The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes ...and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.
The use of protons and heavy ions for the treatment of tumors is increasing since it provides a better relative biological effectiveness (RBE) than traditional radiotherapy. Accurate knowledge of the ...energy deposition at submicrometric scales is paramount for RBE characterization. This paper shows the latest version of the silicon cylindrical microdosimeter array developed by the Instituto de Microelectrónica de Barcelona, Centro Nacional de Microelectrónica (IMB-CNM, Spain). The detector consists of a matrix of <inline-formula> <tex-math notation="LaTeX">11 \times 11 </tex-math></inline-formula> cylindrical sensitive unit cells with individual readout etched within the silicon substrate available in different diameters and pitches between detectors. The detector employed in this paper had a diameter of <inline-formula> <tex-math notation="LaTeX">15~\mu \text{m} </tex-math></inline-formula>, a pitch of <inline-formula> <tex-math notation="LaTeX">200~\mu \text{m} </tex-math></inline-formula>, and a thickness of <inline-formula> <tex-math notation="LaTeX">5.5~\mu \text{m} </tex-math></inline-formula>. The detectors were tested in the clinical facilities of Fondazione Centro Nazionale di Adronterapia Oncologica (CNAO) (Pavia, Italy) employing a 12 C pencil beam at a therapeutic beam fluence rate. Microdosimetric spectra of lineal energy were measured in different depths of polymethyl methacrylate (PMMA) up to the Bragg peak. Results were then compared with Monte Carlo simulations using the FLUKA particle transport code, showing an excellent agreement between experimental and simulated microdosimetric distributions even at the high fluence rates associated with clinical beams.
From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve ...tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.
Si les définitions de la radiorésistance des tumeurs peuvent varier selon l’angle de vue, radiobiologique ou clinique, les mécanismes de la radiorésistance sont partiellement identifiés. Ils impliquent des voies de signalisation oncogènes spécifiques aux tumeurs, le métabolisme et la prolifération des tumeurs, le microenvironnement tumoral/hypoxie, et peuvent reposer sur une génomique somatique spécifique. Les corrélations entre la biologie des tumeurs (histologie) et l’imagerie permettent des approches théragnostiques qui utilisent une imagerie biologique non invasive (fonctionnalisation de traceurs des biomarqueurs des voies tumorales, imagerie de l’hypoxie, etc). La modélisation de la fonction de prescription des doses en fonction de leur rapport d’amélioration d’un facteur de radiorésistance des tumeurs, lié au métabolisme, à la prolifération, à l’hypoxie est un domaine en cours d’investigations. Pourtant, la délivrance d’une irradiation très modulée, voxel par voxel, avec des particules à faible transfert d’énergie linéal, peut être limitée par le degré de complexité de la modulation nécessaire pour obtenir les doses requises pour contrer la radiorésistance tumorale. Des particules à transfert d’énergie linéal plus élevé ou des combinaisons de différentes particules, ou des combinaisons avec des médicaments et dispositifs comme celles réalisées avec des nanoparticules améliorant la radioprotection peuvent être envisagées.
The FragmentatiOn mymargin Of Target (FOOT) experiment aims to provide precise nuclear cross section measurements for two different fields: hadrontherapy and radio-protection in space. The main ...reason is the important role the nuclear fragmentation process plays in both fields, where the health risks caused by radiation are very similar and mainly attributable to the fragmentation process. The FOOT experiment has been developed in such a way that the experimental setup is easily movable and fits the space limitations of the experimental and treatment rooms available in hadrontherapy treatment centers, where most of the data takings are carried out. The trigger and data acquisition system needs to follow the same criteria and it should work in different laboratories and different conditions. It has been designed to acquire high statistics samples to fulfill the accuracy requirements of the physics analysis. Data-taking is being monitored online to allow the shift crew to verify the correct functioning of the system.
Purpose
The real‐time monitoring of the spread‐out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam ...therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt‐γ produced by the interactions of the 12C ion beam with a polymethyl methacrylate (PMMA) target. We also assess three different Monte Carlo models for prompt‐γ simulation based on our experimental data.
Methods
The experiment was carried out at the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany with a 220 MeV/u 12C ions beam impinging on a 5× 5× 20 cm3 polymethyl methacrylate beam stopping target, with the prompt‐γ being detected by a hexagonally‐shaped barium fluoride scintillator with a circumscribed radius of 5.4 cm and a length of 14 cm, placed at 60° and 90° with respect to the beam direction. Monte Carlo simulations were carried out with three different hadronic models from the Geant4 code: binary ion cascade (BIC), quantum molecular dynamics (QMD), and Liege intranuclear cascade (INCL++).
Results
An experimental prompt‐γ yield of 1.06 × 10−2 sr−1 was measured at 90°. A good agreement was observed between the shapes of the experimental and simulated energy spectra, especially with the INCL++ physics list. The prompt‐γ yield obtained with this physics list was compatible with the measurement within 2σ, with a relative difference of 26% on average. BIC and QMD physics lists proved to be less accurate than INCL++, with the difference between the measured and simulated yields exceeding 100%. The differences between the three physics lists were ascribed to important discrepancies between the models of the physical processes producing prompt‐γ emissions.
