PHYSICAL AND DOSIMETRIC BEAM CHARACTERISATION PROTOCOL AT CENTRO NAZIONALE DI ADROTERAPIA ONCOLOGICA (CNAO)

Transcription

1 Project co-funded by the European Commission within the FP7 ( ) ULICE Union of Light Centres in Europe Page 1 of 27

2 PHYSICAL AND DOSIMETRIC BEAM CHARACTERISATION PROTOCOL AT CENTRO NAZIONALE DI ADROTERAPIA ONCOLOGICA (CNAO) Authors: Mario Ciocca 1, Alfredo Mirandola 1, Silvia Molinelli 1, Gloria Vilches Freixas 1, Faiza Bourhaleb 1,2, Andrea Mairani 1, Luigi Raffaele 1,3 1 CNAO: Centro Nazionale di Adroterapia Oncologica, Italy; 2 I-SEE Co., Italy; 3 Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele, Italy 1 Introduction The physical and dosimetric beams characterisation is mandatory in the prospective of patients treatment with particles radiation therapy. In particular an accurate knowledge of the beam characteristics, of the standardised procedures and adopted equipments, as well as the arrangement of a specific and systematic quality assurance protocol, is needed in order to fully exploit the potential advantages of the particles radiation therapy, warranting at the same time, the safety of the patients. In an initial phase of CNAO activities, high energy light ions (protons and carbon ions) will be delivered using quasi-discrete active scanning, changing the beam energy spill by spill. Other ions like He 2+, Li 3+, Be 4+, B 5+, 0 8 will be employed in the next future. Particle beams are accelerated in the synchrotron ring and extracted towards one of the three treatment rooms currently equipped; protons energy varies from 60 to 250 MeV, whereas carbon ions energy varies from 120 to 400 MeV/u. The corresponding depths in water covers up to 27 cm with 1 mm step, fulfilling the clinical requests. The homogeneity of the dose distribution in z-direction is obtained generating the so called SOBP, (Spread Out Bragg Peak) obtained by the superimposition of many pristine Bragg peaks. CNAO beam size will have a full width half maximum at the isocenter (FWHM) iso ranging from 4 to 10 mm, with 1 mm step. For every isoenergetic slice, corresponding to a specific depth, pencil beam will be moved in x and y direction by two scanning magnets; in this way the target will be irradiated spot by spot. During scan of adjacent spots, the beam will not be generally switched off. In order to guarantee the patients safety, the adoption of a dose delivery system as sophisticated and reliable as the active scanning method implemented, is necessary: at CNAO facility every treatment line will be equipped with a device (nozzle) located immediately before the patient. Page 2 of 27

3 The nozzle is composed of two independent dosimetric devices, able to monitor in real time and redundantly both the number of particles and the beam position. Both devices are composed of two wide integral ionisation chambers, two strip chambers each orthogonal to the other, and a pixel ionisation chamber. Due to the very high scientific and technological level involved, the recent clinical utilisation and the scarcity of protons or carbon ions centers, it is necessary to define an accurate physicaldosimetric protocol, propedeutic to the initial clinical activities. In the following paragraph dose delivery commissioning procedures will be described; afterwards, both dosimetric measurements and Montecarlo simulations will be deeply investigated. These last set of activities are needed in order to chacacterise the beams from the physical and dosimetric point of view and will be performed following the experience cumulated in the centers already operating, in particular GSI (Darmstadt, Germany), HIT-DKFZ (Heidelberg, Germany), PSI (Villingen, Switzerland) and NIRS (Chiba, Japan). In paragraph 6, the technical details of the CNAO Medical Physics equipment, dedicated to the high energy beams dosimetry, will be reported. 2 Dose in water under reference condition In case of carbon ions beams, the dose in water under reference condition will be calculated taking into account the contributes of energetic spectra and fluencies of the ions with nuclear charge between Z=1 and Z=6. These ions are originated from projectile nuclear fragmentation. On the other hand, the contribute originating from the neutron fragmentation and target fragmentation can be neglected. For carbon ions beams the formalism used at GSI, introducted by Hartmann et al in 1999, will be adopted at CNAO. It will be employed in order to establish the mean values used to calculate dose, in particular W value and stopping power ratio. More generally, both for protons and carbon ions, the absorbed dose at the effective depth will be calculated as follows: D(z eff ) = M corr * N w * k Q where z eff is the effective measurement point, as described by Jäkel et al. in 2000, M corr is the mean value of at least five consecutive reading of a calibrated ionisation chamber corrected by air density effect, polarity effect and ionic recombination, N w is the calibration factor in terms of Page 3 of 27

