (GSM^{2}), to describe biological damage induced by ionizing radiation. Starting from the microdosimetric spectra of energy deposition in tissue, we derive a master equation describing the time evolution of the probability density function of lethal and potentially lethal DNA damage induced by a given radiation to a cell nucleus. The resulting probability distribution is not required to satisfy any a priori conditions. After the initial assumption of instantaneous irradiation, we generalized the master equation to consider damage induced by a continuous dose delivery. In addition, spatial features and damage movement inside the nucleus have been taken into account. In doing so, we provide a general mathematical setting to fully describe the spatiotemporal damage formation and evolution in a cell nucleus. Finally, we provide numerical solutions of the master equation exploiting Monte Carlo simulations to validate the accuracy of GSM^{2}. Development of GSM^{2} can lead to improved modeling of radiation damage to both tumor and normal tissues, and thereby impact treatment regimens for better tumor control and reduced normal tissue toxicities.

Charged Particle Therapy (CPT) is a powerful radiotherapy technique for the treatment of deep-seated tumours characterized by a large dose released in the Bragg peak area (corresponding to the tumour region) and a small dose delivered to the surrounding healthy tissues. The precise measurement of the fragments produced in the nuclear interactions of charged particle beams with patient tissues is a crucial task to improve the clinical treatment plans. The FOOT (FragmentatiOn Of Target) experiment is an international project, funded by the Istituto Nazionale di Fisica Nucleare (INFN), aimed to study the dose released by the tissues and particle beams fragmentation. The target (16O, 12C) fragmentation induced by 150-400 MeV/n proton beams will be studied via the inverse kinematic approach, where 16O and 12C therapeutic beams collide on graphite and hydrocarbon target to provide the cross section on Hydrogen. A table-top detector is being developed and it includes a drift chamber as a beam monitor upstream of the target to measure the beam direction, a magnetic spectrometer based on silicon pixel and strip detectors, a scintillating crystal calorimeter able to stop the heavier produced fragments, and a ΔE detector, with TOF capability, for the particle identification. A setup based on the concept of the “Emulsion Cloud Chamber”, coupled with the interaction region of the electronic FOOT setup, will complement the physics program by measuring lighter charged fragments to extend the angular acceptance up to about 70 degrees. In this work, the experimental design and the requirements of the FOOT experiment will be discussed and preliminary results on the emulsion spectrometer tests will be presented.

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 β) 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.

In a carbon ion treatment the nuclear fragmentationof both target and beam projectiles impacts on the dose releasedon the tumor and on the surrounding healthy tissues. Carbon ionfragmentation occurring inside the patient body has to be stud-ied in order to take into account this contribution. These dataare also important for the development of the range monitoringtechniques with charged particles. The production of chargedfragments generated by carbon ion beams of 115-353 MeV/ukinetic energy impinging on carbon, oxygen, and hydrogen tar-gets has been measured at the CNAO particle therapy center(Pavia, Italy). The use of thin targets of graphite (C), PMMA(C2O5H8) and polyvinyl-toluene [plastic scintillator (PS), CbHa]allowed to measure fragments production cross sections, exploit-ing a time-of-flight (ToF) technique. PS detectors have been usedto perform the ToF measurements, while LYSO crystals havebeen used for the deposited energy measurement and to performparticle identification. Cross sections have been measured at 90◦and 60◦with respect to the beam direction. The measured pro-ton, deuteron, and triton differential production cross sectionson C, O, and H, obtained exploiting the target subtraction strat-egy, are presented here as a function of the fragment kineticenergy.

Carbon therapy is a promising treatment option for cancer. The physical and biological properties of carbon ions can theoretically allow for the delivery of curative doses to the tumor, while simultaneously limiting risks of toxicity to adjacent healthy structures. The treatment effectiveness can be further improved by decreasing the uncertainties stemming from several sources, including the modeling of tissue heterogeneity. Current treatment plans employ density-based conversion methods to translate patient-specific anatomy into a water system, where dose distribution is calculated. This approach neglects differences in nuclear interactions stemming from the elemental composition of each tissue. In this work, we investigated the interaction of therapeutic carbon ions with bone-like materials. The study concentrated on nuclear interactions and included attenuation curves of 200 and 400 AMeV beams in different types of bones, as well as kinetic energy spectra of all charged fragments produced up to 29 degrees from the beam direction. The comparison between measurements and calculations of the treatment planning system TRiP98 indicated that bone tissue causes less fragmentation of carbon ions than water. Overall, hydrogen and helium particles were found to be the most abundant species, while heavier fragments were mostly detected within 5 degrees from the beam direction. We also investigated how the presence of a soft tissue-bone interface could affect the depth-dose profile. The results revealed a dose spike in the transition region, that extended from the entry channel to the target volume. The findings of this work indicated that the tissue-to-water conversion method based only on density considerations can result in dose inaccuracies. Tissue heterogeneity regions containing bones can potentially produce dose spikes, whose magnitude will depend on the patient anatomy. Dose uncertainties can be decreased by modeling nuclear interactions directly in bones, without applying the tissue-to-water conversion.

