IRRADIATION ACTIVITY WITH THE TOP-IMPLART PROTON LINEAR ACCELERATOR Monia Vadrucci - ENEA 16 th June 2017
Abstract A proton linear accelerator devoted to protontherapy application, is under construction in the Particle Accelerators and Medical Applications Laboratory at the ENEA Frascati research center in the framework of the TOP (Terapia Oncologica con Protoni) IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTherapy) project funded by the regional government of Lazio in Italy. The proton linac is composed by a modular sequence of RF linear accelerators designed to reach the energy of 150 MeV. The beam features, particularly useful for very conformal irradiation of tumours in complex anatomical regions, can be likewise translated to other situations. Therefore, during the process of commissioning of the TOP-IMPLART accelerator, the beam has been also made available as a versatile proton source for ancillary experiments in the framework of other projects. Presently, indeed, the maximum TOP-IMPLART beam energy is 35 MeV and this section delivers a 3 usec pulsed beam at maximum repetition frequency of 25 Hz with a variable charge in each pulse in the range 5-100 pc. This beam is used for pilot experiments to simulate cosmic conditions on the ground and PIXE (Particle Induced X-ray Emission) analysis for the determination of elemental composition of archeological and old painting samples. ENEA - Development of particle accelerators and Medical Applications Laboratory, Fusion and Nuclear Security Department, Physical Technologies for Safety and Health Division, Via E. Fermi 45, 00044, Frascati, Rome, Italy E-mail of the corresponding author monia.vadrucci@enea.it 2
Outline Proton Beam Therapy Proton Beam Accelerators for Protontherapy TOP-IMPLART Project TOP-IMPLART Machine TOP-IMPLART Irradiation Activity TOP-IMPLART Future Development 3
Proton Beam Therapy Radiation Therapy Selective cell destruction (cancer) Dose distribution within the target volume No dose out side the target volume 4
Proton Beam Therapy Radiation Therapy Photons Exponential behaviour Protons Low entrance Dose (plateau) Maximum Dose at depth (Bragg peak) Rapid distal Dose fall-off Courtesy of National Cancer Centre of Singapore 5
Proton Beam Accelerators for protontherapy Particle therapy facilities in operation (last update: April 2017) 25 20 15 10 5 0 Austria Canada Czech Republic China England France Germany Italy Japan Poland Russia South Africa South Korea Sweden Switzerland Taiwan USA, CA. www.ptcog.ch/index.php/facilities-in-operation 6
Proton Beam Accelerators for protontherapy Conventional Accelerators types for Protontherapy Cyclotron Synchrotron Synchro-cyclotron Magnetic Field Particle Radius RF frequency Focusing Size Energy Beam pattern Beam Current Fixed / 1-2 T Vary / 1-2 T Fixed / 5-9 T Vary Fixed Vary Fixed Vary Vary Strong Strong Weak Compact Large Compact Fixed Vary Fixed Continuous Beam Pulsed Pulsed High Low Low 7
Proton Beam Accelerators for protontherapy Other Accelerators for Protontherapy FFAG CYCLINAC Dielectric wall accelerators Laser sources FULL LINAC (TOP-IMPLART Project) Titolo della presentazione - luogo - data (piè pagina - vedi istruzioni per visualizzazione in tutta la presentazione) 8
TOP-IMPLART Project Collaboration ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development) ISS (National Institute of Health) IFO (Istituti Fisioterapici Ospedalieri - Regina Elena Institute in Rome) 11 M funded by local Government of Regione Lazio funds addressed to the development of technology for medicine 9
TOP-IMPLART Project Responsibilities Accelerator Dosimetry Monitoring Supervision medical device Clinical requirements Treatment planning Shielding ENEA CR. Frascati (Development of Particle Accelerators and Medical Applications Physical Technologies for Safety and Health Division Fusion and Technologies for Nuclear Safety Department) ISS (Rome) IFO (Rome) 10
TOP-IMPLART Project TOP-IMPLART Terapia Oncologica con Protoni - Intensity Modulated Proton Linear Accelerator for RadioTherapy Objectives Realization of a proton therapy center based on a fully linear proton accelerator 2 main outputs 150 MeV protons to treat semi-deep tumours 230 MeV protons to treat deep tumours 11
TOP-IMPLART Project Layout of the Protontherapy center with 3 treatment rooms 12
TOP-IMPLART Project Layout of the TOP IMPLART accelerator Layout of 150 MeV TOP-IMPLART accelerator under realization, assembly and test at ENEA-Frascati 13