4 absorbed dose to water for a dosimeter at a reference beam quality Q 0 (Co-60) and k Q factor to correct for the difference between chamber response from Q 0 to Q. The previous formula is consistent with the IAEA protocol TRS-398 and with the already mentioned Hartmann formalism. In the specific case of carbon ions, another corrective factor of 1.03 will be applied. This factor, coming from the GSI experience, concerns the intercomparison between calorimetric and ionimetric measurements (as published in Brede et al. in 2006) and compensates for the underestimation of W air used in IAEA protocol to determine k Q for carbon ions. The absorbed dose under reference condition will be determined using a Farmer type ionisation chamber connected to a digital electrometer and periodically calibrated in terms of dose in water by secondary standard dosimetry laboratory. The chamber will be placed at the isocenter, in a water or water-equivalent phantom, at 7mm depth that is the initial plateau of the depth dose curve. Dose measurements will be performed irradiating the chamber with mono-energetic beams of ten different energies both for protons and carbon ions. In this way the energy interval will be adequately analyzed. Every measurement will be performed as follows: a fixed number of particles (equivalently Monitor Units) corresponding to 1 Gy at the isocenter, will be delivered in a scanned square field of 5 cm size (homogeneity of ±2,5%). The homogeneity of the delivered field is previously verified irradiating, and then analyzing, a radiochromic film. 3 Dose delivery system: calibration procedure In the previous paragraph the measurement procedure of absorbed dose in water under reference condition has been described. The following step consists in the calibration of the dose delivery system used for the dosimetric monitoring (counts) of the number of particles delivered by the synchrotron as well as for the verification of beam intensity and position. Similarly to what happens for conventional radiotherapy, the calibration of dose delivery system must be carried out in order to accurately deliver online the dose to the patients. The common procedure of monitoring system calibration adopted in conventional radiotherapy with photons and electrons, consists in performing for every available energy and modality, a measure of dose under reference condition for a fixed number of monitor units (MU) delivered by the linear accelerator; then it is possible to calculate the ratio (dose per MU). The last parameter, generally set to 1 (1cGy = 1 MU under reference condition), is implemented in the Treatment Planning Page 4 of 27

5 System (TPS) database, in order to be used in the monitor units calculation for each treatment plan. To set this parameter to 1, it is possible to act directly via software or managing via hardware on the linear accelerator dosimetric cards. For particles beams, an analogue dose delivery calibration procedure is needed. In case of the active scanning method, as implemented at CNAO, the whole procedure becomes more complex due to the high number of available energies (250 both for protons and carbon ions). The big amount of energies would make very long the time of measurements, so it is impossible to perform a separate calibration procedure energy by energy. For this reason the calibration procedure suggested in Jäkel et al. in 2004 and already used at GSI will be used; this procedure in fact is based on the determination of a calibration curve rather than the determination of many calibration factors. Respect to the described common methodologies, in this procedure the calibration is expressed in terms of number of particles (counts)/mu ratio rather than of dose/mu ratio. This approach is justified because, in order to obtain a biological dose distribution, the TPS calculates the number of particles to be delivered for each spot. Dose delivery calibration will be performed using a set of representative energies of the whole energy range; in particular MeV for protons, MeV/u for carbon ions. The calibration factor corresponding to a specific energy E, called CF(E) will be calculated: CF(E) = N/UM D m /(S E(z) * UM) * x * y where D m is dose in water under reference condition, expressed in Gy and measured following the IAEA TRS-398 protocol; S E(z) is the massive stopping power of protons or carbon ions with initial energy E, at measurement point in depth (z axis), expressed in MeV * cm 2 /g; x e y are distances along two axis x and y (expressed in cm, both set to 0,2 cm) between two consecutive spots of dimension (FWHM) of 6 mm. The delivered number of particles is identical for each spot and will be fixed in order to obtain 1 Gy at the isocenter. Even in this context, as already mentioned in the previous chapter, the formulation above is valid assuming that delivered dose under reference condition is homogeneous between ±2,5% (field dimension of 5x5 cm 2 at isocenter). Both for protons and carbon ions, the obtained energy-dependent calibration factors will be interpolated having, as a result, a calibration curve F(E), with CF(E) = k fit * F(E). Page 5 of 27