Summary: Charged particle therapy exploits proton or 12C beams to treat deep-seated solid tumors. Due to the advantageous characteristics of charged particles energy deposition in matter, the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However, the beam nuclear interactions with the patient tissues induces fragmentation both of projectile and target nuclei and needs to be carefully taken into account. In proton treatments, target fragmentation produces low energy, short range fragments along all the beam range, which deposit a non negligible dose in the entry channel. In 12C treatments the main concern is represented by long range fragments due to beam fragmentation that release their dose in the healthy tissues beyond the tumor. The FOOT experiment (FragmentatiOn Of Target) of INFN is designed to study these processes, in order to improve the nuclear fragmentation description in next generation Treatment Planning Systems and the treatment plans quality. Target (16O and 12C nuclei) fragmentation induced by –proton beams at therapeutic energies will be studied via an inverse kinematic approach, where 16O and 12C therapeutic beams impinge on graphite and hydrocarbon targets to provide the nuclear fragmentation cross section on hydrogen. Projectile fragmentation of 16O and 12C beams will be explored as well. The FOOT detector includes a magnetic spectrometer for the fragments momentum measurement, a plastic scintillator for ΔE and time of flight measurements and a crystal calorimeter to measure the fragments kinetic energy. These measurements will be combined in order to make an accurate fragment charge and isotopic identification. Keywords: Hadrontherapy, Nuclear fragmentation cross sections, Tracking detectors, Scintillating detectors

In hadron therapy, the accelerated ions, interacting with the body of the patient, cause the fragmentation of both projectile and target nuclei. The fragments interact with the human tissues depositing energy both in the entrance channel and in the volume surrounding the tumor. The knowledge of the fragments features is crucial to determine the energy amount deposited in the human body, and - hence - the damage to the organs and to the tissues around the tumor target. The FOOT (FragmentatiOn Of Target) experiment aims at studying the fragmentation induced by the interaction of a proton beam (150-250 MeV/n) inside the human body. The FOOT detector includes an electronic setup for the identification of Z ≥ 3 fragments integrated with an emulsion spectrometer to measure Z ≤ 3 fragments. Charge identification by nuclear emulsions is based on the development of techniques of controlled fading of the particle tracks inside the nuclear emulsion, that extend the dynamical range of the films developed for the tracking of minimum ionising particles. The controlled fading strongly depends on temperature, relative humidity and treatment duration. In this study the performances in terms of charge separation of proton, helium and carbon particles, obtained on a batch of new emulsion films produced in Japan are reported.

LIDAL–ALTEA is a detector designed to study the radiation flux and energy spectra in the International Space Station (ISS). Its mission is manifested by NASA in 2019. The ALTEA subsystem, which took data on the ISS in the past Zaconte et al. (2010), is based on Silicon Strip detectors and will measure the released energy of the traversing particles, while the LIDAL subdetector is based on fast plastic scintillators , read by PMTs, will measure the particle Time Of Flight. A custom Front End electronics has been designed to reach a time resolution better than 120 ps. LIDAL is under construction while a prototype has been already tested with a proton beam . The measured time resolution fulfills the design expectation and is compatible with FLUKA simulations. The Monte Carlo results have also been validated by the comparison with a test measure where the ALTEA detector was exposed to proton beams.

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.

LIDAL (Light Ion Detector for ALTEA system) is a compact detector designed to upgrade ALTEA (Anomalous Long Term Effects on Astronauts) silicon detector apparatus, in order to study in detail the low-Z part of ions spectrum inside the International Space Station (ISS) and to enhance the Particle Identification (PID) capability of the system. The new detector is designed to trigger ALTEA and to perform Time-Of-Flight measurements. It is based on plastic scintillators for fast timing applications read by Photo-Multiplier-Tubes (PMTs). A custom Front End Electronics (FEE) has been designed to reach time resolutions less than 100 ps ( σ ) for protons. A LIDAL prototype has been developed at the University of Rome Tor Vergata to test the timing performance of the scintillators, the PMTs and of the custom FEE using the proton beam line at the TIFPA (Trento Institute for Fundamentals Physics Applications) center in Trento, Italy. The results of these tests are reported and discussed. They have also been used for a preliminary evaluation of the Particle Identification (PID) capability of the final LIDAL-ALTEA detector system in response to the ions spectra expected on-board the ISS.

