A new detector for the beam energy measurement in proton therapy: a feasibility study.

The proof of concept of a new device, capable of determining in a few seconds the energy of clinical proton beams by measuring the time of flight (ToF) of protons, is presented. The prototype consists of two thin ultra fast silicon detector (UFSD) pads, aligned along the beam direction in a telescope configuration and readout by a digitizer. The method developed for extracting the energy at the isocenter from the measured ToF, validated by Monte Carlo simulations, and the procedure used to calibrate the system are also presented and discussed in detail. The prototype was tested at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy), at several beam energies, covering the entire clinical range, and using different distances between the sensors. The measured beam energies were benchmarked against the nominal CNAO energy values, obtained during the commissioning of the centre from the measured ranges in water. Deviations of few hundreds of keV have been achieved for all considered proton beam energies for distances between the two sensors larger than 60 cm, indicating a sensitivity to the corresponding beam range in water smaller than the clinical tolerance of 1 mm. Moreover, few seconds of irradiation were necessary to collect the required statistics. These preliminary results indicate that a telescope of UFSDs could achieve in a short time the accuracy required for the clinical application and therefore encourage further investigations towards the improvement and the optimization of the present prototype.

RIDOS: A new system for online computation of the delivered dose distributions in scanning ion beam therapy.

PURPOSE: To describe a new system for scanned ion beam therapy, named RIDOS (Real-time Ion DOse planning and delivery System), which performs real time delivered dose verification integrating the information from a clinical beam monitoring system with a Graphic Processing Unit (GPU) based dose calculation in patient Computed Tomography. METHODS: A benchmarked dose computation algorithm for scanned ion beams has been parallelized and adapted to run on a GPU architecture. A workstation equipped with a NVIDIA GPU has been interfaced through a National Instruments PXI-crate with the dose delivery system of the Italian National Center of Oncological Hadrontherapy (CNAO) to receive in real-time the measured beam parameters. Data from a patient monitoring system are also collected to associate the respiratory phases with each spot during the delivery of the dose. Using both measured and planned spot properties, RIDOS evaluates during the few seconds of inter-spill time the cumulative delivered and prescribed dose distributions and compares them through a fast γ-index algorithm. RESULTS: The accuracy of the GPU-based algorithms was assessed against the CPU-based ones and the differences were found below 1‰. The cumulative planned and delivered doses are computed at the end of each spill in about 300 ms, while the dose comparison takes approximatively 400 ms. The whole operation provides the results before the next spill starts. CONCLUSIONS: RIDOS system is able to provide a fast computation of the delivered dose in the inter-spill time of the CNAO facility and allows to monitor online the dose deposition accuracy all along the treatment.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

'Survival': a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy.

One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named 'Survival', to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

Review of technologies and procedures of clinical dosimetry for scanned ion beam radiotherapy.

In the last few years, the use of ions in radiation therapy is gaining interest and it is being considered medically necessary for a growing subset of tumours. Concurrently, the technologies involved in a particle therapy treatment are rapidly evolving, as well as the accuracy in the dose delivery in spite of the increased complexity. Since nowadays, the pencil beam scanning technique is showing very interesting features in terms of dose conformation and overall treatment outcome, the present review is intended to summarize the main procedures, detectors and tools adopted for the clinical dose verification. A list of dose measurements is provided, with the aim of being a valuable guidance for starting and future particle therapy facilities. Absorbed dose to water, relative dose, fluence and surrogates of the delivered dose are the main quantities measured by means of different detectors, specifically developed for point-like, 1D or 2D measurements. The dosimetric procedures are here categorized according to their purpose, distinguishing between system commissioning and clinical quality assurance. A separate discussion is dedicated to patient specific, in vivo and 4D dose verification, which aim at assessing the actual delivered dose. Together with the description of the currently used methods, challenges and perspectives toward an increasingly accurate and fast dose verification strategy are discussed.

Quality assurance of carbon ion and proton beams: A feasibility study for using the 2D MatriXX detector.

