Centro Nazionale Di Adroterapia Oncologica Research Articles

AISHa: an ECRIS for nuclear-physics, new clinical protocols and material experiments

The Advanced Ion Source for Hadrontherapy (AISHa) is an ECR ion source operating at 18 GHz, developed with the aim to produce multiply charged ion beams with low ripple, high stability and reproducibility. Due to its unique peculiarity, it is the most suitable choice for medical applications, but also for nuclear-physics and material experiments. Two sources have been realized: the first at INFN-LNS and the second at the Centro Nazionale di Adroterapia Oncologica (CNAO). The first one, fully commissioned at INFN-LNS, will be used as test-bench for development of new beams and several R&D activities are planned within the IONS experiment to increase plasma confinement and to refine techniques of non-invasive plasma diagnostics to correlate plasma and beam parameters. The second one recently produced the first beam and it will allow to increase the CNAO potential in the field of experimental and industrial research, with the long-term goal of introducing new ionic species into clinical practice such as helium, oxygen and later also iron and lithium, useful for bio-spatial research. In this work, the key peculiarities and the experimental results of the two Aisha ion sources will be presented.

Preliminary tests of Plastic Scintillator Detector for the High Energy cosmic-Radiation Detection (HERD) experiment

The High Energy Cosmic Radiation Detection (HERD) facility, onboard the future China’s Space Station (CSS), will provide high quality data on charged cosmic rays and gamma rays in the energy range from few GeV to PeV. HERD will be equipped with a fine granularity cubic crystals calorimeter and a precision tracker detector. The entire instrument will be surrounded by a Plastic Scintillator Detector (PSD) that will be used to discriminate charged from neutral particles in order to correctly identify gamma-rays and nuclei. One proposed configuration for the HERD PSD consists of tiles of plastic scintillator, optically coupled to SiPMs. In 2019-2020, two beam tests were performed at CNAO (Centro Nazionale di Adroterapia Oncologica) in Pavia (Italy), exposing some PSD tiles, equipped with SiPMs, to low-beta p and C ion beams in order to evaluate the detector response to heavy ions. Spatial and temporal resolution were also evaluated using a radioactive source.

The AISHa ion source at INFN-LNS

The Advanced Ion Source for Hadrontherapy (AISHa) is an ECR ion source operating at 18 GHz, developed with the aim of producing high intensity and low emittance highly charged ion beams for hadrontherapy purposes. Due to its unique peculiarities, AISHa is a suitable choice for industrial and scientific applications. In the framework of the INSpIRIT and IRPT projects, in collaboration with Centro Nazionale di Adroterapia Oncologica (CNAO), new candidates for cancer treatment (including metal ion beams) are being developed. Moreover, within the IONS experiment, AISHa will be the test-bench for the development of an innovative active plasma chamber designed to increase plasma confinement by changing plasma fluxes. OES technique will be also used to refine techniques of non-invasive plasma diagnostics. Finally, a dedicated setup is under realization to provide impinging beams and detection systems for target production in nuclear physics experiments.

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.

Thin low-gain avalanche detectors for particle therapy applications

The University of Torino (UniTO) and the National Institute for Nuclear Physics (INFN-TO) are investigating the use of Ultra Fast Silicon Detectors (UFSD) for beam monitoring in radiobiological experiments with therapeutic proton beams. The single particle identification approach of solid state detectors aims at increasing the sensitivity and reducing the response time of the conventional monitoring devices, based on gas detectors. Two prototype systems are being developed to count the number of beam particles and to measure the beam energy with time-of-flight (ToF) techniques. The clinically driven precision (< 1%) in the number of particles delivered and the uncertainty < 1 mm in the depth of penetration (range) in radiobiological experiments (up to 108 protons/s fluxes) are the goals to be pursued. The future translation into clinics would allow the implementation of faster and more accurate treatment modalities, nowadays prevented by the limits of state-of-the-art beam monitors. The experimental results performed with clinical proton beams at CNAO (Centro Nazionale di Adroterapia Oncologica, Pavia) and CPT (Centro di Protonterapia, Trento) showed a counting inefficiency <2% up to 100 MHz/cm2, and a deviation of few hundreds of keV of measured beam energies with respect to nominal ones. The progresses of the project are reported.