International audience; Prompt-gamma emission detection is a promising technique for hadrontherapy monitoring purposes. In this regard, obtaining prompt-gamma yields that can be used to develop monitoring systems based on this principle is of utmost importance since any camera design must cope with the available signal. Herein, a comprehensive study of the data from ten single-slit experiments is presented, five consisting in the irradiation of either PMMA or water targets with lower and higher energy carbon ions, and another five experiments using PMMA targets and proton beams. Analysis techniques such as background subtraction methods, geometrical normalization, and systematic uncertainty estimation were applied to the data in order to obtain absolute prompt-gamma yields in units of prompt-gamma counts per incident ion, unit of field of view, and unit of solid angle. At the entrance of a PMMA target, where the contribution of secondary nuclear reactions is negligible, prompt-gamma counts per incident ion, per millimetre and per steradian equal to (124 ± 0.7stat ± 30sys) × 10−6 for 95 MeV u−1 carbon ions, (79 ± 2stat ± 23sys) × 10−6 for 310 MeV u−1 carbon ions, and (16 ± 0.07stat ± 1sys) × 10−6 for 160 MeV protons were found for prompt gammas with energies higher than 1 MeV. This shows a factor 5 between the yields of two different ions species with the same range in water (160 MeV protons and 310 MeV u−1 carbon ions). The target composition was also found to influence the prompt-gamma yield since, for 300/310 MeV u−1 carbon ions, a 42% greater yield ((112 ± 1stat ± 22sys) × 10−6 counts ion−1 mm−1 sr−1) was obtained with a water target compared to a PMMA one.

Purpose: Within the European project ALLEGRO (grant agreement no. 231965), the out‐of‐field dose delivered to a patient when treated with different radiotherapy modalities was investigated. The study compared the dose distribution during photon and particle irradiations both in a water and an anthropomorphic phantom to evaluate the risk of inducing secondary malignancies.Methods: Two sets of experiments with standardized conditions were used for a systematic comparison. In the former, a water phantom was irradiated with a 2D squared field to characterize the lateral dose fall‐off with high spatial resolution. The latter employed an anthropomorphic phantom treated for a target volume placed at the center of its head to simulate a braintumor. The dose was measured in several planes along the phantom main axis. For both types of experiments the dose was measured with a PTW diamond detector. Additionally, the use of TLDs and bubble detectors provided some information on the secondary neutron field produced both in the accelerator structure and the target itself. In total, experiments were conducted at six facilities using photons, protons and carbon ions; the ion irradiations were performed with passive delivery and the scanning technique. Results: A significant difference among the out‐of‐field dose profiles is observed for distances larger than 3 cm to the target. The distribution delivered by photons is a factor 10 to 400 higher than the values of charged particles. Scanning ions reduces the out‐of‐field dose more than passive delivery at distances larger than 10 cm. Conclusions: The study emphasizes the physical advantage of using charged particles for tumor therapy. Together with the favorable depth dose deposition, ions spare the normal tissue surrounding the target more efficiently than photons. These results imply a lower risk of long‐term effects, such as the induction of secondary malignancies, following treatments with particles compared to photons. This work was funded by the European ALLEGRO project (Grant Agreement No. 231965)

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Recently, the use of 4He particles in cancer radiotherapy has been reconsidered as they potentially represent a good compromise between protons and 12C ions. The first step to achieve this goal is the development of a dedicated treatment planning system, for which basic physics information such as the characterization of the beam lateral scattering and fragmentation cross sections are required. In the present work, the attenuation of 4He primary particles and the build-up of secondary charged fragments at various depths in water and polymethyl methacrylate were investigated experimentally for 120 and 200 MeV u-1 beams delivered by the synchrotron at the Heidelberg Ion-Beam Therapy Center, Heidelberg. Species and isotope identification was accomplished combining energy loss and time-of-flight measurements. Differential yields and energy spectra of all fragments types were recorded between 0° and 20° with respect to the primary beam direction.

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106–109 particles/s down to 101–105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.

The radiation used in hadrontherapy treatments interacts with the patient body producing secondary particles, either neutral or charged, that can be used for dose and Bragg peak monitoring and to provide a fast feedback on the treatment plans. Recent results obtained from the authors on simplified setups (mono-energetic primary beams interacting with homogeneous tissue-like target) have already indicated the correlation that exists between the flux of these secondaries coming from the target (e.g. protons and photons) and the position of the primary beam Bragg peak. In this paper, the measurements of charged particle fluxes produced by the interaction of a 220 MeV/u carbon ion beam at GSI, Darmstadt, with a polymethyl methacrylate target are reported. The emission region of protons (p), deuterons (d) and tritons (t) has been characterized using a drift chamber while the particle time-of-flight, used to compute the kinetic energy spectra, was measured with a LYSO scintillator. The energy released in the LYSO crystal was used for particle identification purposes. The measurements were repeated with the setup at 60° and 90° with respect to the primary beam direction. The accuracy on the fragments emission profile reconstruction and its relationship with the Bragg peak position have been studied. Based on the acquired experimental evidence, a method to monitor the dose profile and the position of the Bragg peak inside the target is proposed. © 2014 Institute of Physics and Engineering in Medicine.