6 Generally, the parameters in the function F(E) will be kept fixed since curve shape should not vary with time in the assumption that the energy response of dose delivery system is constant; the parameter that could be periodically checked basing on the quality assurance tests on dose delivery system, is the scaling factor (k fit ), initially set to 1. Both the function F(E) and the parameter (k fit ) will be registered, and eventually modified under the responsibility of the medical physicist, in a dedicated software module specific for every beam line. This software will be accessible typing a personal password, through the treatment consolle located in the corresponding control room. 4 Dose in water under non-reference condition and Treatment Planning System (TPS) commissioning The determination of dose in water under non-reference condition, in particular for the clinical practice, will be performed by a dedicated TPS. In order to properly use the software for treatment plans, a preliminary phase of clinical commissioning is absolutely mandatory. The commissioning consists in the implementation of geometrical and physical-dosimetrical particles beams data in the TPS, followed by assessments of the obtained results (depth dose distributions calculated by TPS), comparing to experimental measurements. The TPS used at CNAO is Syngo PT Planning VA11 version, produced by Siemens AG (Germany) that will also provide future software upgrades. The reason of this choice is due to the fact that Siemens software is currently the unique available CE labeled commercial product, able to elaborate treatment plans for protons and carbon ions beams modulated by active scanning. In addition to the typical TPS functionalities (stereotactic localization, DICOM images registration and management (images from computed tomography, magnetic resonance and positron emission tomography), segmentation, inverse planning, calculation and visualization of 3-D dose distribution, calculation of dose volume histogram (DVH) and verification plan), Syngo TPS includes specific functionalities like dose calculation for the raster scan modality and optimisation of biological dose. Since physical-dosimetric data to be implemented into TPS baseline would need a massive set of measurements, an intense use of Monte Carlo simulations that support the experimental data, is certainly unavoidable. As reported in details in this paragraph, the most relevant physical-dosimetric data for protons and ions will concern the depth dose distributions (DDD), the relation between CT-Hounsfield units and water equivalent path length and dose Page 6 of 27

7 transversal profiles. In case of carbon ions beams, other data must be added to the series mentioned before: in particular the fragmentation spectra and stopping powers; for protons beam transversal profiles in air and the proper scaling factors are also needed. As far as RBE (relative biological effectiveness) values is concerned, CNAO will adopt the same approach of GSI and HIT. In fact, the Siemens TPS available in CNAO exploits the potentialities of local effect model (LEM), implemented to convert physical dose into biological dose (for carbon ions beams) and successfully used for several hundred patients treated. Going into detail on the procedures of the TPS commissioning, the first step consists in defining the characteristics that describe proton and carbon ion beams delivered by CNAO accelerator for patient treatment: - List of all beam available energies (expressed in MeV/u), each one corresponds to a defined range in water; - List of all beam available intensities e (number of particles per second) for each energy; - List of all available foci (full width at half-maximum, FWHM, in mm) for each energy. Subsequently, the following physical and dosimetric basic data must be acquired and implemented into the TPS: - Depth dose distributions (DDD) or Bragg curves for each particle type, for every energy and for a single beam size (FWHM of 10 mm), without ripple filter and with every ripple filter configuration (2 and 3 mm thickness, coupled or not, respectively for carbon ions and protons). For every configuration and particle type, at least 20 curves from the representative energy range available must be acquired experimentally in a water phantom with a resolution of some millimeter (in the plateau region and for high energies) up to 0.01 mm (in correspondence of the Bragg peak and for low energies). These measurements will be the experimental reference for extensive Monte Carlo simulations, in particular to perform the fine preliminary adjustment of the physical parameters that would be used in the calculation code. DDD for all the configurations mentioned above will be calculated with Monte Carlo simulations at high spatial resolution. - Transversal dose profiles, measured in a 3-D water phantom with radiocromic films and an array of micro-ionisation chambers, at 20 different depths, for 10 energies (chosen between the 20 energies used for experimental DDD) and for each modality (protons and Page 7 of 27

8 carbon ions). Acquisitions will be done using a beam FWHM of 10 mm and repeated with and without the ripple filter. This kind of measurement is necessary to properly characterize the lateral spread of the thin beam, caused by lateral scattering, which is highly dependent on tissue depth, especially for protons. Limited to carbon ion beams: - Nuclear fragmentation spectrum, calculated by Monte Carlo simulations, for all energies and depths, with and without the ripple filter; - Massive stopping power values in water, calculated by Monte Carlo simulations, for carbon ions and for all the fragmentation products (H, He, Li, Be and B); For proton beams: - Scaling factors, calculated for different materials using Monte Carlo simulations and configured in the TPS database, according to the model proposed and reported by Szymanowsky H et al. in 2002; these factors will be used in the pencil beam calculation model to calculate the proton beam spread in depth and also laterally. - Lateral beam dimensions in air, changing the nominal spot size, measured with radiochromic films and the ionisation chamber matrix, at least at three positions from the nozzle (20, 40 cm and at the isocenter), for the following energies: 70, 100, 150, 200, 250 MeV. Calibration of the Hounsfield Units (HU) of the CT device In the treatment planning step, in order to make a proper use of CT images to calculate dose distributions, it is necessary to determine and configure in the TPS the relation between the HU for a given material and the correspondent water equivalent path length (WEPL), for a defined proton and carbon ion energy, assuming that energy dependence is negligible. This relation has to be determined for all CT tomographs available and for every acquisition and imaging reconstruction protocol (it includes, for example, a pre-fixed voltage applied to the tube, a current and exposition time, a field of view, a reconstruction filter) that it is supposed to be used in clinical practice. For this purpose, at least in the first phase, two different standard imaging protocols have been established: one for the head-neck district and the other for the remaining body areas. For every calibration curve twelve different materials representing the human tissues will be used. Measurements require the use of an appropriate HU phantom, with 17 specific material insert Page 8 of 27