Accuracy assessment of the CNAO dose delivery system in the initial period of clinical activity and impact of later improvements on delivered dose distributions.

A retrospective analysis of the dose delivery system (DDS) performances of the initial clinical operation at CNAO (Centro Nazionale di Adroterapia Oncologica) is reported, and compared with the dose delivery accuracy following the implementation of a position feedback control. Log files and raw data of the DDS were analyzed for every field of patients treated with protons and carbon ions between January 2012 and April 2013 (~3800 fields). To investigate the DDS accuracy, the spot positions and the number of particles per spot measured by the DDS and prescribed by the treatment planning system were compared for each field. The impact of deviations on dose distributions was studied by comparing, through the gamma-index method, 2 three-dimensional (3D) physical dose maps (one for prescribed, one for measured data), generated by a validated dose computation software. The maximum gamma and the percentage of points with gamma≤1 (passing volume) were studied as a function of the treatment day, and correlated with the deviations from the prescription in the measured number of particles and spot positions. Finally, delivered dose distributions of same treatment plans were compared before and after the implementation of a feedback algorithm for the correction of small position deviations, to study the effect on the delivery quality. A double comparison of prescribed and measured 3D maps, before and after feedback implementation, is reported and studied for a representative treatment delivered in 2012, redelivered on a polymethyl methacrylate (PMMA) block in 2018. Systematic deviations of spot positions, mainly due to beam lateral offsets, were always found within 1.5mm, with the exception of the initial clinical period. The number of particles was very stable, as possible deviations are exclusively related to the quantization error in the conversion from monitor counts to particles. For the chosen representative patient treatment, the gamma-index evaluation of prescribed and measured dose maps, before and after feedback implementation, showed a higher variability of maximum gamma for the 2012 irradiation, with respect to the reirradiation of 2018. However, the 2012 passing volume is >99.8% for the sum of all fields, which is comparable to the value of 2018, with the exception of one day with 98.2% passing volume, probably related to an instability of the accelerating system. A detailed retrospective analysis of the DDS performances in the initial period of CNAO clinical activity is reported. The spot position deviations are referable to beam lateral offset fluctuations, while almost no deviation was found in the number of particles. The impact of deviations on dose distributions showed that the position feedback implementation and the increased beam control capability acquired after the first years of clinical experience led to an evident improvement in the DDS stability, evaluated in terms of gamma-index as a measure of the impact on dose distributions. However, the clinical effect of the maximum gamma variability found in the 2012 representative irradiation is mitigated by averaging along the number of fractions, and the high percentage of passing volumes confirmed the accuracy of the delivery even before the feedback implementation.

FRoG-A New Calculation Engine for Clinical Investigations with Proton and Carbon Ion Beams at CNAO.

A fast and accurate dose calculation engine for hadrontherapy is critical for both routine clinical and advanced research applications. FRoG is a graphics processing unit (GPU)-based forward calculation tool developed at CNAO (Centro Nazionale di Adroterapia Oncologica) and at HIT (Heidelberg Ion Beam Therapy Center) for fast and accurate calculation of both physical and biological dose. FRoG calculation engine adopts a triple Gaussian parameterization for the description of the lateral dose distribution. FRoG provides dose, dose-averaged linear energy transfer, and biological dose-maps, -profiles, and -volume-histograms. For the benchmark of the FRoG calculation engine, using the clinical settings available at CNAO, spread-out Bragg peaks (SOBPs) and patient cases for both proton and carbon ion beams have been calculated and compared against FLUKA Monte Carlo (MC) predictions. In addition, FRoG patient-specific quality assurance (QA) has been performed for twenty-five proton and carbon ion fields. As a result, for protons, biological dose values, using a relative biological effectiveness (RBE) of 1.1, agree on average with MC within ~1% for both SOBPs and patient plans. For carbon ions, RBE-weighted dose (DRBE) agreement against FLUKA is within ~2.5% for the studied SOBPs and patient plans. Both MKM (Microdosimetric Kinetic Model) and LEM (Local Effect Model) DRBE are implemented and tested in FRoG to support the NIRS (National Institute of Radiological Sciences)-based to LEM-based biological dose conversion. FRoG matched the measured QA dosimetric data within ~2.0% for both particle species. The typical calculation times for patients ranged from roughly 1 to 4 min for proton beams and 3 to 6 min for carbon ions on a NVIDIA® GeForce® GTX 1080 Ti. This works demonstrates FRoG’s potential to bolster clinical activity with proton and carbon ion beams at CNAO.

