Few-seconds range verification with short-lived positron emitters in carbon ion therapy.

In-beam PET (Positron Emission Tomography) is one of the most precise techniques for in-vivo range monitoring in hadron therapy. Our objective was to demonstrate the feasibility of a short irradiation run for range verification before a carbon-ion treatment. To do so a PMMA target was irradiated with a 220 MeV/u carbon-ion beam and annihilation coincidences from short-lived positron emitters were acquired after irradiations lasting 0.6 s. The experiments were performed at the synchrotron-based facility CNAO (Italian National Center of Oncological Hadrontherapy) by using the INSIDE in-beam PET detector. The results show that, with 3·107 carbon ions, the reconstructed positron emitting nuclei distribution is in good agreement with the predictions of a detailed FLUKA Monte Carlo study. Moreover, the radio-nuclei production is sufficiently abundant to determine the average ion beam range with a σ of 1 mm with a 6 s measurement of the activity distribution. Since the data were acquired when the beam was off, the proposed rapid calibration method can be applied to hadron beams extracted from accelerators with very different time structures.

Patients With Cancer in the Countries of South-East Europe (the Balkans) Region and Prospective of the Particle Therapy Center: South-East European International Institute for Sustainable Technologies (SEEIIST).

PURPOSE: A recent initiative was launched for establishing the South-East European International Institute for Sustainable Technologies (SEEIIST), which will provide a cutting-edge Hadron radiation therapy treatment and research institute for treating cancer patients with Hadron therapy (HT). To justify the initiative for building the SEEIIST facility, a study was conducted to estimate the number of patients with cancer from the SEE region that would be eligible for HT. METHODS AND MATERIALS: Two different methods for projecting the future annual cancer incidence have been applied: (1) using the International Agency on Research on Cancer@World Health Organization's (WHO) Globocan model which uses country's demographic factors, and (2) averaging the crude incidence data of 3 SEE countries with available national cancer registries, using a linear regression model of combined incidence per 100,000, and applying it to the entire SEE region. Cancer epidemiology data were collected and studied by using the countries' cancer datasheets from WHO. The top 10 cancers were presented for the SEE region. Studies of other countries were used to develop a primordial model for estimating the number of SEE patients who could be treated most successfully with HT upon SEEIIST commissioning in 2030. RESULTS: A model was developed to estimate the number of eligible patients for HT from SEE. It is estimated that 2900 to 3200 patients per year would be eligible for HT in the new SEEIIST facility in 2030. CONCLUSIONS: After commissioning, SEEIIST will initially treat approximately 400 patients per year, progressing toward 1000. Creation of SEEIIST dedicated patient selection criteria will be both necessary and highly challenging.

Sparse proportional re-scanning with hadron beams.

Spot Scanning is a well-established technique to deliver the dose with hadron therapy systems. For many years re-scanning (called also re-painting) has been used to achieve uniform dose distribution in particular for moving organs, although it leads to an increase of the treatment time. Reducing this time is a major focus of present research. In this paper, after reviewing the current re-scanning techniques, sparse proportional re-scanning is defined and applied to 29 proton patient cases for a total of 54 fields. In this technique, only the highest weighted spot in the whole target is visited a number of times that is equal to the number N of re-scans. The number of visits of the beam spot to all remaining spots is scaled down proportionally to their weight. Sparse proportional re-scanning is advantageous especially in volumetric re-scanning. In order to quantify the potential advantages of this technique in terms of treatment time, a reduction factor of the number of scanned spots has been introduced, evaluated and analysed for 54 proton fields. The conclusion is that the reduction factor is a function of N (having values equal to 2.8 ±â€¯0.3 and 3.6 ±â€¯0.4 for N = 5 and N = 12 respectively) and does not depend either on the shape and volume of the target or on the distance between the scanned layers and the spot grid. The same values are approximately valid also for carbon ion treatments.

Oblique raster scanning: an ion dose delivery procedure with variable energy layers.

In ion therapy accelerator complexes the dose is delivered 'actively' by subdividing the target in equal energy layers (EELs), which are scanned by a beam spot visiting in sequence the planned spots, previously defined by the treatment planning system. Synchrotrons-based complexes have three problems: (i) the switching from the energy needed to scan one Equal Energy Layer to the next takes time, an effect that is more relevant for the very short treatment times now often required; (ii) the unavoidable 'ripples' of the quadrupoles and bending magnets currents produce large erratic time variations of the extracted current complicating the dose delivery; (iii) in case of superconducting synchrotrons, it is difficult to rapidly change the magnetic field because of the power dumped in the cold masses. These problems are mitigated in the proposed Qblique Raster Scanning procedure, in which the magnet currents of the beamlines vary in synchrony and a beam spot of continuously varying energy moves at a constant velocity in the beam direction scanning layers that are not perpendicular to it. In this paper it is shown that, even for a 13.5 s irradiation of a 0.5 l target, the B-field rates can be as low as dB/dt = 0.1 T s-1 and that the best procedures to follow 0.5 l moving targets, which combines 3D feedback systems with a five-fold rescanning, can be applied by accelerating in the synchrotron about 1010 carbon ions. ORS can be used in combination with respiratory gating,and is advantageous also for (synchro)cyclotrons-based centres: the variable energy beam can be produced with a slowly rotating absorber and a superconducting energy acceptance beamline/gantry system (with ΔE/E = ±1.5%) can substitute the more expensive beam transport systems which have ten times larger energy acceptance (ΔE/E ⩾ ±15%).