9 locations (bone, air, fat, water, etc.), in the configuration head or body depending on the imaging protocol in study. The procedure of the calibration curve determination is divided in two parts: in the first one, the HU phantom is CT scanned in order to calculate the HU value of every insert, and in the second one, the phantom is irradiated with particle beams of 150 MeV (protons) and 300MeV/u (carbon ions). After the HU phantom CT image acquisition, some ROI of 2 cm diameter are selected inside the material under investigation to calculate the mean HU value inside the ROI. The aim of the second irradiation consists on the measurement of the particles range by using a water column, at first without the HU phantom, to determine the particles range in water r 0, and then interposing the HU phantom in correspondence with the inserts to measure the new range r x. WEPL is defined as follows: WEPL = r a Where r is the difference in the Bragg peak position for the given material and water, and a represents the thickness of the material. By linear interpolation of the measurement points for the materials of interest, the HU calibration curve is obtained and configured in the TPS. 5 Physical and dosimetric equipment A) Pencil beam characterization A1) Bragg curve For the reference Bragg curve measurement, plane-parallel and large area ionization chambers have to be used. Electrodes dimensions of plane-parallel chambers have to be large enough to ensure that all scattered protons produced by multiple Coulomb scattering are detected by the chamber, in other words, to avoid protons lateral scattering outside the chamber (integral dose measurement, fig. 6.1). For proton pencil beam with FWHM up to mm the diameter of the chambers used is 8 cm, whereas a diameter of 4 cm is enough for carbon ions due to the lower lateral scattering. For the Bragg curve measurement the following plane-parallel chambers are required: Page 9 of 27

10 1) Large area Bragg peak chamber, model TM34070 (no waterproof, e.d.=81.6 mm, t window =411 mg/cm 2, 10.5 cm 3 ), to be used as field detector for variable depth measurements in the electronically controlled water phantom PTW MP3-P (Fig. 6.2); it can be used for horizontal and vertical proton and carbon ion beams. 2) Bragg peak chamber, model TM34080 (no waterproof, e.d.=81.6 mm, t window =72 mg/cm 2, 10.5 cm 3 ), to be used as a reference detector. 3) Bragg peak chamber, model TM34073 Roos type (e.d.=39.6 mm, t window =133 mg/cm 2, 2.5 cm 3 ), specific for Bragg curve measurement in the motorized water phantom PTW MP3-P for horizontal carbon ion beams only. All Bragg peak chambers are equipped with specific tools for its use in the motorized water phantom PTW MP3-P. BRAGG PEAK CHAMBER MEASUREMENT Fig. 1 For accurate measurement of the Bragg peak curve, the effective area of the chamber must be large enough with respect to the pencil beam width (FWHM) Pencil beam depth dose curves will be acquired using a motorized water phantom (3D WATER PHANTOM PTW MP3-P), with removable lateral entry window in PMMA (25 cm x 25 cm x 0.5 cm); the phantom can be used both for horizontal and vertical beams. The useful scanning volume is equal to 35 cm x 38 cm x 25 cm, respectively in the transversal direction (A), in the longitudinal direction (C) and in depth (B), according to the horizontal beam direction. Page 10 of 27

11 The motorized arm movement has a minimum translation step of 100 µm in all three scanning directions, and it is possible to use simultaneously 2 plane-parallel Bragg peak chambers. Arm movement can be controlled inside the treatment room by a keyboard or from the control room by dedicated software. Fig. 2 3-D motorized water phantom. Both field and reference Bragg peak chambers are also shown. Standard Bragg curve measurement setup with PTW MP3-P phantom depends on the particle type and beam orientation (horizontal or vertical): 1) Horizontal proton beams Plane-parallel PTW TM34070 chamber (field detector) + plane-parallel PTW TM34080 chamber (reference detector); reference chamber is placed on the outer side of the phantom entry window inside a special holder. In these conditions, the first measurement depth (water equivalent) is approximately 12 mm: this configuration sets a specific limit for ocular protontherapy measurements (E 62 MeV, peak depth 30 mm H 2 O). Page 11 of 27