Abstract ID: 51 Monte Carlo optimization of a neutron beam from 5 MeV 9Be(p,n) 9B reaction for clinical BNCT

Boron Neutron Capture Therapy (BNCT) is an experimental radiotherapy that uses the combination of neutron irradiation and 10B to treat neoplasms. By means of this technique, many clinical trials were performed worldwide with promising results [1] using research nuclear reactors as neutron sources. Anyhow, these machines have several problems that hinder the development of dedicated BNCT hospitals. This issue can now be overcome by using intense-current proton accelerators, which coupled with beryllium or lithium targets yield more than 1014 neutron per second. This can be a boost to BNCT because accelerators are more compact and can be installed within hospitals. The Italian National Institute of Nuclear Physics (INFN) designed and manufactured a Radiofrequency Quadrupole proton accelerator (RFQ) [2] , which delivers 5 MeV protons with 30 mA current in a Continuous Wave (CW) mode and it is coupled to a beryllium target. This accelerator could be installed at Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia. In this work we present the MC calculations for the tailoring of a BNCT neutron beam obtained by the described RFQ. Firstly, we show that MC transport codes such as MCNP and PHITS are not able to simulate the correct neutron spectra from 5 MeV protons interacting on beryllium. Therefore, the neutron double differential source implemented in MCNP was extracted from the measurements performed by Agosteo et al. [3] . As the energy range goes up to 3.5 MeV, neutrons need to be moderated and collimated by a Beam Shaping Assembly (BSA), because BNCT requires a spectrum peaked between 1 and 10 keV. Differently from the past, where the optimal configuration was chosen according to physical characteristics of the beam, in this case the results were evaluated on the basis of the dosimetry obtained in a real clinical case by treatment planning simulation. What emerges, is that the classical figures of merit employed for the tailoring of a clinical BNCT [4] should be taken as a first guideline, while the dosimetric assessment on realistic clinical scenarios is the most appropriate criterion for beam evaluations.

Electrostatic pickup in the CNAO Injection Line

The paper is about the electrostatic pickup installed in the Medium Energy Beam Transfer (MEBT) line of the CNAO (Centro Nazionale di Adroterapia Oncologica), the Italian facility for oncological hadrontherapy. The MEBT Pickup (PUB) has been designed with the purpose of having a continuous and non-interceptive measurement of the horizontal and vertical beam position, close upstream the injection point in the synchrotron. Detector commissioning, data-analysis algorithm and first year measurements are discussed in the paper.

Translational research in radiobiology in the framework of France HADRON national collaboration

France HADRON is a French national collaboration that brings together 26 teams in nine different French cities (Lyon, Caen, Clermont-Ferrand, Paris-Orsay, Nice, Toulouse, Marseille, Strasbourg and Grenoble). This infrastructure was created in 2013 and follows the ETOILE and ARCHADE projects; it is presently funded by public money. Ten teams, from different scientific background, using a wide range of approaches, participate in radiobiology researches upon protons and carbon ion therapy in comparison with photons used in classical radiation oncology. These approaches combine the use of multiple biological models of radioresistant tumors and healthy tissue critical for treatment tolerance. Thus, the determinants of the radioresistance of head and neck squamous cell carcinoma (HNSSC), high-grade gliomas, sarcomas including chondrosarcomas and the ubiquitous endothelial cells and fibroblasts are studied. Multiple methodological approaches are implemented. In particular, these include: the extraction of tumor stem cell populations and their radiobiological comparison with the differentiated tumor cells; the studies in hypoxic and normoxic conditions; the development and the use of models of 3D cell cultures that highlight important differences in cell behaviors; the cell biology with the analysis of typical neoplastic mechanisms such as invasive and cell migration processes, as well as late recovery of irradiated tumor cells that reenter proliferation; the molecular biochemistry with analysis of resistance signaling pathways, telomerase regulation and genomic analysis of predictors of radioresistance in retrospective and prospective series of patients (gliomas, HNSSC, sarcomas) and finally the oxidative stress, genotoxicity and inflammatory measurements in normal human cells at early and late times after irradiation. This work allows a better understanding of the mechanisms of cellular and tumor radioresistance, normal tissue toxicity, but they also enable pre-clinical and clinical approaches. Thus, experimental approaches of combinations of pharmacological treatments acting on the identified resistance or toxicity mechanisms with the different types of radiation studied are developed. The comparison between stem cells and differentiated cells is very interesting in this respect. This information, combined with phenomenological data on survival and relative biological effectiveness (RBE), contributes to the adjustment and parameterization of bio-mathematical predictive models of the cellular response such as the Nanox ® model. This work enables, on the one hand, to suggest hypotheses of clinical trials aimed at acting on tumor radioresistance; and, on the other hand, to integrate into studies associated with prospective transnational clinical research protocols, comparing carbontherapy vs. photon or proton radiotherapy, in collaboration with the European carbontherapy centers, in particular the Heidelberg Ion Therapy (HIT) in Germany and Centro Nazionale di Adroterapia Oncologica (CNAO) in Italy. The potential of France HADRON in radiobiology is important and can make a useful contribution to this field of research, in particular by pursuing a convergence approach of the methods, the models and the topics investigated