PURPOSE: The quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements. METHODS: MatriXX is a commercial detector composed of 32×32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44MeV proton and a 221.45MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia - Italy, and the results were analyzed and compared. RESULTS: The sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230µm for carbon ions and less than 100µm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement. CONCLUSIONS: The results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.

Dosimetric commissioning and quality assurance of scanned ion beams at the Italian National Center for Oncological Hadrontherapy.

PURPOSE: To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy. METHODS: The laterally integrated depth-dose-distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. fluka Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D-fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer-type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread-out-Bragg-peak, dose homogeneity in 2D-fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines. RESULTS: The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy-dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ± 1 mm over the whole 20 × 20 cm(2) scan field; homogeneity in a uniform squared field was within ± 5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns. CONCLUSIONS: After successful dosimetric beam commissioning, quality assurance measurements performed during a 24-month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments.

The CNAO dose delivery system for modulated scanning ion beam radiotherapy.

PURPOSE: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. METHODS: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. RESULTS: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity. CONCLUSIONS: The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness.

The relative biological effectiveness (RBE) concept is commonly used in treatment planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data can be used to predict human response to treatments is an open issue. In this work an alternative method, based on an effective radiobiological parameterization directly derived from clinical data, is presented. The method has been applied to the analysis of prostate cancer trials with protons and carbon ions.Prostate cancer trials with proton and carbon ion beams reporting 5 year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates (TOX) were selected from literature to test the method. Treatment simulations were performed on a representative subset of patients to produce dose and linear energy transfer distribution, which were used as explicative physical variables for the radiobiological modelling. Two models were taken into consideration: the microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological parameters of the LM and MKM were obtained by coupling them with the tumor control probability and normal tissue complication probability models to fit the LC5 and TOX data through likelihood maximization. The model ranking was based on the Akaike information criterion.Results showed large confidence intervals due to the limited variety of available treatment schedules. RBE values, such as RBE = 1.1 for protons in the treated volume, were derived as a by-product of the method, showing a consistency with current approaches. Carbon ion RBE values were also derived, showing lower values than those assumed for the original treatment planning in the target region, whereas higher values were found in the bladder. Most importantly, this work shows the possibility to infer the radiobiological parametrization for proton and carbon ion treatment directly from clinical data.

Dosimetric accuracy assessment of a treatment plan verification system for scanned proton beam radiotherapy: one-year experimental results and Monte Carlo analysis of the involved uncertainties.

During one year of clinical activity at the Italian National Center for Oncological Hadron Therapy 31 patients were treated with actively scanned proton beams. Results of patient-specific quality assurance procedures are presented here which assess the accuracy of a three-dimensional dose verification technique with the simultaneous use of multiple small-volume ionization chambers. To investigate critical cases of major deviations between treatment planning system (TPS) calculated and measured data points, a Monte Carlo (MC) simulation tool was implemented for plan verification in water. Starting from MC results, the impact of dose calculation, dose delivery and measurement set-up uncertainties on plan verification results was analyzed. All resulting patient-specific quality checks were within the acceptance threshold, which was set at 5% for both mean deviation between measured and calculated doses and standard deviation. The mean deviation between TPS dose calculation and measurement was less than ±3% in 86% of the cases. When all three sources of uncertainty were accounted for, simulated data sets showed a high level of agreement, with mean and maximum absolute deviation lower than 2.5% and 5%, respectively.

SU-E-T-298: Evaluation of the CNAO Spot Scanning Technique Based on the First Clinical Deliveries.