12 It is advisable to employ a motorized water phantom with a small and thin entry window (20 cm x 20 cm x 0.15 mm PMMA), such as that currently in use in the Catana facility (INFN_LNS). LNS will make this phantom available together with a natural diamond detector PTW mod The latter will be used as a relative detector for depth dose measurements and for the determination of lateral dose profiles in water. 2) Horizontal carbon ion beams No. 2 plane-parallel chambers PTW TM34073, to be used respectively as field detector and reference detector; even in this case, through a special holder, reference chamber is placed in air at the outer side of the lateral entry window. Both chambers (field and reference detectors) are connected to a fast dual-channel electrometer (PTW TANDEM); chambers polarization voltage is independently adjustable for each channel (±0-400 V); the electrometer has a trigger/gate entry to synchronize measurements with external electrical signals. For a correct positioning in water of the effective measurement point of the PTW Bragg peak chambers it is available the PTW TRUFIX positioning system. Data-acquisition and processing is handled by the PTW Mephysto mc 2 dedicated software, which is articulated in three parts: acquisition, analysis and data management. The acquisition module controls chambers movement inside the water phantom and enables the synchronization of the measure with external trigger signals. Mephysto mc 2 software, already in use for conventional beams, has been integrated to be used also for pulsed proton and carbon ions beams produced by a synchrotron (spills). There are two different acquisition modalities for synchrotron pulsed beams: - A trigger signal from the synchrotron to the Tandem electrometer enables the acquisition just during the spill-on times (Spill Start/Stop modality). - An auto-trigger system validates each measurement, it states to exclude the measure from the sampling in case it has been partially or totally carried out during the off beam phase (Spill by time modality). Spill Start/Stop modality needs an external trigger, that is a system that sends to the Tandem electrometer an electrical signal when the spill generated by the synchrotron starts at which the measurement begins. Page 12 of 27

13 There are two ways to synchronize the acquisition, during the rising or falling phase of the synchrotron signal. Number n of spills needed to complete a measurement is set as an input. When the Spill Start/Stop modality is active it is not possible to acquire more points at different depths during the same spill, so the acquisition of ionization curve measurement is slow. There is an input for the spill waiting time (time out), after this time acquisition stops. Trigger input characteristics for the Tandem electrometer have been provided by PTW. In Spill by time modality the Tandem electrometer activates an auto-trigger mechanism that does not need an external system to synchronize the spill-acquisition. In correspondence with the first and the last millisecond of the integration time established for the single measure at a depth z i, the auto-trigger checks whether the measured signal from the electrometer is over a pre-established threshold (radiation level Ξ mgy/min.), generally it is set at the 80% of the mean signal generated by the spill. Measurements that start/stop in the rising/falling of the signal (measurement partially or completely<80%) are not included in the sampling. To ensure that beam radiation is always present during measurements, the measurement time related to the single depth z i has to be smaller than the pause between two consecutive spills. With this modality it is possible to acquire more measurement points during the same spill (the chamber moves in depth during beam irradiation, measurement is faster). Ionization chamber scanning speed in the phantom MP3-P varies from 1 to 50 mm/sec.; the scanning speed does not represent a problem for horizontal beams, because the water displacement due to the chamber movement does not change the measurement depth. For depth dose measurements of vertical beams with a large area Bragg peak camera it is advised to select a low speed value. Analysis of the acquired curves includes the calculation of the most important Bragg curve and modulated beam parameters (FWHM, R max, R 90%, SOBP width, R p, R RES, peak-to-plateau ratio); curves can be compared, it is possible to change the normalization point (to max, to value, to position, to absolute unit) and can be saved in terms of measured charge. Page 13 of 27

14 Depth dose curves can be shifted along the z axis, to take into account the water equivalent thickness ahead of the effective measurement point of the chamber. In order to make a high resolution measurement (10 µm) of the Bragg curve for a pencil beam, a Water Column can be employed. It consists of a water absorber of changing thickness (Peakfinder Water Column PTW T41030). Two thin window PTW Bragg Peak chambers T34080 are placed (Fig. 6.3) externally to the Water Column, in correspondence with the entry surface (IC1, reference chamber) and the exit surface (IC2, field detector); both chambers are connected to a fast dual-channel electrometer (PTW TANDEM). Fig. 3 Picture of the Peakfinder water column. The dual channel electrometer and dedicated control unit are also shown. The water column thickness, and therefore the measuring depth of the IC2 chamber, can be changed by moving the entry window with high precision step-by-step motors; the system is sealed, and can be used with any beam orientation. Chambers integration charge is synchronized with the single spill emission of the synchrotron, thus, for each water column thickness, the net signal is the charge collected by the chambers during the total spill length. Page 14 of 27

15 Measurement depth ranges between 20 and 350 mm. Compared to the PTW MP3-P water phantom, the Peakfinder provides a higher spatial resolution, a shorter depth dose curve acquisition time and, due to the convenience of its set up procedure, it can be used on a daily basis for beam energy check. The software PTW controls the acquisition schemes and processes the reference Bragg curve (FWHM, R max, R 90%, R p, peak-to plateau ratio). A2) Dose transversal profiles For a precise pencil beam characterization dose transversal profiles, as a function of beam energy and scan position, must be measured together with the potential variations introduced by beam modulators along the beam line (range shifters, ripple filters). Pencil beam data must be acquired at different depth along the particle track, with a higher resolution in the Bragg peak region. Radiochromic films will be used as a reference for pencil beam lateral profiles measurement (GSI, PTC), due to their very high spatial resolution ( 100 µm) and energy independence, in particular the EBT/EBT2 model, that shows an effective Z very close to water. The Net Optical Density (NOD) behavior, up to 10 Gy, is mathematically described by a 3 degree polynomial function, with a correlation coefficient close to 1; the curve steepness gradually decreases, with a saturation point after 8 Gy. To work in the higher contrast region, the useful range for dosimetric application is between 0,3 and 3 Gy. For protons, the film response is energy independent in the range between 20 and 260 MeV, meaning that the same calibration curve can be applied for every film irradiation depth. EBT films have been used recently for the commissioning phase of the scanning beam facilities MD Anderson Cancer Center and PTCH. The CNAO standard for EBT film analysis is the Epson 10000XL (A3) color flatbed scanner, using a matrix CCD line sensor. Page 15 of 27