Beam parameters optimization and characterization for a TUrning LInac for Protontherapy.

TULIP (TUrning LInac for Protontherapy) is a novel compact accelerator system for protontherapy mounted on a rotating gantry (Amaldi et al., 2013, 2010, 2009). Its high-energy Linac has the unique property of being able to modulate the beam energy from one pulse to the next, in only a couple of milliseconds. The main purpose of this study is to optimize the properties of the beam exiting the Linac to make them compatible to medical therapy and to characterize their medical physics properties for later implementation in a Treatment Planning System. For this purpose, multi-particle tracking and Monte Carlo (MC) simulations are used to follow the particles through their path up to the treatment isocenter, following the so-called phase-space method. The data compiled includes particle fluences in air and depth-dose curves and provides the basis for a specific model of the TULIP beam.

ENLIGHT: European network for Light ion hadron therapy.

The European Network for Light Ion Hadron Therapy (ENLIGHT) was established in 2002 following various European particle therapy network initiatives during the 1980s and 1990s (e.g. EORTC task group, EULIMA/PIMMS accelerator design). ENLIGHT started its work on major topics related to hadron therapy (HT), such as patient selection, clinical trials, technology, radiobiology, imaging and health economics. It was initiated through CERN and ESTRO and dealt with various disciplines such as (medical) physics and engineering, radiation biology and radiation oncology. ENLIGHT was funded until 2005 through the EC FP5 programme. A regular annual meeting structure was started in 2002 and continues until today bringing together the various disciplines and projects and institutions in the field of HT at different European places for regular exchange of information on best practices and research and development. Starting in 2006 ENLIGHT coordination was continued through CERN in collaboration with ESTRO and other partners involved in HT. Major projects within the EC FP7 programme (2008-2014) were launched for R&D and transnational access (ULICE, ENVISION) and education and training networks (Marie Curie ITNs: PARTNER, ENTERVISION). These projects were instrumental for the strengthening of the field of hadron therapy. With the start of 4 European carbon ion and proton centres and the upcoming numerous European proton therapy centres, the future scope of ENLIGHT will focus on strengthening current and developing European particle therapy research, multidisciplinary education and training and general R&D in technology and biology with annual meetings and a continuously strong CERN support. Collaboration with the European Particle Therapy Network (EPTN) and other similar networks will be pursued.

History of hadron therapy accelerators.

In the last 60 years, hadron therapy has made great advances passing from a stage of pure research to a well-established treatment modality for solid tumours. In this paper the history of hadron therapy accelerators is reviewed, starting from the first cyclotrons used in the thirties for neutron therapy and passing to more modern and flexible machines used nowadays. The technical developments have been accompanied by clinical studies that allowed the selection of the tumours which are more sensitive to this type of radiotherapy. This paper aims at giving a review of the origin and the present status of hadron therapy accelerators, describing the technological basis and the continuous development of this application to medicine of instruments developed for fundamental science. At the end the present challenges are reviewed.

The use of multi-gap resistive plate chambers for in-beam PET in proton and carbon ion therapy.

On-line verification of the delivered dose during proton and carbon ion radiotherapy is currently a very desirable goal for quality assurance of hadron therapy treatment plans. In-beam positron emission tomography (ibPET), which can provide an image of the ß+ activity induced in the patient during irradiation, which in turn is correlated to the range of the ion beam, is one of the modalities for achieving this goal. Application to hadron therapy requires that the scanner geometry be modified from that which is used in nuclear medicine. In particular, PET detectors that allow a sub-nanosecond time-of-flight (TOF) registration of the collinear photons have been proposed. Inclusion of the TOF information in PET data leads to more effective PET sensitivity. Considering the challenges inherent in the ibPET technique, namely limited ß+ activity and the effect of biological washout due to blood flow, TOF-PET technologies are very attractive. In this context, the TERA Foundation is investigating the use of resistive plate chambers (RPC) for an ibPET application because of their excellent timing properties and low cost. In this paper we present a novel compact multi-gap RPC (MRPC) module design and construction method, which considering the large number of modules that would be needed to practically implement a high-sensitivity RPC-PET scanner, could be advantageous. Moreover, we give an overview of the efficiency and timing measurements that have been obtained in the laboratory using such single-gap and multi-gap RPC modules.