PURPOSE: The first Italian hospital-based facility for hadrontherapy is the Centro Nazionale di Adroterapia Oncologica (CNAO) which started the clinical activity on September 2011 with protons beams. The control of the treatment is performed online by the Dose Delivery (DD) system which guides the whole treatment by measuring beam characteristics as number of delivered particles and beam position. The author will present the comparison between the required and delivered quantities. METHODS: The CNAO facility is based on a synchrotron designed to accelerate and deliver proton and carbon ion beams in the clinical ranges. Unlike most of the proton-therapy centres, the delivery technique adopted at CNAO is the "quasi-discrete" active scanning where dedicated magnets are used to drive a pencil beam through the target and the beam is normally not switched off during the transition between adjacent spots. These operations are performed by the DD system which, based on the treatment planning and the online analysis of dedicated beam monitor chambers, drives the scanning magnets. Spot by spot the DD records data which allow the comparison between the measured number of particles and position and the prescription. RESULTS: The data collected by the dose delivery during the treatments were analyzed in detail, each treatment consisting in more than 30 identical fractions. This allows checking the stability and the accuracy of the CNAO delivery over identical spot sequences. The comparison between the measured number of particles, the measured position of each spot, and the corresponding prescribed quantities will be presented in detail. Critical points will be discussed together with the proposed improvement of the system. CONCLUSIONS: The results confirm the good performance of the CNAO beam delivery obtained during the commissioning phase.

Online beam monitoring in the treatment of ocular pathologies at the INFN Laboratori Nazionali del Sud-Catania.

A detector (MOPI) has been developed for the online monitoring of the beam at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA), where shallow tumours of the ocular region are treated with 62 MeV protons. At CATANA the beam is passively spread to match the tumour shape. The uniformity of the delivered dose depends on beam geometrical quantities which are checked before each treatment. However, beam instabilities might develop during the irradiation affecting the dose distribution. This paper reports on the use of the MOPI detector to measure the stability of the beam profile during the irradiation in the clinical practice. The results obtained in the treatment of 54 patients are also presented.

Heuristic optimization of the scanning path of particle therapy beams.

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

A treatment planning code for inverse planning and 3D optimization in hadrontherapy.

The therapeutic use of protons and ions, especially carbon ions, is a new technique and a challenge to conform the dose to the target due to the energy deposition characteristics of hadron beams. An appropriate treatment planning system (TPS) is strictly necessary to take full advantage. We developed a TPS software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is an analytical code using the voxel-scan technique as an active method to deliver the dose to the patient, and provides treatment plans with both proton and carbon ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux platform, allows the determination of the best fluences of the individual beams to obtain an optimal physical dose distribution, delivering a maximum dose to the target volume and a minimum dose to critical structures. The TPS is supported by Monte Carlo simulations with the package GEANT3 to provide the necessary physical lookup tables and verify the optimized treatment plans. Dose verifications done by means of full Monte Carlo simulations show an overall good agreement with the treatment planning calculations. We stress the fact that the purpose of this work is the verification of the physical dose and a next work will be dedicated to the radiobiological evaluation of the equivalent biological dose.

A method for the inter-calibration of a matrix of sensors.

We present a quick and easy method for the calibration of a matrix of sensors. The algorithm is based on a three-step irradiation procedure which relies only on the constancy of the delivered fluence at each step. With this method the gain of each sensor is derived relative to a reference detector. The algorithm has been applied to a matrix of (32 x 32) ionization chambers. After the calibration coefficients have been applied, by comparing the response of the matrix of chambers to a reference detector over a large field, we determined that the fluence measurement of individual chambers is better than 0.7%. The algorithm solves the cumbersome problem of the relative gain calibration of a matrix of a large number of sensors.

D-IMRT verification with a 2D pixel ionization chamber: dosimetric and clinical results in head and neck cancer.

