Prompt-gamma fall-off estimation with C-ion irradiation at clinical energies, using a knife-edge slit camera: A Monte Carlo study.

PURPOSE: In-vivo range verification has been a hot topic in particle therapy since two decades. Many efforts have been done for proton therapy, while fewer studies were conducted considering a beam of carbon ions. In the present work, a simulation study was performed to show whether it is possible to measure the prompt-gamma fall-off inside the high neutron background typical of carbon-ion irradiation, using a knife-edge slit camera. In addition to this, we wanted to estimate the uncertainty in retrieving the particle range in the case of a pencil beam of C-ions at clinically relevant energy of 150 MeVu. METHODS: For these purposes, the Monte Carlo code FLUKA was adopted for simulations and three different analytical methods were implemented to get the accuracy in the range retrieval of the simulated set-up. RESULTS: The analysis of simulation data has brought to the promising and desired precision of about 4 mm in the determination of the dose profile fall-off in case of a spill irradiation, for which all the three cited methods were coherent in their predictions. CONCLUSIONS: The Prompt Gamma Imaging technique should be further studied as a tool to reduce range uncertainties affecting carbon ion radiation therapy.

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives.

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

Mixed particle beam for simultaneous treatment and online range verification in carbon ion therapy: Proof-of-concept study.

PURPOSE: Radiation therapy with ion beams provides a better conformation and effectiveness of the dose delivered to the tumor with respect to photon beams. This implies that a small uncertainty or variation in the crossed tissue shape and density may lead to a more important underdosage of the tumor and/or an overdosage of the surrounding healthy tissue. Although the online control of beam fluence and transverse position is well managed by an appropriate beam delivery system, the online measurement of the longitudinal position of the Bragg peak inside the patient is still an open issue. In this paper we propose a proof-of-concept study of a technique that would allow the online verification of the patient thickness along the beam direction, which could permit detecting a subset of possible range error causes, such as morphological variations. METHODS: The nuclei 12 C and 4 He have the same magnetic rigidity: the two species could be accelerated together in an accelerator and a mixed particle beam delivered to the patient. In the same medium and with the same energy per nucleon, the range of 4 He2+ is about three times the 12 C6+ one. It is, thus, conceivable to achieve a dual goal with a single mixed beam: carbon, stopping into the tumor, is appointed to cure, while helium, emerging from the patient, to control: by detecting and measuring the residual range and position of He, it would be possible to determine the integrated relative stopping power of the patient and prove that it is the expected one. For the detection of helium particles, a plastic scintillator and an optical sensor are proposed. Being helium ions not available at CNAO, the detection system has been characterized using a proton beam. Nevertheless, since the light emitted by a proton is less than the one produced by a helium ion, the helium signal is expected to be more pronounced than the proton one (for the same number of particles). To predict the magnitude of the light signal measured by the sensor, two Monte Carlo models have been setup and validated by measuring the photons per pixel impinging on the sensor. To deal with the many optical issues and to reliably describe the physical process, some corrections have been included into the models. RESULTS: The predictions of both the models are in good agreement with the measurements (within the 20% in terms of absolute photons per pixel). The proposed detection system is able to measure the range of a proton beam with sub-millimetrical precision also in the presence of the background produced by carbon ion fragments and discrepancies in the expected range were detected with a resolution better than 1 mm. CONCLUSIONS: Although many technical issues have still to be addressed for a real implementation in a clinical environment, the preliminary results of this study suggest that a surrogate of real-time verification of the beam range inside the patient during a treatment with carbon ions is possible by adding a small fraction of helium ions to the primary beam.

Shielding of proton accelerators.