CABOTO, a high-gradient linac for hadrontherapy.

The field of hadrontherapy has grown rapidly in recent years. At present the therapeutic beam is provided by a cyclotron or a synchrotron, but neither cyclotrons nor synchrotrons present the best performances for hadrontherapy. The new generation of accelerators for hadrontherapy should allow fast active energy modulation and have a high repetition rate, so that moving organs can be appropriately treated in a reasonable time. In addition, a reduction of the dimensions and cost of the accelerators for hadrontherapy would make the acquisition and operation of a hadrontherapy facility more affordable, which would translate into great benefits for the potential hadrontherapy patients. The 'cyclinac', an accelerator concept that combines a cyclotron with a high-frequency linear accelerator (linac), is a fast-cycling machine specifically conceived to allow for fast active energy modulation. The present paper focuses on CABOTO (CArbon BOoster for Therapy in Oncology), a compact, efficient high-frequency linac that can accelerate C(6+) ions and H2 molecules from 150-410 MeV/u in ∼24 m. The paper presents the latest design of CABOTO and discusses its performances.

European developments in radiotherapy with beams of large radiobiological effectiveness.

This paper reviews the European activities in the field of tumour therapy with beams which have a Radio Biological Effectiveness (RBE) larger than 1. Initially neutron beams have been used. Then charged pions promised better cure rates so that their use was pursued in the framework of the ;Piotron' project at the Paul Scherrer Institute (Switzerland). However both approaches did not meet the expectations and in the 80s the EULIMA project became the flagship of these attempts to improve the effects of the delivery of radiation doses of large RBE with respect to photons, electrons and even protons. The EULIMA ion accelerator was never built and it took more than ten years to see the approval, in Heidelberg and Pavia, of the construction of the HIT and CNAO ;dual' centres for carbon ions and protons. In 2008 they will start treating patients. The developments that brought to these construction projects are described together with the special features of these two facilities. The third European dual centre is being built by Siemens Medical Systems in Marburg, Germany, while other facilities have been approved but not yet fully financed in Wiener Neustadt (Austria), Lyon (France) and Uppsala (Sweden). Finally the collaboration activities of the European Network ENLIGHT are presented together with the recent involvements of European industries in the construction of turn-key dual centres and the development of a new accelerator concept for hadrontherapy, the ;cyclinac'.

Future trends in cancer therapy with particle accelerators.

Hadrontherapy is the radiotherapy technique that uses protons, neutrons or carbon ions. Protons and ions, being, heavy' charged particles, allow a more, conformal' treatment than X-rays and thus spare better the surrounding healthy tissues. By now about 35,000 patients have been treated worldwide with protons and about 1,600 with carbon ions. Since few years protontherapy of deep-seated tumours is booming with two hospital centres running in USA and three under construction. Four centres are treating patients in Japan. The list of constructions going on elsewhere is long: two in China, one in Germany, one in Korea, one in Switzerland. But the future hopes for a qualitatively different radiotherapy are centred on carbon ions: they have a larger biological effectiveness than X-rays and protons and are particularly suited to treat radio resistant tumours, as indicated by the encouraging results obtained on about 1,400 patients in HIMAC (Chiba, Japan) and on about 200 patients at GSI (Darmstadt). Two carbon centres are under construction in Europe: one (designed by GSI) in Heidelberg (Germany) and the other (designed by the TERA Foundation, in collaboration with CERN and INFN) in Pave (Italy). Other projects are moving towards the financing phase in Wiener Neustadt (Austria), Lyon (France) and Stockholm (Sweden). The five European projects are collaborating in the framework of ENLIGHT, the European Network for Light ion Therapy.

CNAO--The Italian Centre for Light-Ion Therapy.

In 1991 the author involved the Italian institute of nuclear physics (INFN) in R&D work in the field of hadrontherapy. In 1992 the TERA Foundation was created with the purpose of forming and employing people fully devoted to the design, promotion and construction of hadrontherapy centres in Italy and in Europe. The present contribution describes the main project of TERA, the CNAO (Centro Nazionale di Adroterapia Oncologica), and the status of its construction in Pavia. The Italian Centre is based on the optimised medical synchrotron designed in the framework of the "Proton Ion Medical Machine Study" (PIMMS) carried out at CERN from 1996 to 2000 with CERN, the Med-AUSTRO project, Oncology 2000 (Prague) and TERA as partners. In the following years TERA introduced modifications and improvements in the original PIMMS design producing what is now dubbed the PIMMS/TERA design. Since 2001 the construction of CNAO has been endorsed by the Italian government to the CNAO Foundation formed by five major hospitals, seated in Milan and Pave, and by TERA. Since 2003 INFN is an Institutional Participant. The site chosen at the beginning of 2003 (37,000 m2) is in the close vicinities of one of the five hospitals, the San Matteo University Hospital of Pave. The construction plan foresees the treatment of the first patient at the end of 2007.