Dosimetric characterization of a commercial 2-D scintillation detector for quality assurance tests in scanned proton and carbon ion beams

Introduction Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully and periodically checked to guarantee patient safety. Radiochromic films are used within daily QA checks. Purpose This study aimed at characterizing the Lynx PT system (IBA Dosimetry) and assessing its suitability for QA tests, for proton and carbon ion beams. Materials and methods The Lynx PT is a 2D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. A dedicated software is used for image acquisition, raw data correction and fast data analysis. Lynx was characterized in terms of short-term stability, image geometrical distortion, uniformity, signal proportionality, response dependence on IRIS and on particle intensity, particle energy and type. Irradiations were performed at the Centro Nazionale di Adroterapia Oncologica (CNAO) for both protons and carbon ions. Measurements with Lynx were compared to those made with EBT3 reference films. The detector response dependence on radiation LET was also investigated. Results Lynx basic characterization results have shown a proportional behavior with delivered number of particles. Strong dependence of the acquired signal on beam energy and particle type was found. No significant differences in the investigated beam parameters measured with Lynx and EBT3 film were observed. The detector also showed good performances in term of image uniformity and geometrical distortion. Conclusion The Lynx PT system appears as a promising tool for measurements for both single pencil beam and scanned beam, enabling fast QA and beam optics optimization checks.

Proton beam radiotherapy: report of the first patient treated at the Centro Nazionale di Adroterapia Oncologica (CNAO) [National Center of Oncologic Hadron Therapy

Proton beam radiotherapy, an innovative treatment modality, allows delivery of high radiation doses to the target while sparing surrounding healthy structures. The Centro Nazionale di Adroterapia Oncologica (CNAO), equipped with a synchrotron and capable of using both protons and ions, initiated its clinical activity in September 2011. The first treatment of a skull base tumor with protons is reported here. The case of a 26-year-old man with an intracranial low-grade chondrosarcoma of the right petroclival junction is discussed with emphasis on technical and clinical details. Two previous surgical interventions had achieved partial removal of the tumor and the patient was treated with protons for residual disease. The prescribed dose was 70 GyE in 35 fractions of 2 GyE. Treatment was completed with minimal acute toxicity consisting of grade 1 alopecia and nausea. Nine months after treatment the disease is locally controlled. Use of high-energy protons at CNAO is a safe and effective means of treating a tumor located near critical normal structures.

Monte Carlo Calculations Supporting Patient Plan Verification in Proton Therapy.

