1. IMPORTANT ASPECTS OF TOP IMPLART TECHNOLOGY LUIGI PICARDI – UTAPRAD ENEA Frascati MEDAMI – ALGHERO - 4 Sept 2014

2. The Agency role ENEA is the Italian National Agency for New Technologies, Energy and Sustainable Economic Development Agency's activities are targeted to “research, innovation technology and advanced services in the fields of energy - especially nuclear energy - and sustainable economic development”. The Agency currently operates with about 2700 staff members, on 11 different research Centers, Frascati is the second in size.

3. The ENEA Accelerator Laboratory is in ENEA Frascati Research Centre. It grew up as an extension of the accelerator group that built in the fifties the 1 GeV Frascati Electrosynchrotron, and is indeed housed just in the same old building. Today it is a part of “Application of Radiations” Technical Unit UT APRAD An introduction on Accelerator Development in ENEA 3

4. In late sixties the competences in accelerator physics in Frascati area were split between INFN and CNEN (now ENEA), two big scientific institutions. After the synchrotron shut down in 1974, the expertise which still stayed in ENEA was addressed to the development of electron accelerator for applications in medical and industrial fields. Working together with other laboratories in ENEA expert in Radiobiology and Radiation Metrology and with other italian scientific institutions like National Institute of Health (ISS), IFO, and research Hospitals and Universities, the knowhow in the accelerator field was transferred Small electron accelerators in the years ‘80 – ’90 to an Italian company named HITESYS with the site in Aprilia close to Rome. The company was then able to built a Intra Operative Radiation Therapy (IORT) accelerator named NOVAC7 (the first machine installed in an hospital in 1997) 4

5. IORT: IntraOperative Radiation Therapy More than 80 machines NOVAC and LIAC, have been sold to hospitals in Italy, Europe, and recently USA and in other countries. ENEA is always supporting this company for new developments. NOVAC LIAC (ex NRT) (ex Sordina) In 2001 the company Hitesys split in two companies that last year join together in a new single company named SIT still located in Aprilia that now is producing two models Novac, and LIAC 5

6. 6 In 1993 ENEA joins the Hadrontherapy Collaboration setup by Ugo Amaldi in 1991. From the beginning the problem of very huge and costly hadrontherapy facilities was underlined. The comparison between the performance-raising X-rays radiotherapy to the nevertheless excellent protontherapy was immediately evident. ENEA Accelerator Lab on Protontherapy Protontherapy, and more, hadrontherapy shows high plant costs, and a very late mortage. ENEA coordinated therefore a study on the development of compact accelerators in which two compact synchrotrons, a SC cyclotron and a 3 GHz linear accelerator were studied and compared.

7. Protontherapy Hadrontherapy = proton or ion radio therapy Protontherapy = proton radiotherapy Advantages respect to x-rays radiotherapy: spatial selectivity, conformal therapy, no irradiation after bragg peak Better spare health tissues and organs Bragg peak No irradiation beyond a specific depth

8. DIFFERENCE between the two IMRT with 7 fieldsIMPT with 2 fields Comparison IMRT and IMPT Applying the most advanced X-rays radiotherapy techniques to proton accelerator facilities (IMRT) it is possible to obtain di fotoni a better conformal dose distribution (IMPT). Intensity Modulated Protontherapy: IMPT

9. The TOP Project The linear accelerator design, elaborated in 1996 in cooperation with TERA, CERN and partially supported by INFN-ATER Project was then accepted in 1998 for the TOP (Terapia Oncologica con Protoni) Project of the National Health Institute (ISS) which aimed at developing a design of a compact protontherapy accelerator to be host by an existing oncologycal hospital and to promote ancyllary fields like dosimetry, radiobiology and treatment planning

10. The TOP LINAC Composition: 7 MeV Injector, 425 MHz 20 m long 3 GHz linear accelerator divided in 7 modules and two main sections 2 main outputs: One at 150 MeV for semi deep tumours The second at 200 MeV (depending on the choice) for all tumours

11. The TOP LINAC Modularity: Composed by modules that can be fit to the specific needs of the hospital. The construction can be in phases. The facility can be clinically operative even at mid step. Technical Caracteristichs: Operating RF: 3 GHz -> compactess, well known and cheap technology Pulsed accelerator, naturally suited to IMPT (Intensity Modulated ProtonTherapy)-> XYZ-SCAN High quality beam -> low losses, cheaper magnets National Initiative : Collaboration between italian institutions, specific patents, possible technology transfer to the same companies which are involved in the production of IORT accelerators The system had peculiar characteristics that were considered able to compete circular accelerators for a protontherapy facility