The LIDAL (Light Ion Detector for ALTEA) is a device designed to work paired with three silicon detector units of ALTEA (Anomalous Long Term Effects on Astronauts) in order to improve the particle identification capabilities of ALTEA on the International Space Station also providing Time-of-Flight measurements. The LIDAL-ALTEA goal is to measure ions from protons up to iron in real time. The improved measurements of the radiation environment inside ISS will be very valuable for radiation risk assessment and mitigation. It is necessary to have a detailed simulation of the apparatus response to cosmic ray nuclei in order to assess the detector response, its observational capabilities and to set the relevant parameters of the device. Here a new Monte Carlo simulation of the LIDAL-ALTEA setup and physics processes, in the framework of FLUKA, is presented. A comparison between Monte Carlo simulations and calibration data is also shown.

La sicurezza del paziente sottoposto a trattamenti terapeutici con radiazioni ionizzanti e il buon esito degli ultimi sono strettamente legati all’ottimizzazione delle procedure di esposizione alle radiazioni ionizzanti. In particolare è fondamentale arrecare il danno minore possibile ai tessuti sani che circondano la neoplasia da trattare. Rispetto ai campi di radiazione convenzionali utilizzati in radioterapia (fotoni), le particelle cariche pesanti (protoni e ioni carbonio) offrono diversi vantaggi quali la bassa dispersione laterale, l’alta efficacia biologica (RBE) nella regione del picco di Bragg ed un profilo di dose caratteristico in profondità del tutto differente da quello dei fotoni. Queste caratteristiche rendono particolarmente vantaggioso l’uso di queste particelle per il trattamento di tumori radio-resistenti localizzati vicino agli organi a rischio. Tra i rivelatori a stato solido usati in ambito dosimetrico, trovano largo utilizzo i dosimetri a Risonanza Elettronica di Spin (ESR) a base di alanina per le loro caratteristiche dosimetriche quali la tessuto-equivalenza per fotoni, la linearità di risposta alla dose in un ampio range, l’alta stabilità nel tempo del segnale radioindotto, la non distruttività della procedura di lettura, l’indipendenza dal dose-rate; inoltre non è richiesto alcun trattamento del campione prima della misura ESR e i dosimetri hanno un costo decisamente basso. Queste peculiarità, associate alla possibilità di riconoscere le varie componenti di un campo misto di radiazioni, rendono l'alanina un buon candidato per effettuare stime di dose durante l’uso di fasci di protoni e ioni carbonio. L'obiettivo principale del presente lavoro è quello di studiare la risposta di pellets di alanina analizzati tramite ESR irradiati con fasci di ioni carbonio utilizzati in ambito clinico. Nello specifico, per gli ioni carbonio sono stati condotti studi dosimetrici in acqua ed in presenza di disomogeneità del mezzo (come all'interfaccia osso-acqua) per simulare uno scenario quasi-clinico. Gli esperimenti sono stati condotti presso il Dipartimento di Biofisica del GSI Helmholtzzentrum in Germania utilizzando un fascio modulato attivamente usato per il trattamento di tumori in profondità. I risultati sperimentali sono stati modellizzati e confrontati con I dati del treatment plannig system (TPS).

We report results for chromosomal aberrations in human peripheral blood lymphocytes after they were exposed to high-energy iron ions with or without shielding at the HIMAC, AGS and NSRL accelerators. Isolated lymphocytes were exposed to iron ions with energies between 200 and 5000 MeV/nucleon in the 0.1-1-Gy dose range. Shielding materials consisted of polyethylene, lucite (PMMA), carbon, aluminum and lead, with mass thickness ranging from 2 to 30 g/cm(2). After exposure, lymphocytes were stimulated to grow in vitro, and chromosomes were prematurely condensed using a phosphatase inhibitor (calyculin A). Aberrations were scored using FISH painting. The yield of total interchromosomal exchanges (including dicentrics, translocations and complex rearrangements) increased linearly with dose or fluence in the range studied. Shielding decreased the effectiveness per unit dose of iron ions. The highest RBE value was measured with the 1 GeV/nucleon iron-ion beam at NSRL. However, the RBE for the induction of aberrations apparently is not well correlated with the mean LET. When shielding thickness was increased, the frequency of aberrations per particle incident on the shield increased for the 500 MeV/nucleon ions and decreased for the 1 GeV/nucleon ions. Maximum variation at equal mass thickness was obtained with light materials (polyethylene, carbon or PMMA). Variations in the yield of chromosomal aberrations per iron particle incident on the shield follow variations in the dose per incident particle behind the shield but can be modified by the different RBE of the mixed radiation field produced by nuclear fragmentation. The results suggest that shielding design models should be benchmarked using both physics and biological data.