This paper discusses some of the methods that can be employed for calculating shielding of proton accelerators, showing that a simple analytical model is often useful for a first estimate before going into complex Monte Carlo simulations. In particular what we call the Monte Carlo 'hybrid' approach, which employs source terms and attenuation length data calculated by Monte Carlo simulations under generic geometrical conditions, with a point-source line-of-sight model is discussed. Examples are given of the application of this method to the shielding calculations of two versions of the CERN SPL (2- and 3.5-GeV energy), comparing its results with Monte Carlo simulations of the full geometry.

Silicon microdosimetry.

Silicon detectors are being studied as microdosemeters since they can provide sensitive volumes of micrometric dimensions. They can be applied for assessing single-event effects in electronic instrumentation exposed to complex fields around high-energy accelerators or in space missions. When coupled to tissue-equivalent converters, they can be used for measuring the quality of radiation therapy beams or for dosimetry. The use of micrometric volumes avoids the contribution of wall effects to the measured spectra. Further advantages of such detectors are their compactness, cheapness, transportability and a low sensitivity to vibrations. The following problems need to be solved when silicon devices are used for microdosimetry: (i) the sensitive volume has to be confined in a region of well-known dimensions; (ii) the electric noise limits the minimum detectable energy; (iii) corrections for tissue-equivalency should be made; (iv) corrections for shape equivalency should be made when referring to a spherical simulated site of tissue; (v) the angular response should be evaluated carefully; (vi) the efficiency of a single detector of micrometric dimensions is very poor and detector arrays should be considered. Several devices have been proposed as silicon microdosemeters, based on different technologies (telescope detectors, silicon on insulator detectors and arrays of cylindrical p-n junctions with internal amplification), in order to satisfy the issues mentioned above.

RBE estimation of proton radiation fields using a DeltaE-E telescope.

A new monolithic silicon DeltaE-E telescope was evaluated in unmodulated and modulated 100 MeV proton beams used for hadron therapy. Compared to a classical microdosimetry detector, which provides one-dimensional information on lineal energy of charged particles, this detector system provides two-dimensional information on lineal energy and particle energy based on energy depositions, collected in coincidence, within the DeltaE and E stages of the detector. The authors investigated the possibility to use the information obtained with the DeltaE-E telescope to determine the relative biological effectiveness (RBE) at defined locations within the proton Bragg peak and spread-out Bragg peak (SOBP). An RBE matrix based on the established in vitro V79 cell survival data was developed to link the output of the device directly to RBE(alpha), the RBE in the low-dose limit, at various depths in a homogeneous polystyrene phantom. In the SOBP of a 100 MeV proton beam, the RBE(alpha) increased from 4.04 proximal to the SOBP to a maximum value of 5.4 at the distal edge. The DeltaE-E telescope, with its high spatial resolution, has potential applications to biologically weighted hadron treatment planning as it provides a compact and portable means for estimating the RBE in rapidly changing hadron radiation fields within phantoms.

Instrument response in complex radiation fields.

This paper aims at giving an overview of the main issues for estimating the radiation protection quantities in complex radiation fields. The measurability (or non-measurability) of the radiation protection quantities is discussed together with the main approaches for their estimate. The main mechanisms through which the various components of complex radiation fields are generated are also outlined. The main instruments employed for estimating the radiation protection quantities are described and discussed together with their response. Finally, a practical example is given, by discussing the results of an inter-comparison exercise held at the Gesellschaft für Schwerionenforschung mbH in Darmstadt (Germany) in the framework of the COordinated Network for RAdiation Dosimetry project, funded by the European Commission.

Radiation protection constraints for use of proton and ion accelerators in medicine.

This paper gives some guidelines for radiation protection at proton therapy facilities. The energy and angular distribution of secondary radiation from thick iron and tissue targets bombarded by 250-MeV protons were calculated with Monte Carlo simulations in order to emphasise the influence of the various components of the radiation field on the shielding design. The main constraints for radiation protection (e.g. workload, use and occupancy factors, etc.), shielding design (including access mazes) and the estimate of material activation are also discussed with some practical examples.

Analysis of computational problems expressing the overall uncertainties: photons, neutrons and electrons.