TOP-IMPLART Irradiation Activity TWO beam extraction windows LOW ENERGY VERTICAL LINE (VL) MEDIUM ENERGY HORIZONTAL LINE (HL) 14
TOP-IMPLART Irradiation Activity TWO beam extraction windows RF FREQUENCY 425 MHz Injector (7 MeV) 3 GHz > 7 MeV TOTAL NUMBER OF BEAM LINES 2 VERT. HOR. PROTON BEAM ENERGY (in operation) 3-7 MeV VERT. LINE 18 35 MeV HOR. LINE PROTON BEAM ENERGY (under realization) 41 150 MeV HOR. LINE PROTON BEAM PULSE CURRENT CHARGE PULSE PARTICLE FLUX DOSE RATE 0.1 100 μa 3 7 MeV 0.1 35 μa > 7 MeV 10 nc 3 7 MeV 0.14 nc > 7 MeV 6.25E+10 #/pulse 3 7 MeV 8.75E+08 #/pulse > 7 MeV 0.1 10 Gy/min protontherapy application Up to 100 Gy/min other applications Monitoring and Diagnostic tools - Gafcrhomic HD-V2/EBT3 for beam positioning, size, uniformity and dose measurements Irradiation line VL/HL - Beam current measurements VL/HL - FCT for current stability control HL - Thin ionization chamber for dose setting HL - EPR/Alanine dosimetry HL - MOSFET radiation sensor HL - Semiconductor dosimetry HL - Beam Micro Pattern Ionization Chamber HL VARIABLE PULSE LENGHT 20 100 μs 3 7 MeV 4 μs > 7 MeV REPETITION RATE 10 100 Hz MINIMUM BEAM SPOT 0.2 cm 2 15
TOP-IMPLART Machine It is the first linac running with 3GHz SCDTL (Side Coupled DTL) accelerating modules. Each SCDTL section is powered by a 10 MW peak power klystron tube. The first section, consisting of 4 modules (7 to 35 MeV) has been completed and is operational at low repetition rate (25 Hz). The second section, consisting of other 4 modules (up to 71 MeV), is currently under executive design. The output beam at each stage of the progressive commissioning is fully characterized. The beam is routinely employed in radiobiology experiments and detector evaluation 16
TOP-IMPLART Machine SCDTL # 1 2 3 4 Tanks # 9 7 7 5 Cells/tanks 4 5 6 6 Bore Hole Diameter (mm) 4 4 5 5 Total length (m) 1.11 1.08 1.35 1.11 Output Energy (MeV) 11.6 18 27 35 Status Operative 17
TOP-IMPLART Machine Accelerator Status x= 1.04 mm y= 1.39 mm Beam spot at SCDTL-4 output (exit window) Beam current at SCDTL-4 output on FCT (scale:1 A/mV) 18
TOP-IMPLART Irradiation Activity Variable Energy Output + Variable Pulsed Time Structure + Modularity Of The Linac Many Applications and Different Types of Irradiations Several examples: animal radiobiology proton exposure of biological material for space applications (irradiation in vivo of plants and animals) Proton Induced X-ray Emission spectroscopy (PIXE analysis and PIXE differential of cultural heritage) dose calibration of radiotherapy monitors test of innovative active dosimeters measures of secondary radiation proton induced - passive and active measures of neutron fields development and characterization of passive dosimeters Irradiation line Vertical Horizontal Beam size Experiment description MeV small - Low energy PIXE 3 6 large - Cell irradiation 5 small - High energy PIXE 18 large - Small animals - Vegetables - Dosimeters tests 27 19
TOP-IMPLART Irradiation Activity Variable SET img124.tif point img124.tif Target size - 1 cm of diameter 200 Target position - 5 cm after horizontal linac exit 400 Beam extracted in air Dose distribution at 1 m from the accelerator exit measured on EBT3 film (image resolution 200 dpi): uniformity on samples with 1 cm diameter > 95% 600 200 400 600 800 600 400 200 800 X profile 800 Y profile Dose(cGy) 600 400 200 Dose(cGy) 600 400 200 0 0 200 400 600 800 Distance along profile 0 0 200 400 600 800 Distance along profile 20
TOP-IMPLART Irradiation Activity Variable SET point Target size - 10 cm of diameter Target position - 144 cm after horizontal linac exit Beam extracted in air A special target handling system has been developed: the sample holder is rotated during irradiation to cover the whole target area. The irradiation is done in two steps: in the first step the target is displaced respect to the beam axis of 4.5 cm and in the second step is placed on the beam axis. 21
TOP-IMPLART Irradiation Activity Vertical line irradiation point of the TOP-IMPLART accelerator Low-Energy PIXE setup diagnostic activities with ionizing radiation for the qualitative and quantitative elemental characterization detail with the sample holder and the X rays detector in-vitro radiobiology setup dose-response curves for clonogenic survival in V79 and CHO cells 22
TOP-IMPLART Irradiation Activity Horizontal line irradiation point sof the TOP-IMPLART accelerator 11 MeV setup Vegetables in-vivo sample 18 MeV PIXE setup HB extraction detail with the sample and the X rays detector 23