16 For dosimetric applications the film is analyzed in transmission mode; the extraction of the single red channel at 16 bit, from the colour image acquired at 48 bit, allows the determination of the grey level scale. A film holding device (PTW 40040, 265x325 mm²) is available for film positioning on the treatment couch. The holding device includes markers for film positioning with an accuracy of 0.1 mm and can be tilted with respect to the beam central axis. The dosimetric applications are handled via the Film Scan, Film Cal and Film Analysis programs of the PTW Mephysto mc 2 software: 1) Film Scan: for radiographic and radiochromic film scanning; in case of radiochromic films, the automatic extraction of the single red channel is possible. The program provides a correction matrix for the inhomogeneity correction of the response on the scanning bed. 2) Film Cal: for film calibration (O.D., p.v.). 3) Film Analysis: for 1-D and 2-D dosimetric reconstructions. B) Verification of scanned beam dose distributions As for all dynamic techniques, for active scanning systems the dose must be verified in many different points simultaneously. A single ionization chamber is not enough because for each measurement point the whole scanning procedure must be repeated. Scanning system with movable chamber can t be applied because a constant dose rate in every measurement point for the whole irradiation is required. The dose verification standard for scanning beam systems with protons and carbon ions is based on the simultaneous use of multiple ionization chambers. B1) Dose lateral profiles Page 16 of 27

17 Dose lateral profiles will be measured at the isocenter with a linear array of 12 micro-chambers (PTW PinPoint, 0,03 cm 3 ), connected with the multichannel electrometer PTW MULTIDOS with 12 independent channels (fig 6.4). The chamber array (PTW T21004) is fixed on the C arm of the MP3-P phantom by the PTW Linear Detector holder; the measurement length is 250 mm. Fig. 4 Schematic view of the linear array supporting 24 ion chambers The radiochromic film EBT can be use for a better spatial resolution, but taking into account the disadvantage of a delayed reading. For lateral profile measurement of a single pencil beam, real-time scintillation systems could be used, with a sub-millimetric resolution. The system is made of a scintillator (Gadolinium sulfide activated with terbium) positioned, perpendicular to the beam axis, on the exit surface of a water equivalent phantom with variable thickness. The detector is a low noise CCD camera, with a variable integration time ranging from a tenth of a second to some minutes; to protect the CCD, a mylar mirror is positioned behind the scintillator. The PSI experience showed that the light yield is proportional to the dose in the scintillator position, the system could, therefore, be used for relative dosimetry. Page 17 of 27

18 B2) Depth dose profiles (spread-out Bragg peak, SOBP) To verify depth dose profiles obtained with the superposition of many monoenergetic Bragg peaks, cylindrical chambers with a volume lower than 0,1 cm 3 (PTW PinPoint, 0,03 cm 3 ) are used. A volume of 0,03 cm 3 represents the best compromise between the high spatial resolution required and the need of a high intensity signal. Measurements are done in the motorized water phantom PTW MP3-P and a discrete number of points are measured along the SOBP. Opposite to the pencil beam case, for every measurement depth the useful signal is the charge integrated over the whole dynamic sequence. For the verification of a TPS treatment plan SOBP, the dose in the measurement points must be recalculated in water. B3) 2-D Dosimetry Ionization chamber matrices can be considered the ideal instrument for 2-D dosimetry in scanning beam systems thanks to their energy independence and the possibility of a direct response in Gy. The chamber array can be irradiated at different depths by adding water equivalent slabs of different thickness on the detector; the set of measurements, acquired at different depths, represents a 3-D dose reconstruction. The PTW 2-D array XDR is the update of the 2-D array for conventional beams and it was specifically created for proton and carbon ion applications. The array includes 729 flat ionization chambers (5x5x5 mm 3 ), distributed on a 27x27 cm 2 active area, with a distance of 10 mm between two adjacent chamber centers. The ionization chambers are independently calibrated with 60 Co in a SSDL. The sampling time is 400 msec; for active scanning, a threshold for the minimum dose to be integrated can be set in order to remove most of the noise (leakage current) between two consecutive spots. Page 18 of 27