In the frame of the EU Coordination Action CONRAD (coordinated network for radiation dosimetry), WP4 was dedicated to work on computational dosimetry with an action entitled 'Uncertainty assessment in computational dosimetry: an intercomparison of approaches'. Participants attempted one or more of eight problems. This paper presents the results from problems 4-8-dealing with the overall uncertainty budget estimate; a short overview of each problem is presented together with a discussion of the most significant results and conclusions. The scope of the problems discussed here are: the study of a (137)Cs calibration irradiator; the manganese bath technique; the iron sphere experiment using neutron time-of-flight technique; the energy response of a RADFET detector and finally the sensitivity and uncertainty analysis for the recoil-proton telescope discussed in the companion paper.

Monte Carlo simulations for the design of the treatment rooms and synchrotron access mazes in the CNAO Hadrontherapy facility.

The Italian National Centre for Hadrontherapy is based on a synchrotron capable of accelerating protons and carbon ions up to 250 MeV and 400 MeV u(-1), respectively. The present work describes some Monte Carlo simulations performed to verify the design of the treatment rooms and synchrotron access mazes. The different shielding efficiency and induced activations of the common concrete and the baryte concrete were analysed. In such a radiation field, i.e. with high-energy neutrons, the baryte concrete gains twice the activation than the common concrete without any relevant dose reduction. Moreover, the simulations have stressed, again, the discrepancies between H*(10) and E in such cases where the neutron radiation field is the dominant component and, particularly, in the medium-high energy range.

Measurements of radiation fields around high-energy proton accelerators.

Monitoring of ionising radiation around high-energy particle accelerators is a difficult task due to the complexity of the radiation field, which is made up of neutrons, charged hadrons, muons, photons and electrons, with energy spectra extending over a wide energy range. The dose-equivalent outside a thick shield is mainly owing to neutrons, with some contribution from photons and, to a minor extent, the other particles. Neutron dosimetry and spectrometry are thus of primary importance to correctly evaluate the exposure of personnel. This paper reviews the relevant techniques and instrumentation employed for monitoring radiation fields around high-energy proton accelerators, with particular emphasis on the recent development to increase the response of neutron measuring devices > 20 MeV. Rem-counters, pressurised ionisation chambers, superheated emulsions, tissue-equivalent proportional counters and Bonner sphere spectrometers are discussed.

Secondary neutron dose during proton therapy using spot scanning.

PURPOSE: During proton radiotherapy, secondary neutrons are produced by nuclear interactions in the material in the beam line before and after entering the patient. The dose equivalent deposited by these neutrons is usually not considered in routine treatment planning. In this study, we estimated the neutron dose in patients from a spot scanning beam line by performing measurements and Monte Carlo simulations. METHODS AND MATERIALS: Measurements of the secondary neutron dose were performed during irradiation of a water phantom with 177-MeV protons using a Bonner sphere and CR39 etch detectors. Additionally, Monte Carlo simulations were performed using the FLUKA code. RESULTS: A comparison of our measurements with measurements taken at a beam line using the scatter foil technique shows a dose advantage of at least 10 for the spot scanning technique. In the region of the Bragg peak, the neutron dose equivalent can reach for a medium-sized target volume approximately 1% of the treatment dose. Neutron doses expected in healthy tissues of the patient (in the not-treated volume) are for large and medium target volumes, approximately 0.004 Sv and 0.002 Sv per treatment Gy, respectively. CONCLUSIONS: We conclude from the measurements and simulations that the dose deposited by secondary neutrons during proton radiotherapy using the spot scanning technique can be neglected in the treatment region. In the healthy tissue, the dose coming from neutrons (0.002 Sv per treatment Gy) is approximately a factor of two larger than during photon treatment (0.001 Sv). These contributions to the integral dose from neutrons are still very low when compared to the dose sparing that can be achieved by using a proton beam instead of photons.