TOP-IMPLART Irradiation Activity Horizontal line irradiation points of the TOP-IMPLART accelerator 27 MeV setup Vegetables in-vivo sample Target rotation speed= 1 turn in 4 seconds 27 MeV Setup small animals irradiation beam collimator (a), ionization chamber for the dose delivery control (b) mouse holder (c) 24
TOP-IMPLART Irradiation Activity Horizontal line irradiation points of the TOP-IMPLART accelerator MOSFET LiF alanine Si diode Dosimetric characterization of spread beam Current beam parameters Beam current 0.5-35 µa Pulse duration 3.2 µs Pulse repetition frequency 10 Hz Charge/pulse 112 pc (max) Number of particles/pulse 7E8 (max) Number of particles/sec 7E9 (max) Spot area at the beam exit 2 mm 25
TOP-IMPLART Irradiation Activity Horizontal line irradiation points of the TOP-IMPLART accelerator Cathode Front Back 2D ionizing chamber developed as prototype for the dose delivery monitor 26
TOP-IMPLART Irradiation Activity Horizontal line irradiation points of the TOP-IMPLART accelerator Bragg peak in PADC material 27
TOP-IMPLART Irradiation Activity References M. Vadrucci et al., First beam characterization of the TOP-IMPLART proton linear accelerator for cancer radiotherapy, PTCOG 2016 M. Vadrucci, P. Ferrari et al., Preliminary characterization of the neutron field in TOP-IMPLART proton therapy facility, PTCOG 2017 P. Ferrari, M. Vadrucci et al., Preliminary study of neutron field in TOP-IMPLART proton therapy beam, NEUDOS 2017 M. Vadrucci at al., Analysis of Roman Imperial coins by combined PIXE, -XRF and LIBS techniques, TECHNART 2017, Microchemical Journal special issue F. Novelli, M. Vadrucci, L. Picardi, E. Benvenuto, C. Pioli, Effects of in vivo proton irradiation on mouse spleen cells, RAD 2017 Conference Proceedings, vol. 2, 2017 M. Vadrucci et al., A new small-footprint external-beam PIXE facility for cultural heritage applications using pulsed proton beams, accepted for publication on NIM-B 2016 M. Vadrucci et al., The low-energy proton beam for radiobiology experiments at the TOP-IMPLART facility, Biophysics and Bioengineering Letters, vol. 8, no. 1, 2015 M. Vadrucci, et al., Mimicking extreme astrophysical environments: first trials of irradiation of plant tissues with the TOP-IMPLART protontherapy accelerator, Agrospace 2016 M. Vadrucci et al., Diagnostics methods for the medium energy proton beam extracted by the TOP IMPLART linear accelerator, IPAC 2017 E. Cisbani et al., Micro pattern ionization chamber with adaptive amplifiers as dose delivery monitor for therapeutic proton LINAC, IBIC 2016 - ISBN 978-3-95450-177-9 C. De Angelis, A. Ampollini, E. Basile, E. Cisbani, Della Monaca, F. Ghio, R. M. Montereali, L. Picardi, M. Piccinini, C. Placido, C. Ronsivalle, A. Soriani, L. Strigari, E. Trinca, M. Vadrucci, Characterization of a 27 MeV proton beam linear accelerator, NEUDOS 2017 M. Vadrucci et al., Calibration of GafChromic EBT3 for absorbed dose measurements in 5 MeV proton beam and 60Co γ-rays, Med. Phys., vol. 42, no. 8, pp. 4678 84, 2015 M. Vadrucci, et al, Proton irradiations of micro-tom red hairy roots to mimic space conditions, IPAC, p. 2249, 2015 S. Massa et al., Tomato hairy root cultures as a platform for the bioproduction of valuable molecules and as a tool to test extreme astrophysical conditions, Agrospace 2016 28
TOP-IMPLART Future Development Accelerating structures development New proton energies available for new experimental campaigns SCDTL # 5 6 7 8 Tanks # 5 5 3 3 Cells/tanks 7 7 8 8 Bore Hole Diameter (mm) 6 6 6 6 Total length (m) 1.27 1.49 1.07 1.13 Output Energy (MeV) 45 55.5 63 71 Status Under executive design Eye Proton Therapy (uveal melanoma) 29
Acknowledgements & Contancts ENEA Laboratory of Development of Particle Accelerators and Medical Applications A. Ampollini, F. Borgognoni, P. Nenzi, L. Picardi, C. Ronsivalle, V. Surrenti, E. Trinca ENEA Laboratory of Biomedical Technologies M. Balduzzi, C. Marino, F. Novelli, M. M. Rosado, C. Patrono, C. Pioli ENEA Laboratory of Biotechnology E. Benvenuto, E. Bennici A. Desiderio, S. Massa, M.E. Villani ENEA Laboratory of Photonics Micro and Nanostructures Laboratory R.M. Monitereali, M. Piccinini ENEA Laboratory of Radiation Protection Dosimetry L. Campani, P. Ferrari, F. Mariotti INFN-FI LABEC Laboratory M. Chiari, A. Mazzinghi Istituto di Superiore di Sanità C. De Angelis, E. Cisbani, Della Monaca, F. Ghio, C. Placido monia.vadrucci@enea.it vadrucci.monia Italian Space Agency BIOxTREME project Regione Lazio TOP- IMPLART project 30