19 The main updates introduced concern the measurement range, adapted to the high dose rates of heavy particle beams (up to 100 Gy/min) and the chamber voltage, increased from 400 to 1000 V; with a distance of 5 mm between the electrodes, polarizing voltages higher than 400 V are required to minimize the effects of ionic recombination for proton and carbon ion beams, where also the initial recombination can be significant. The 2-D array PTW XDR is controlled by: - the control software PTW Matrix Scan - the automatic calibration software PTW Matrix Cal - the data analysis software PTW Verisoft MatrixCal provides two options for matrix calibration: Reference Calibration (relative calibration with a reference matrix). The reference matrix dose values (Mephysto export file.mcc and image file.tiff) are applied for the chamber intercalibration factors correction, with respect to the central one, to obtain a uniform response on the scanning plane. Absolute Calibration For this procedure a reference measurement is needed to obtain the expected dose value in the central chamber position. Only for the central chamber, the measured dose is compared with the absolute value; the remaining chambers calibration factors are corrected with respect to the deviation obtained for the central one. The PTW Verisoft software analyzes and compares calculated dose matrices (from TPS) and measured ones, the gamma function can be evaluated and different calculation criteria, based on measurement point position, can be set (dose value and dose gradient value). The VeriSoft software includes the Merge module for multiple acquisitions management with the 2-D Array system, in order to increase the detector active area from 25% to 100% (4 scanning) and, therefore, the measurement resolution. 2-D ionization chamber arrays are currently used in clinical practice for quality checks and dose distribution verifications in scanning beam facilities (MD Anderson Cancer Center, HIMAC). Page 19 of 27

20 Due to its energy independence, the EBT film could be used for 2D dose distribution verifications; with the simultaneous irradiation of multiple films at different depth, the test provides a 3D verification. The PTW VeriSoft software compares dose matrices calculated from the TPS and measured with radiochromic films. Moreover, a 2D pixel detector called MAESTRO (University and INFN of Firenze) will be used. It represents a good system for pre-treatment 2D dose verification; it s a modular detector based on a monolitical segmented silicon sensor with a n-type implant on a p-type epitaxial layer. The detector thickness is 50 micron, with the addition of a 300 micron framework of Czochralski Silicon. The pixel dimension is 2 mm x 2 mm, with a center to center distance of (pitch) 3 mm. Each module is made of a pixel (6.3 cm x 6.3 cm area). At present, two adjoining modules were assembled, with an overall dimension of 12.6 cm x 6.3 cm. The electronic reading is based on TERA06-type integrated circuits, designed by INFN Torino and distributed by IBA Dosimetry Group. Due to the provided high spatial resolution, the system will be used for beam mapping on transversal planes. B4) 3-D Dosimetry For a 3-D verification of dynamic treatment plans, the 3-D Detector Block (PTW T21003, fig. 6.5) can be used. The system consists of a perspex block which can mount up to 24 PinPoint ion chambers (0,03 cm 3 ) at three different depths, conveniently staggered in order not to shield each other. Page 20 of 27

21 Fig.5 3-D detector block with 24 PinPoint ion chambers The lateral distance between the chambers can be set to 10 or 15 mm, with 3 different measurement depth; the system can be used with horizontal and vertical beams. The detector block can be mounted on one of the PTW MP3-P moving arms, with the possibility of changing the 24 measurement points coordinates from one measurement cycle to the next one. The system requires two 12-channel electrometers (PTW Multidos) for charge reading. For each measurement configuration, the collected charge must be integrated over the whole dynamic sequence delivery. The control software includes chamber positioning, dose measurement and in the next future, the dosimetric comparison with Siemens TPS data. The advantage of the 3-D Detector Block, compared to 2-D Array systems is the simultaneous chamber irradiation at different depths and lateral positions; even if on a limited number of points, this will provide a somewhat 3-D check on the whole scanning procedure. For dose verification with tissue heterogeneities the PTW Inhomogeneity Phantom can be used. The phantom consists (fig6.6) of a half sphere of PMMA of 200 mm diameter, with 11 inserts of 20 mm diameter and 10 mm length, of known density, ranging from g/cm 3 (air) to 9.5 g/cm 3. Page 21 of 27

22 With the addition of the PTW T21005 system, the mounting of up to 24 PinPoint chambers is possible, corresponding to the heterogeneities (fig. 6.7). Fig. 6 Inhomogeneity phantom The phantom can also be fixed to the PTW MP3-P entrance window in order to measure the dose, behind the heterogeneities, with a single chamber. The LNS will provide termoluminescent dosimeters TLD100, micro-cubic type (1x1x1 mm 3 ), to be used as comparison dosimeter. A specific framework for the positioning of the dosimeters will be designed, that could be used for in vivo dosimetry in the future. Fig. 7 The inhomogeneity phantom can be fixed to the water phantom C) Dose Delivery system calibration For the calibration of the dose delivery system a Farmer chamber with graphite walls (PTW 30002, local reference chamber) will be used, calibrated in a SSDL in terms of absorbed dose to water at a reference quality (N D,w 60Co Gy/C). Page 22 of 27