12. The TOP Project and the TOP Linac The TOP Project therefore was the start of a long collaboration in the field of protontherapy between ENEA, ISS (National Institute of Health) Istituto Regina Elena in Rome (IFO) which has been treated as the referent end-user Responsibilities were divided among ENEA (accelerator) ISS (dosimetry, monitoring) and supervisor as to a medical device IFO (clinical requirements, treatment planning, shielding) The practical construction of the accelerator was only partially funded (€2.5 M) by an agreement that lasted 7 years (1998-2005) by which ENEA was able to order a 7 MeV injector and produce beam transport lines and prototypes of the next accelerating structures.

13. Beam spot fuorescent screen dia =20 mm Beam size 2 mm 13 Injector is commercially available accelerator made by AccSys-Hitachi (USA) Modified to produce low current proton pulses. Composed Duoplasmatron source RFQ 3 MeV at 425 MHz DTL up to 7 MeV at 425 MHz Current is delivered in Pulses (20-100 us) Rep rate 0-200 Hz Intensity 0 – 150 uA variable through einzel lens The injector

14. At the end of the TOP Project (2005) the same group of institutes (ENEA, National Institute of Health (ISS) and IFO) asked for specific funding to Regione Lazio to continue the TOP Linac and build a 150 MeV linear accelerator working prototype to be installed at IFO in Rome as a first step of a larger facility. In 2010 an agreement was signed between ENEA, ISS, IFO and Regione Lazio and at the beginning of 2013 the TOP IMPLART Project started with a € 2.5M funding. Recently other €2M have been added The name was slightly changed in TOP IMPLART where IMPLART= Intensity Modulated Proton Linear Accelerator for RadioTherapy It has been funded (by now only high tech) by Regione Lazio with funds addressed to the development of technology for medicine and therefore is intended to be carried on as much as possible with the help of industries operating in Regione Lazio. 14 TOP and TOP IMPLART projects

15. IMPLART-150 15

16. IMPLART-150 16

17. IMPLART-150+ Beam Delivery 17

18. IMPLART-230 18

19. IMPLART-230 + 3 Beam delivery 19

20. TOP IMPLART Layout 20

21. Challenging Performances Pulse rep rate (typ) 100 Hz (max 200 Hz) Typ Charge 3 10 8 – 10 6 protons/pulse Pulse to pulse current variation Fast energy variation (magnet speed limited) Low current losses in the accelerator All require a very good control system and alignment, and a low current on-line measuring system 21

22. Pulse charge variation Pencil beam treatments require 100 – 30000 spots that are reached (max) in 150 sec @200 Hz. This require a change of charge for each pulse with a dynamic range larger than 100: – The Einzel lens after source (pulsed) can provide ( 1:25 ) – The shift of the injector pulse with respect to the RF pulse will provide the rest (1-4 us) (but the jitter has to be kept below 10 ns that corresponds to 1% uncertainty for 1 us pulse) 22

23. 23 Energy variation In order to vary the energy, above 85 MeV it is possible to switch off one or more RF plants, and vary the power on the last powered klystron.

24. Single Output facility with local shielding 24 The low beam losses and the low average energy of the lost particles allow thinking of a locally shielded accelerator, with single output beam, The heavy shielding would only be necessary for the treatment room

25. Space reserved for TOP IMPLART Facility IFO SITE

26. 26 IMPLART-150 Accelerator: Technology The prototype funded by Regione Lazio is in costruction at ENEA Frascati, using a 20 m long bunker that will be extended to 30 m for accommodating the 150 MeV linac

27. 27 The injector is the TOP injector. The TOP IMPLART program has included a vertical output beam to be used for cellular radiobiology The beam is bent upward by a 90° magnet with parallel edges and the beam is diffused to the output kapton window by a gold foil to create an homogeneous distribution The 7 MeV injector and RB Line

28. 28 The 7 -35 MeV part of the LINAC When magnet is off the beam is focused by other two quads to the first of the 4 accelerating SCDTL structures. These will boost the beam up to 35 MeV The fraction of the beam at the SCDTL output will be 10% of the injected

29. DTL (425 MHz) vs SCDTL (3 GHz) SCDTL (patented by ENEA in 1995) comes from the need to compact the size of DTL structures. Protontherapy requires to accelerate a very low current, that for a linac means no space charge problems and allows the use of high frequency operation. On the left the 425 MHz Drift Tube Linac structure and on the right the 3GHz Side Coupled DTL.