Patient’s treatment plan verification covers substantial amount of the quality assurance (QA) resources; this is especially true for Intensity-Modulated Proton Therapy (IMPT). The use of Monte Carlo (MC) simulations in supporting QA has been widely discussed, and several methods have been proposed. In this paper, we studied an alternative approach from the one being currently applied clinically at Centro Nazionale di Adroterapia Oncologica (CNAO). We reanalyzed the previously published data (Molinelli et al. (1)), where 9 patient plans were investigated in which the warning QA threshold of 3% mean dose deviation was crossed. The possibility that these differences between measurement and calculated dose were related to dose modeling (Treatment Planning Systems (TPS) vs. MC), limitations on dose delivery system, or detectors mispositioning was originally explored, but other factors, such as the geometric description of the detectors, were not ruled out. For the purpose of this work, we compared ionization chambers’ measurements with different MC simulation results. It was also studied that some physical effects were introduced by this new approach, for example, inter-detector interference and the delta ray thresholds. The simulations accounting for a detailed geometry typically are superior (statistical difference – p-value around 0.01) to most of the MC simulations used at CNAO (only inferior to the shift approach used). No real improvement was observed in reducing the current delta ray threshold used (100 keV), and no significant interference between ion chambers in the phantom were detected (p-value 0.81). In conclusion, it was observed that the detailed geometrical description improves the agreement between measurement and MC calculations in some cases. But in other cases, position uncertainty represents the dominant uncertainty. The inter-chamber disturbance was not detected for the therapeutic protons energies, and the results from the current delta threshold are acceptable for MC simulations in IMPT.

In-beam PET data characterization with the large area DoPET prototype

Range verification with in-beam PET techniques is a powerful tool for monitoring the correctness of dose delivery in particle therapy. Among the major limitations of in-beam PET systems are the limited detectors size due to the constrained space in which they can be placed to allow the irradiation, and the necessity of a high read-out modularization, due to high activity rates during the irradiation. In this work we present the data acquired at the CNAO (Centro Nazionale di Adroterapia Oncologica) treatment center in Pavia, Italy, with the new DoPET system, specifically designed to operate in in-beam conditions. The new prototype consists of two planar 15cm × 15cm LYSO-based detectors, read out by 9 PMT detector modules each. In particular, we test the capability of our system to determine particle range in various irradiation conditions. Several plastic phantoms were irradiated at the CNAO treatment centre with protons and carbon ions of various energies. The used dose in treatment plans is 2 Gy and the monitoring feedback is produced in a few minutes after the end of the treatment.

Geant4 simulation for a study of a possible use of carbon ion pencil beams for the treatment of ocular melanomas with the active scanning system at CNAO

The aim of this work was to study a possible use of carbon ion pencil beams (delivered with active scanning modality) for the treatment of ocular melanomas at the Centro Nazionale di Adroterapia Oncologica (CNAO). The promising aspect of carbon ions radiotherapy for the treatment of this disease lies in its superior relative radio-biological effectiveness (RBE). The Monte Carlo (MC) Geant4 10.00 toolkit was used to simulate the complete CNAO extraction beamline, with the active and passive components along it. A human eye modeled detector, including a realistic target tumor volume, was used as target. Cross check with previous studies at CNAO using protons allowed comparisons on possible benefits on using such a technique with respect to proton beams. Experimental data on proton and carbon ion beams transverse distributions were used to validate the simulation.

On the parametrization of lateral dose profiles in proton radiation therapy

PurposeThe accurate evaluation of the lateral dose profile is an important issue in the field of proton radiation therapy. The beam spread, due to Multiple Coulomb Scattering (MCS), is described by the Molière's theory. To take into account also the contribution of nuclear interactions, modern Treatment Planning Systems (TPSs) generally approximate the dose profiles by a sum of Gaussian functions. In this paper we have compared different parametrizations for the lateral dose profile of protons in water for therapeutical energies: the goal is to improve the performances of the actual treatment planning. MethodsWe have simulated typical dose profiles at the CNAO (Centro Nazionale di Adroterapia Oncologica) beamline with the FLUKA code and validated them with data taken at CNAO considering different energies and depths. We then performed best fits of the lateral dose profiles for different functions using ROOT and MINUIT. ResultsThe accuracy of the best fits was analyzed by evaluating the reduced χ2, the number of free parameters of the functions and the calculation time. The best results were obtained with the triple Gaussian and double Gaussian Lorentz–Cauchy functions which have 6 parameters, but good results were also obtained with the so called Gauss–Rutherford function which has only 4 parameters. ConclusionsThe comparison of the studied functions with accurate and validated Monte Carlo calculations and with experimental data from CNAO lead us to propose an original parametrization, the Gauss–Rutherford function, to describe the lateral dose profiles of proton beams.