23 Moreover, the chamber is introduced in a specific device containing a sealed Sr 90 source, with a known geometrical position with respect to the chamber; the chamber reading in the radioactive device is a precise reference for the calibration long term stability check. In agreement with the IEC, the Farmer calibration will be checked in the radioactive device before every measurement; the chamber reading must be within 1% of the expected value. In agreement with the GSI protocol for calibration measurements the PTW RW3 slab phantom will be used; a specific slab is provided for the Farmer chamber placement, that allows the positioning of the effective measurement point at the reference depth. The PTW UNIDOS (secondary standard, reference class dosimeter) electrometer will be used for charge reading (nc); both polarization voltage and polarity can be changed (P ion, P pol. ). Moreover, two water phantoms for absolute dosimetry are available, for horizontal beams (T41023, entrance window 170 mm x 170 mm x 3,05 mm) and vertical beams (T41001), equipped with graduated scales. The two phantoms could be used for daily check of the dose delivery system calibration. To verify the reference field homogeneity (5x5 cm 2, as described in paragraph 4), EBT radiochromic films will be used. D) Hounsfield Unit (HU) calibration To take heterogeneities into account, as in conventional RT, where HU are translated in relative electronic densities, for protons and carbon ions they are converted into WEPL (as described in paragraph 5). For radiotherapy planning, an experimental one-to-one relation between HU and WEPL values in different tissues must be defined. A phantom with different heterogeneities, simulating human tissues (from lung to dense bone), is used for HU measurement. Page 23 of 27

24 The phantom used is the Electron Density Reference Phantom (CIRS), made of a body of epoxy material, divided in two sections: a small one ( head phantom) with circular section and a bigger one ( body phantom), with elliptic section, containing the first one. The head unit is characterized by 9 holes of 30,5 mm diameter, while the containing ring is provided by 8 holes. The phantom, in its body version, contains a total of 17 locations for different electronic density materials, ranging from 0,20 g/cm 3 to 4,51 g/cm 3 (titanium). WEPL values for protons and carbon ions (monoenergetic beams) are measured in a water phantom, in terms of range variation due to the heterogeneity compared to range in water, normalized to the insert thickness. WEPL = R water L R insert insert Fig. 8 Example of Bragg peak curves measured in water with and without the insert Range variations with the heterogeneity are measured (fig. 6.8) with large area PTW Bragg Peak chambers, using the PTW MP3-P water phantom or the Water Column PTW Peakfinder. E) Alanin dosimetry (dose determination in water under reference conditions and for dosimetric intercomparison) A dosimetric method, complementary to the ionisation chamber, for dose measurement in water under reference conditions is the alanin/epr system (Electron Paramagnetic Resonance) implemented by the Istituto Superiore di Sanità (ISS). This system is based on the detection of the stable free radicals produced by the ionizing radiation in the alanin aminoacid by means of the electron paramagnetic resonance. Page 24 of 27

25 The free radical concentration, and therefore the intensity of the EPR signal, grows linearly with dose. Conversion of EPR measurements in terms of dose in water is obtained through a calibration curve, that has been created and periodically verified by the primary beam of the Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti (INMRI-ENEA). Dose measurement uncertainty is about 1% (1σ) for dose values up to 10 Gy. For dose determination, alanin dosimeters will be placed at the isocenter in a water or water-equivalent phantom, at the reference depth. Dosimeters that will be used are Gamma service (Leipzig, Germany) products. For EPR measurements an ELEXSYS 500 spectrometer produced by Bruker (Karlsruhe, Germany), operating in the X band (9.2 GHz), will be used. Alanin dosimeters, considering its high precision property, robustness, absence of fading and the possibility of being sent by post, will be used for intercomparison dosimetry between operating Hadrontherapy centers. The aim of the intercomparison, in addition to the verification of the agreement between calculated and measured dose from the same Center, is to provide a tool for validation of the reliability and dose uniformity provided by the different Centers. Measurements relative to dosimetric intercomparison will be carried out reproducing the same experimental setup as that for those measurements under reference conditions. F) Geometric verifications To verify the coordinate systems of imaging devices, with respect to the reference laser system, the cylindrical Positioning (PTW) PMMA phantom will be used, with internal markers. It s a specific phantom for the evaluation of the geometric accuracy of the TPS and all the related imaging systems. It includes 4 metal circles, with small metal spheres in the center, placed on 2 perpendicular planes to get 3-D geometric information. The accuracy is evaluated in terms of size and position of the inserts, with respect to the isocenter, on CT images imported on TPS, on the DRR reconstructed from CT data and on images acquired in the treatment room with the set-up verification system. Page 25 of 27

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