Introduction. Impaired wound healing represents a common operative complication after kidney transplantation. This problem seems to be affected by factors related to surgical technique, drugs, and patient/graft peculiarities. Patients and Methods. From January 2000 to December 2007, 350 consecutive kidney transplantations were performed in a population of nondiabetic patients. We evaluated the influence of various factors on impaired wound healing. Results. Among 350 kidney transplantation patients, we observed 54 cases (15.43%) of impaired healing of the surgical incision: 36 (10.29%) with first level and 18 (5.14%) with second level wound complications. Factors related to complications were overweight and delayed graft function. Cyclosporine and tacrolimus had similar effects. However, all patients developing second level complications showed more risk factors. In our experi- ence, postoperative lymphocele did not occur as an unique factor but became a significant risk factor when associated with another one. Patients who did not have reconstruction of the muscle layers showed a greater incidence of incisional complications. Conclusion. Impaired healing of the surgical incision more or less seriously influenced outcomes of transplanted patients. This complication was common and usually related to the presence of more than one risk factor.

Introduction In kidney transplantation, anatomical vascular and excretory anomalies may represent causes of failure. Today’s surgical techniques have made the most of the organs with anatomic anomalies and iatrogenic injury successfully used for transplantation. Materials and Methods From January 2000 to June 2006, we harvested 230 kidneys, of including 88 kidneys (20%) with vascular, urinary, or vascular-urinary anomalies; 64 kidneys were implanted and 15 were sent to other transplantation centers. Only 9 kidneys were not appropriate for transplantation. Results All patients who received kidneys with the above-mentioned anomalies were carefully examined after the transplantation and short-term and long-term complications were evaluated with respect to controls without anomalies. Discussion Renal anatomic anomalies are frequently observed during kidney transplantation and may produce postsurgical complications. However, the presence of these anomalies does not necessarily imply the impossibility of using the kidney for a transplant, especially because of improved surgical techniques. Our experience in transplantation procedures showed that even if kidneys present the above-mentioned anomalies they can still be considered appropriate for transplantation when we perform a correct harvesting/back-table transplant surgery. So vascular and urinary anomalies have to be considered always an incentive to research new surgical solutions and to perform a careful surgical technique.

In this work we presented a method to estimate a local shielding thickness of the International Space Station (USLab), expressed as equivalent of aluminum. The calculation took advantage of total and partial charge-changing cross sections, both measured experimentally and computed theoretically, to obtain the total survival fractions of ions with charge 5 ⩽ Z ⩽ 26 when transversing the space craft hull. The combination of these values with the measured relative abundances outside the space station provided the estimates of the internal relative abundances at several thicknesses. The results have been compared with data measured by ALTEA experiment in the USLab to find the thickness that minimizes the discrepancy between the calculated data and the measurements: the result yielded to an estimate of the shielding thickness at ALTEA site of about 5 cm of aluminum equivalent.

We present measurements and model calculations of fluence and linear energy transfer in water ( LET ∞ ) obtained using 56 Fe beams with 1 GeV/amu kinetic energy incident on aluminum, polyethylene, PMMA, and lead targets. The measured spectra are compared to predictions of the PHITS model. The study is motivated by NASA's need to develop accurate heavy ion transport codes to assess radiation exposures in deep space, where galactic cosmic rays are important. The data were obtained at the Alternating Gradient Synchrotron at the Brookhaven National Laboratory. Distributions of charge and LET depend on the depth and composition of the target. Several of the targets studied are “thick”, defined operationally as a depth that presents at least 50% of an interaction length to the beam ions. In a thick target, the probability of a secondary interaction is significant, tertiary interactions can also be important, and the target-exit fluence and charge distributions depend on unmeasured cross sections that can only be estimated by nuclear interaction models. Comparisons between calculated and measured spectra are therefore of considerable interest. Some targets used in the study are thin, so that secondary and higher interaction probabilities are negligible, allowing more stringent comparisons between the data and the model. We find that PHITS reproduces some aspects of the experimental data well, but fails to accurately reproduce many of the measured fragment fluences.