Scan path optimization with/without clustering for active beam delivery in charged particle therapy

PurposeTo compare different algorithms to optimize the scanning path in charged particle therapy with quasidiscrete scanning. We implemented a Hybrid Genetic Algorithm with Heuristics (HyGA) and combined it with clustering techniques. The performance was compared to Simulated Annealing (SA) and to commercially available treatment planning system (TPS). MethodsPerformance and clinical implications were assessed using data from 10 patients treated at CNAO (Centro Nazionale di Adroterapia Oncologica). Clinical treatments are performed relying on beam deflection, avoiding irradiation for transitions between adjacent spots larger than 2 cm. A clustering method was implemented with HyGA (HyGA_Cl), which assumes beam deflection during transition between clusters. Clinical performance was determined as the total number of particles delivered during spot transitions and the number of particles wasted due to beam deflection. Results were compared to scan paths obtained with CNAO TPS. ResultsSA and HyGA produced on average shorter paths compared to the currently available TPS. This did not result in a reduction of transit particles, due to the concomitant effect of beam deflection out of the extraction line. HyGA_Cl achieved 2% average reduction in transit particles when compared to CNAO TPS. As a drawback, wasted particles increased, due to more frequent use of beam deflection. Both the SA and HyGA algorithms reduced the number of wasted particles. ConclusionSA and HyGA proved to be the most cost-effective methods in reducing wasted particles, with benefits in terms of shorter scan paths. A decrease in transit particles delivered with beam deflection can be achieved using HyGA_Cl.

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

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. 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. 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. 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.

SU-E-T-107: Development of a GPU-Based Dose Delivery System for Adaptive Pencil Beam Scanning

Purpose: A description of a GPU-based dose delivery system (G-DDS) to integrate a fast forward planning implementing in real-time the prescribed sequence of pencil beams. The system, which is under development, is designed to evaluate the dose distribution deviations due to range variations and interplay effects affecting mobile tumors treatments. Methods: The Dose Delivery System (DDS) in use at the Italian Centro Nazionale di Adroterapia Oncologica (CNAO), is the starting point for the presented system. A fast and partial forward planning (FP) tool has been developed to evaluate in few seconds the delivered dose distributions using the DDS data (on-line measurements of spot properties, i.e. number of particles and positions). The computation is performed during the intervals between synchrotron spills and, made available at the end of each spill. In the interval between two spills, the G-DDS will evaluate the delivered dose distributions taking into account the real-time target positions measured by a tracking system. The sequence of prescribed pencil beams for the following spill will be adapted taking into account the variations with respect to the original plan due to the target motion. In order to speed up the computation required to modify pencil beams distribution (up to 400more » times has been reached), the Graphics Processing Units (GPUs) and advanced Field Programmable Gate Arrays (FPGAs) are used. Results: An existing offline forward planning is going to be optimized for the CUDA architecture: the gain in time will be presented. The preliminary performances of the developed GPU-based FP algorithms will be shown. Conclusion: A prototype of a GPU-based dose delivery system is under development and will be presented. The system workflow will be illustrated together with the approach adopted to integrate the three main systems, i.e. CNAO dose delivery system, fast forward planning, and tumor tracking system.« less

Proton beam radiotherapy: report of the first ten patients treated at the “Centro Nazionale di Adroterapia Oncologica (CNAO)” for skull base and spine tumours

The Italian National Centre for Oncological Hadrontherapy (Centro Nazionale di Adroterapia Oncologica, CNAO), equipped with a proton and ion synchrotron, started clinical activity in September 2011. The clinical and technical characteristics of the first ten proton beam radiotherapy treatments are reported. Ten patients, six males and four females (age range 27-73 years, median 55.5), were treated with proton beam radiotherapy. After one to two surgical procedures, seven patients received a histological diagnosis of chordoma (of the skull base in three cases, the cervical spine in one case and the sacrum in three cases) and three of low-grade chondrosarcoma (skull base). Prescribed doses were 74 GyE for chordoma and 70 GyE for chondrosarcoma at 2 GyE/fraction delivered 5 days per week. Treatment was well tolerated without toxicity-related interruptions. The maximal acute toxicity was grade 2, with oropharyngeal mucositis, nausea and vomiting for the skull base tumours, and grade 2 dermatitis for the sacral tumours. After 6-12 months of follow-up, no patient developed tumour progression. The analysis of the first ten patients treated with proton therapy at CNAO showed that this treatment was feasible and safe. Currently, patient accrual into these as well as other approved protocols is continuing, and a longer follow-up period is needed to assess tumour control and late toxicity.