Conclusion
In conclusion, this study provides prompt‐γ yield values in agreement with previously published results for different carbon ions energies. This work demonstrates that the INCL++ physics list from Geant4 is more accurate than BIC and QMD to reproduce prompt‐γ emission properties.
As a biologist who, since the beginning of her involvement in science, has collaborated closely with physicists, I want to share my forty years of experience describing the events that introduced me ...to the world of charged particle radiation biology as well as that of low doses/dose rates, with related implications in medicine and radiation protection.
The main features of my experience can be summarized in the development of an interdisciplinary culture and in the interest in technological advances for the study of biological responses to radiation in different scenarios, relevant for public health. Mine was a journey that began by chance, but which led me to a world that proved to be of great interest to me. With the current advances in science, the new generations of scientists have new opportunities that I wish them to face with the same interest and enthusiasm that I felt for such an interdisciplinary field as that of radiation biology.
The commissioning of an ion beam for hadrontherapy requires the evaluation of the biologically weighted effective dose that results from the microdosimetric properties of the therapy beam. The ...spectra of the energy imparted at cellular and sub-cellular scales are fundamental to the determination of the biological effect of the beam. These magnitudes are related to the microdosimetric distributions of the ion beam at different points along the beam path. This work is dedicated to the measurement of microdosimetric spectra at several depths in the central axis of a (12)C beam with an energy of 94.98 AMeV using a novel 3D ultrathin silicon diode detector. Data is compared with Monte Carlo calculations providing an excellent agreement (deviations are less than 2% for the most probable lineal energy value) up to the Bragg peak. The results show the feasibility to determine with high precision the lineal energy transfer spectrum of a hadrontherapy beam with these silicon devices.
Hadrontherapy is a form of radiation therapy (RT) that relies on heavy particles, such as proton, heavy ions, or neutrons, to enhance anti-tumoral efficacy based on their specific dosimetric and ...radio-biological properties. Neutrons are characterized by specific radiobiological properties that might deserve greater consideration, including the high linear energy transfer and the low oxygen enhancement ratio. Neutron brachytherapy, relying on interstitial or intracavitary neutron sources, has been developed since the 1950s using Californium-252 (252Cf) as a mixed emitter of fission fast neutrons and γ-photos. However, the place of NBT in the era of modern radiation therapy is yet to be precisely defined. In this systematic review, we aim to provide an up-to-date analysis of current experience and clinical evidence of NBT in the XXI th century, by answering the following clinical questions: How is NBT currently delivered? What are the current efficacy data and tolerance profiles of NBT?
L’hadronthérapie est une technique de radiothérapie basée sur des faisceaux de particules, comme les protons, les ions lourds ou les neutrons, afin d’augmenter l’efficacité antitumorale en exploitant leurs propriétés radiobiologiques et dosimétriques particulières. Les neutrons sont caractérisées par des propriétés radiobiologiques spécifiques : un transfert linéique d’énergie élevé et un effet d’amélioration de l’oxygène faible. La curiethérapie par neutrons a été développée dans les années 1950, utilisant le Californium-252 comme émetteur mixte de neutrons rapides et de photons gamma. Néanmoins, la place de la curiethérapie par neutrons au 21e siècle doit être précisée. Dans cette revue systématique, nous avons cherché à préciser les indications actuelles et le niveau de preuve de la curiethérapie par neutrons.
Proton imaging can be seen as a powerful technique for online monitoring of ion range during carbon ion therapy irradiations. Indeed, a large number of secondary protons are created during nuclear ...reactions, and many of these protons are likely to escape from the patient even for deep-seated tumors, carrying accurate information on the reaction vertex position. Two detection techniques have been considered: (i) double-proton detection by means of two forward-located trackers and (ii) single-proton detection in coincidence with the incoming carbon ion detected by means of a beam hodoscope. Geant4 simulations, validated by proton yield measurements performed at GANIL and GSI, show that ion-range monitoring is accessible on a pencil-beam basis with the single-proton imaging technique. Millimetric precision on the Bragg peak position is expected in the ideal case of homogeneous targets. The uncertainties in more realistic conditions should be investigated, in particular the influence of tissue heterogeneity in the very last part of the ion path (about 20 mm).
The quality assurance of particle therapy treatment is a fundamental issue that can be addressed by developing reliable monitoring techniques and indicators of the treatment plan correctness. Among ...the available imaging techniques, positron emission tomography (PET) has long been investigated and then clinically applied to proton and carbon beams. In 2013, the Innovative Solutions for Dosimetry in Hadrontherapy (INSIDE) collaboration proposed an innovative bimodal imaging concept that combines an in-beam PET scanner with a tracking system for charged particle imaging. This paper presents the general architecture of the INSIDE project but focuses on the in-beam PET scanner that has been designed to reconstruct the particles range with millimetric resolution within a fraction of the dose delivered in a treatment of head and neck tumors. The in-beam PET scanner has been recently installed at the Italian National Center of Oncologic Hadrontherapy (CNAO) in Pavia, Italy, and the commissioning phase has just started. The results of the first beam test with clinical proton beams on phantoms clearly show the capability of the in-beam PET to operate during the irradiation delivery and to reconstruct on-line the beam-induced activity map. The accuracy in the activity distal fall-off determination is millimetric for therapeutic doses.
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