We have collected from the literature partial charge-changing cross sections for projectiles with charge 6

International audience; Longitudinal prompt-gamma ray profiles have been measured with a multi-slit multi-detector configuration at a 75 MeV/u 13C beam and with a PMMA target. Selections in time-of-flight and energy have been applied in order to discriminate prompt-gamma rays produced in the target from background events. The ion ranges which have been extracted from each individual detector module agree amongst each other and are consistent with theoretical expectations. In a separate dedicated experiment with 200 MeV/u 12C ions the fraction of inter-detector scattering has been determined to be on the 10%-level via a combination of experimental results and simulations. At the same experiment different collimator configurations have been tested and the shielding properties of tungsten and lead for prompt-gamma rays have been measured.

International audience; The radiation used in particle therapy treatments produces secondary particles, either neutral or charged, when interacting with the patient body. The particles that exit from the body can be used to provide a fast feedback on the treatment plans. Here we report the measurements of prompt-gamma ray fluxes produced by the interaction of a 220 MeV/u carbon ion beam at GSI, Darmstadt, with a polymethyl methacrylate (PMMA) target. The photons were detected by means of an array of LYSO crystals, allowing for a measurement of time of flight and released energy. Different angular configurations were explored, placing the prompt-gamma detector at 60 degrees, 90 degrees, and 120 degrees with respect to the primary beam direction. The prompt-gamma energy spectra have been obtained for the different angular configurations after having taken into account the detector resolution by means of an unfolding procedure tuned with a dedicated Monte Carlo simulation. The integrated fluxes (over the full 4 pi solid angle), in the 2-10 MeV prompt-gamma ray energy range, at 60 degrees, 0 degrees and 120 degrees, are measured as Phi(gamma) (60 degrees) = (6.7 +/- 1.7) x 10(-3) sr(-1), Phi(gamma) (90 degrees) = (6.3 +/- 2.1) x 10(-3) sr(-1) and Phi(gamma)(120 degrees) = (4.4 +/- 1.1) x 10(-3) sr(-1) respectively.

This investigation focused on the characterization of the lateral dose fall-off following the irradiation of the target with photons, protons and carbon ions. A water phantom was irradiated with a rectangular field using photons, passively delivered protons as well as scanned protons and carbon ions. The lateral dose profile in the depth of the maximum dose was measured using an ion chamber, a diamond detector and thermoluminescence detectors TLD-600 and TLD-700. The yield of thermal neutrons was estimated for all radiation types while their complete spectrum was measured with bubble detectors during the irradiation with photons. The peripheral dose delivered by photons is significantly higher compared to both protons and carbon ions and exceeds the latter by up to two orders of magnitude at distances greater than 50 mm from the field. The comparison of passive and active delivery techniques for protons shows that, for the chosen rectangular target shape, the former has a sharper penumbra whereas the latter has a lower dose in the far-out-of-field region. When comparing scanning treatments, carbon ions present a sharper dose fall-off than protons close to the target but increasing peripheral dose with increasing incident energy. For photon irradiation, the contribution to the out-of-field dose of photoneutrons appears to be of the same order of magnitude as the scattered primary beam. Charged particles show a clear supremacy over x-rays in achieving a higher dose conformality around the target and in sparing the healthy tissue from unnecessary radiation exposure. The out-of-field dose for x-rays increases with increasing beam energy because of the production of biologically harmful neutrons.

Introduction This study aims to investigate possible risk factors for diverticulitis in kidney transplant recipients affected by colonic diverticulosis. Methods and Results We investigated 717 patients transplanted between 2000 and 2010. Diverticular disease was endoscopically diagnosed in 17 of 717 examined patients. Eight patients were diagnosed with autosomal dominant polycystic kidney disease (ADPKD); 9 of 17 patients underwent emergency surgery. We performed Hartmann's procedure on all patients, with a second stage performed at least 6 months later. Discussion Although the incidence of colonic diverticular perforation in kidney transplanted patients is similar to that observed in the general population, perforation in immunosuppressed patients is associated with a higher morbidity/mortality rate. In our study, the incidence of perforation is 1.25% (9 of 717), with almost half of the cases observed in patients with ADPKD (4 of 9). Such an observation is consistent with published data, in which patients with ADPKD are reported to more frequently develop colonic diverticulosis and its complications. One possible explanation might be related to a belated diagnosis of diverticulitis, which could initially simulate an inflammatory disease as a consequence of renal cysts. Also, steroids seem to be a predisposing factor for colonic perforation in these patients. Conclusions A timely surgery can significantly reduce mortality. In cases of elective surgery, mortality and morbidity are similar to those of immunocompetent patients; accordingly, this is the goal to be pursued. Early signs and symptoms are often masked by immunosuppressive therapy. In these patients, surgeons should always perform (1) abdominal computed tomography scanning and, in the presence of diverticulitis, reduce or withdraw immunosuppressive therapy; and (2) early surgery, with Hartmann's procedure being, in our opinion, the best choice. Before transplantation, elective surgery for colonic resection should be considered in patients with ADPKD or with a history of 1 or more episodes of acute diverticulitis who then regressed with medical therapy.