30. 30 SCDTL REALIZATION at CECOM SCDTL module 1(up to 11.6 MeV): operating; module 2 and 3 (up to 27 MeV): ready for end of the year Module 1 at CECOM (Guidonia, RM) During construction and tests Inside the accelerating structure PMQ for Focusing Final assembly Cold RF tests before brazing

31. 31 The 35 -150 MeV Part of the Linac The last accelerating and main part of the linac is called CCL after the name of the accelerating structure used. It is divided in 4 modules, each powered by a single RF unit. Each unit will provide a 20 -35 MeV energy jump.

32. 32 CCL structures Several CCL structures have been build in our laboratory and used successfully for electron accelerators. For proton accelerators, both TERA and INFN (Naples) have developed working models at 65 and 30 MeV, the former tested at LNS ADAM, a Cern Spin-off company has also built a CCL module at 30 MeV shown in figure

33. 33 IMPLART-150 Accelerator: Status The TOP IMPLART program has been effectively funded 1.5 year ago. Through this year, collaborations (besides ENEA-ISS and IFO) were setup or strenghtened La Sapienza University in Rome (SBAI Dept) Tor Vergata University in Rome (Industrial engineering Dept Companies, mostly italian: CECOM, NRT R&D, SIT, TSC, ADAM, ITEL

34. 34 Main Results: Accelerator Beam accelerated from the first SCDTL module at the energy of 11.6 MeV: behaviour according to theory. First time in the world that a proton beam is accelerated by a 3 GHz structure while focused in a FODO PMQ lattice. Beam energy measured by range measurement in aluminum. This means: Construction OK A vertical output beam line has been setup with energy 3-7 MeV for cellular radiobiology experiments. Accelerator running every day at 7 or 11.6 MeV

35. 35 Main Results: Beam monitoring (ISS) Monitor, on a single pulse, of the transverse beam profile (x and y projections) Composed by di microstrip ionization chambers array and wide dynamic range electronics (15pC-2.5nC on a single channel) The monitor has been characterized up to now by 3 MeV linac operating in the same lab at ENEA/Frascati In autumn measurements on the 11.6 MeV proton line See Poster By E. Basile

36. 36 Main Results: Cellular Radiobiology ISS-ENEA V79 cells irradiated at 6 MeV after careful dosimetry, with similar results obtained at Legnaro INFN labs, where a standard facility is operating since many years and with which we collaborated for a check of our dosimetry (R.Cherubini) Other tests next month Cell sample holderBeam distribution on EBT3 (diameter 13 mm)

37. 37 Main results: Animal Radiobiology IFO - ENEA While waiting for a proton beam of at least 18-30 MeV to perform irradiation on superficial tumours, animal models have been used for high doses irradiation tests A setup for exposure of new born rodents has been built. And experiments are under way at IFO with X-rays

38. Difficulties of this program Needless to say that this program has always been considered an experimental one and carries with it several uncertainties. Special care has to be put especially in – The RF and timing control system to keep beam stable and provide all the promised features – Alignment to produce low beam losses – Beam monitoring and diagnostics, to control the charge of each spot, that is delivered in a very short pulse (us). The TOP IMPLART plant has always been thought as a prototype. 38

39. Other Similar Programs However the interest of this approach (especially of the industry) is witnessed also by the fact that other two programs similar to TOP IMPLART are ongoing LIGHT by ADAM, (Geneva) that is a CERN spinoff company born upon the push of Ugo Amaldi and recently acquired by AVO Oncotherapy, England ERHA by ITEL (Ruvo di Puglia, Italy) that recently signed also an agreement with INFN. Both companies have exactly our same approach and signed contracts with ENEA for the design of the first part of the linac (SCDTL) and the dynamic simulations of the beam 39

40. TOP IMPLART Time scale For the future a reasonable time schedule is 27 MeV at the beginning of next year and 35 MeV at mid 2015. A milestone has been setup by Regione Lazio for the operation at 30 MeV, that will be verified mid 2015 by an ad-hoc commission. This will possibly lead to more funds (€ 6.5M) to complete the 150 MeV program. One year more to reach a clinical energy (half 2016) Another year to reach 150 MeV. 40

41. 41 Conclusion It is still a long way, however, timescale and good success of this initiative will depend also on cooperation and synergies we will have with other programs and groups, mainly LIGHT and ERHA, which means strong link between the technical reasearch centres, the hospital and the industrial partners. We are trying our best to improve italian technology in this field. Thank you.