Dynamic intensity-modulated radiotherapy (D-IMRT) using the sliding-window technique is currently applied for selected treatments of head and neck cancer at Institute for Cancer Research and Treatment of Candiolo (Turin, Italy). In the present work, a PiXel-segmented ionization Chamber (PXC) has been used for the verification of 19 fields used for four different head and neck cancers. The device consists of a 32x32 matrix of 1024 parallel-plate ionization chambers arranged in a square of 24x24 cm2 area. Each chamber has 0.4 cm diameter and 0.55 cm height; a distance of 0.75 cm separates the centre of adjacent chambers. The sensitive volume of each single ionization chamber is 0.07 cm3. Each of the 1024 independent ionization chambers is read out with a custom microelectronics chip.The output factors in water obtained with the PXC at a depth of 10 cm were compared to other detectors and the maximum difference was 1.9% for field sizes down to 3x3 cm2. Beam profiles for different field dimensions were measured with the PXC and two other types of ionization chambers; the maximum distance to agreement (DTA) in the 20-80% penumbra region of a 3x3 cm2 field was 0.09 cm. The leaf speed of the multileaf collimator was varied between 0.07 and 2 cm s-1 and the detector response was constant to better than 0.6%. The behaviour of the PXC was measured while varying the dose rate between 0.21 and 1.21 Gy min-1; the mean difference was 0.50% and the maximum difference was 0.96%. Using fields obtained with an enhanced dynamic wedge and a staircase-like (step) IMRT field, the PXC has been tested for simple 1D modulated beams; comparison with film gave a maximum DTA of 0.12 cm. The PXC was then used to check four different IMRT plans for head and neck cancer treatment: cervical chordoma, parotid, ethmoid and skull base. In the comparison of the PXC versus film and PXC versus treatment planning system, the number of pixels with gamma parameter

Two-dimensional and quasi-three-dimensional dosimetry of hadron and photon beams with the Magic Cube and the Pixel Ionization Chamber.

Two detectors for fast two-dimensional (2D) and quasi-three-dimensional (quasi-3D) verification of the dose delivered by radiotherapy beams have been developed at University and Istituto Nazionale di Fisica Nucleare (INFN) of Torino. The Magic Cube is a stack of strip-segmented ionization chambers interleaved with water-equivalent slabs. The parallel plate ionization chambers have a sensitive area of 24 x 24 cm2, and consist of 0.375 cm wide and 24 cm long strips. There are a total of 64 strips per chamber. The Magic Cube has been tested with the clinical proton beam at Loma Linda University Medical Centre (LLUMC), and was shown to be capable of fast and precise quasi-3D dose verification. The Pixel Ionization Chamber (PXC) is a detector with pixel anode segmentation. It is a 32 x 32 matrix of 1024 cylindrical ionization cells arranged in a square 24 x 24 cm2 area. Each cell has 0.4 cm diameter and 0.55 cm height, at a pitch of 0.75 cm separates the centre of adjacent cells. The sensitive volume of each single ionization cell is 0.07 cm3. The detectors are read out using custom designed front-end microelectronics and a personal computer-based data acquisition system. The PXC has been used to verify dynamic intensity-modulated radiotherapy for head-and-neck and breast cancers.

Dosimetric characterization of a large area pixel-segmented ionization chamber.

A pixel-segmented ionization chamber has been designed and built by Torino University and INFN. The detector features a 24 x 24 cm2 active area divided in 1024 independent cylindrical ionization chambers and can be read out in 500 micros without introducing dead time; the digital charge quantum can be adjusted between 100 fC and 800 fC. The sensitive volume of each single ionization chamber is 0.07 cm3. The purpose of the detector is to ease the two-dimensional (2D) verifications of fields with complex shapes and large gradients. The detector was characterized in a PMMA phantom using 60Co and 6 MV x-ray photon beams. It has shown good signal linearity with respect to dose and dose rate to water. The average sensitivity of a single ionization chamber was 2.1 nC/Gy, constant within 0.5% over one month of daily measurements. Charge collection efficiency was 0.985 at the operating polarization voltage of 400 V and 3.5 Gy/min dose rate. Tissue maximum ratio and output factor have been compared with a Farmer ionization chamber and were found in good agreement. The dose profiles have been compared with the ones obtained with an ionization chamber in water phantom for the field sizes supplied by a 3D-Line dynamic multileaf collimator. These results show that this detector can be used for 2D dosimetry of x-ray photon beams, supplying a good spatial resolution and sensibly reducing the time spent in dosimetric verification of complex radiation fields.