Short- and long-term side effects following the treatment of cancer with radiation are strongly related to the amount of dose deposited to the healthy tissue surrounding the tumor. The characterization of the radiation field outside the planned target volume is the first step for estimating health risks, such as developing a secondary radioinduced malignancy. In ion and high-energy photon treatments, the major contribution to the dose deposited in the far-out-of-field region is given by neutrons, which are produced by nuclear interaction of the primary radiation with the beam line components and the patient's body. Measurements of the secondary neutron field and its contribution to the absorbed dose and equivalent dose for different radiotherapy technologies are presented in this work. An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5 × 2 × 5 cm3 cancer volume located in the center of the head. The experiment was repeated with 25 MV IMRT (intensity modulated radiation therapy) photons and charged particles (protons and carbon ions) delivered with both passive modulation and spot scanning in different facilities. The measurements were performed with active (silicon-scintillation) and passive (bubble, thermoluminescence 6LiF:Mg, Ti (TLD-600) and 7LiF:Mg, Ti (TLD-700)) detectors to investigate the production of neutral particles both inside and outside the phantom. These techniques provided the whole energy spectrum (E 20 MeV) and corresponding absorbed dose and dose equivalent of photo neutrons produced by x-rays, the fluence of thermal neutrons for all irradiation types and the absorbed dose deposited by neutrons with 0.8 < E < 10 MeV during the treatment with scanned carbon ions. The highest yield of thermal neutrons is observed for photons and, among ions, for passively modulated beams. For the treatment with high-energy x-rays, the contribution of secondary neutrons to the dose equivalent is of the same order of magnitude as the primary radiation. In carbon therapy delivered with raster scanning, the absorbed dose deposited by neutrons in the energy region between 0.8 and 10 MeV is almost two orders of magnitude lower than charged fragments. We conclude that, within the energy range explored in this experimental work, the out-of-field dose from secondary neutrons is lowest for ions delivered by scanning, followed by passive modulation, and finally by high-energy IMRT photons. © 2014 Institute of Physics and Engineering in Medicine.

We present here the energy spectra relative to different geomagnetic regions as measured by the ALTEA (Anomalous Long Term Effects on Astronauts) detector in the International Space Station – USLab from August 2006 to July 2007. ALTEA is an active detector composed by six silicon telescopes and it is able to follow the dynamics of the radiation flux, with the capability to discriminate impinging nuclei from Boron to Molybdenum. We divided each orbit in three regions (polar, equatorial and South Atlantic Anomaly), according to the values of the geomagnetic coordinates, and show the relative energy spectra. Finally we calculated the relative nuclear abundances compared to the ones of the total data. As expected all nuclear species are similarly modulated by the geomagnetic cutoff.

International audience; Prompt secondary radiations such as gamma rays and protons can be used for ion-range monitoring during ion therapy either on an energy-slice basis or on a pencil-beam basis. We present a review of the ongoing activities in terms of detector developments, imaging, experimental and theoretical physics issues concerning the correlation between the physical dose and hadronic processes

The uneven shielding of the International Space Station from the vessel hull, racks and experiments produces a modulation of the internal radiation environment. A detailed knowledge of this environment, and therefore of the Station's shielding effectiveness, is mandatory for an accurate assessment of radiation risk. We present here the first 3D measurements of the Station's radiation environment, discriminating particle trajectories and LET, made possible using the detection capability of the ALTEA-space detector. We provide evidence for a strong (factor ≈ 3) anisotropy in the inner integral LET for high-LET particles (LET50 keV/µm) showing a minimum along the longitudinal station axis (most shielded) and a maximum normal to it. Integrating over all measured LETs, the anisotropy is strongly reduced, showing that unstopped light ions plus the fragments produced by heavier ions approximately maintain flux/LET isotropy. This suggests that, while changing the quality of radiation, the extra shielding along the station main axis is not producing a benefit in terms of total LET. These features should be taken into account (1) when measuring radiation with detectors that cannot distinguish the direction of the impinging radiation or that are unidirectional, (2) when planning radiation biology experiments on the ISS, and (3) when simulating the space radiation environment for experiments on the ground. A novel analysis technique that fully exploits the ability to retrieve the angular distribution of the radiation is also presented as well as the angular particle flux and LET characteristic of three geomagnetic zones measured during 2009 by the ALTEA-space detector. This technique is applied to the ALTEA-space detector, but a wider applicability to other detectors is suggested.

Purpose: The purpose of this study is to investigate and quantify several factors affecting biological effects of carbon ions such as cell type, dose, energy and position where the cells are irradiated along the pristine Bragg curve. Methods: Experiments to quantify clonogenic cell survival in three human lung cancer cell lines and a fibroblast cell line were performed at the NASA Space Radiation Laboratory, BNL, Upton, USA. A system of water or media-filled T25 flasks lined up along the beam axis was designed so that the cell-containing surfaces of the flasks were placed at specific depths along the Bragg curve. Gaf-chromic films were placed between the flasks to monitor the dose distribution in the sample as soon as the irradiation was finished. Additional studies were conducted at four selected depths along the Bragg curve to obtain full cell survival dose response curves for the four cell lines. Results: The percent depth dose of the beams was determined using an ionization chamber and showed that the physical Bragg peak is at 22.5 cm water depth. However, the clonogenic cell survival data indicated that the maximum cell killing occurred at 21.5 cm. Gaf-chromic films revealed some inhomogeneity in the dose distribution on the flasks near the peak, presumably due to lack of scattering from the sides of the flasks, which might account for the differences. Depending on the cell line and radiation dose, the maximum cell killing (i.e., the greatest RBE) is at the 21.5 (the peak) or 24 cm (distal fall off) depth. Conclusion: There is a difference in biological effect along the Bragg curve of a carbon ion beam, indicating an elevated RBE at or beyond the end of the range. Gaf-chromic films are proven to be effective in monitoring the 2D irradiation pattern to the flasks. Research supported by NIH/NCI through grant no. R21 CA182259.

We have measured charged nuclear fragments produced by 1 GeV/nucleon 56 Fe ions interacting with aluminium, polyethylene and lead. These materials are relevant for assessment of radiation risk for manned space flight. The data will be presented in a form suitable for comparison with models of nuclear fragmentation and transport, including linear energy transfer (LET) spectrum, fluence for iron and fragments, event-tack- and even t-dose-averaged LET, total dose and iron contribution to dose.

Methods We reviewed our series concerning 27 patients submitted to total colectomy for CRC between January 2000 and September 2010. Indications were: synchronous tumors, cancer in FAP, HNPCC, and emergency. We divided them into two groups according to their age: 11 (40.7%) 3 days) were compared in two groups.

Solar Particle Events (SPEs) are a major concern during prolonged space missions. During such events, a large amount of light ions, mostly protons and helium nuclei, are accelerated with enough energy to traverse the spacecraft hull and therefore represent a high hazard for the crews' health. The ALTEA particle telescope was collecting continuous data inside the USLab module of the International Space Station (ISS) during most of the December 2006 SPEs. The telescope is able to measure protons and helium respectively in the 42–45 MeV and 42–250 MeV/nucleon energy ranges, heavier ions up to relativistic molybdenum, and to discriminate nuclei for Z ≥ 5. First measurements of the charged radiation environment inside the USLab during a SPE are presented. The data averaged over the entire SPE week show an increase of the light ion rate (about a factor 1.5 in the energy range of the detector) when compared to quiet Sun conditions. The increase becomes much higher during the SPE climax (13 December) reaching a factor 10 (when averaged over three ISS orbits showing the highest activity). The extension of these results beyond the detector range is discussed. Conversely, the rates of ions with Z ≥ 5 are shown not to change significantly during the SPE week.

Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back ??s, produced in the positron annihilation from ??+ emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt ??s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50?300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented.

Particle therapy uses proton or 12C beams for the treatment of deep-seated solid tumors. Due to the features of energy deposition of charged particles a small amount of dose is released to the healthy tissue in the beam entrance region, while the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However nuclear interactions between beam and patient tissues induce fragmentation both of projectile and target and must be carefully taken into account. In 12C treatments the main concern are long range fragments due to projectile fragmentation that release dose in the healthy tissue after the tumor, while in proton treatment the target fragmentation produces low energy, short range fragments along all the beam range. The FOOT experiment (FragmentatiOn Of Target) is designed to study these processes. Target nuclei (16O,12C) fragmentation induced by 150-250 AMeV proton beam will be studied via inverse kinematic approach. 16O,12C therapeutic beams, with the quoted kinetic energy, collide on graphite and hydrocarbons target to provide the cross section on Hydrogen. This configuration explores also the projectile fragmentation of these 16O,12C beams. The detector includes a magnetic spectrometer based on silicon pixel detectors and drift chamber, a scintillating crystal calorimeter with TOF capabilities, able to stop the heavier fragments produced, and a ΔE detector to achieve the needed energy resolution and particle identification. An alternative setup of the experiment will exploit the emulsion chamber capabilities. A specific emulsion chambers will be coupled with the interaction region of the FOOT setup to measure the production in target fragmentation of light charged fragments as protons, deuterons, tritons and Helium nuclei. The FOOT data taking is foreseen at the CNAO experimental room and will start during early 2018 with the emulsion setup, while the complete electronic detector will take data since 2019.