Particle Therapy- Why?

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2 Particle Therapy- Why? Kill tumour without affecting healthy cells X-Ray Therapy Head, neck, Spinal cord Eyes, orbits Pelvis Prostate Lung PEDIATRIC Proton Therapy Photon IMRT Photon Proton (Courtesy of IBA) Manjit Dosanjh 2

3 First patient in Europe in 1957 Uppsala, Sweden The Gustaf Werner Cyclotrone First treatment of a patient was performed in November 1957 a woman with cervix cancer. Börje Larsson and Stig Stensson During no patients were treated due to re-buldings Manjit Dosanjh 3

4 Uppsala 1957 The modified synchrocyclotron Bőrje Larsson On the Application of a 185 MeV Proton Beam to Experimental Cancer Therapy and Neurosurgery: a Biophysical Study Doctoral dissertation Alignment system for the treatment with 185 MeV protons ( ) Mexico City 1 U. Amaldi 4

5 Continued proton treatment in Uppsala First treatment of eye melanoma in April 1989 (72 MeV beam with 54,5 Gy in four fractions) Arterio venous malformation, AMV Uveal melanomas and meningeomas in the brain (1991..) (100 MeV beam with 20 Gy in two fractions) Manjit Dosanjh 5

6 Prostate treatment started late 2002 by using a new special platform In 2008 The Swedish Childhood Cancer Foundation funded an adjustable treatment coach for children Manjit Dosanjh 6

7 3 crucial years In the years the rate of progress changed: 1992 at Loma Linda first proton patient 1993 MGH orders the first commercial protontherapy centre 1993 GSI starts the carbon ion pilot project 1994 HIMAC first carbon ion patient Manjit Dosanjh 7

8 Proton therapy is booming Manjit Dosanjh 8

9 Proton facilities in Europe GWI (Sweden) TSL (Sweden) Douglas, Clatterbridge, U.K UCL, Louvain, Belgium CAL, Nice, France 1991 CPO, Orsay, France 1991 PSI, Villigen, Switzerland 1996 HMI, Berlin, Germany Manjit Dosanjh 9

10 Why Heavier Charged Particle Beams? Precision Therapy Conformed to Tumour Sparing of Normal Tissues Increased DNA Damage in Tumor Increased Effect on Hypoxic Tumors Less Repair of Sub-lethal and Potentially Lethal Damage in Cell Cycle Short Overall Treatment Course Use of Radioactive Beam Component for Treatment Verification in beam PET

11 Ultimate Goal: Heavy Ions & Therapeutic Gain Overcoming tumor radioresistance Enhancing tumor cell killing Protecting normal cells

12 Relative Biological Effectiveness (reference vs test radiation) D x = RBE D i

13 Radio Biological Effect : RBE RBE varies not only with type of radiation but also with type of cell or tissue, biological effect under investigation, dose rate and fractionation. In general RBE increases with LET to reach a maximum RBE of 3 to 8 (dependent of the level of cell kill) at LET 200 kevµm and then decreases. An increase in the RBE in itself offers no therapeutic advantage unless there is a differential effect making the RBE for normal tissue smaller than that for the tumour, increasing the relative level of tumour cell killing and the therapeutic ratio. Manjit Dosanjh 13

14 RBE and how does it vary Varies with type of radiation Varies with type of cell/tissue Varies with the biological effect under investigation Varies with dose rate and fractionation An increase in RBE in itself does not offer therapeutic advantage unless there is differential effect between normal and tumour tissues OER (oxygen enrichment ratio) effects RBE Effected by presence of other chemicals present

15 Carbon ion treatment in Europe Carbon ion treatments of patients at the GSI started in 1997 mostly head-and-neck and prostate cancer patients Hiedelberg Ion-Beam Radiotherapy Center (HIT) started treating patents with carbon in clinical facility in 2009 New facilities in Europe under way, some will start very soon Manjit Dosanjh 15

16 The Darmstadt GSI pilot project ( ) 450 G. Kraft J. Debus Manjit Dosanjh 16

17 The PIMMS Collaboration Collaboration was formed in 1996 following an agreement between Med AUSTRON (A) and TERA (I) CERN agreed to host and support the study in PS The study was later joined by ONKOLOGY 2000 (CZ) Close contacts were kept with GSI (D) Work started in January 1996 and continued for 4 years. Final report is available (CD ROM;CERN Yellow Report) Manjit Dosanjh 17

18 Schematic Layout of the PIMMS Design Main Accelerator dump Injection Chain proton linac proton source Synchrotron protons and C-ions dump C-ion linac C-ion source Treatment rooms beam diagnostic Slow Extraction room 1 proton gantry room 2 proton horizontal room 3 proton gantry room 4 C-ion horizontal room 5 C-ion gantry p+c-ions Manjit Dosanjh 19

19 Conclusions PIMMS is best suited to light ion therapy Designed for high precision active scanning with a gantry Extraction optimised for a smooth spill and (short treatments ~2 min) Extraction lines exploit special properties of slow extracted beam Modular design of extraction lines integrated with the gantries Manjit Dosanjh 20

20 The European Ion Beam Facilities Kiel WPE Essen Berlin Asclepios Caen Aachen GSI Darmstadt Marburg HIT Heidelberg Orsay I & II Paris RPTC Munich PSI Villingen MedAustron Wiener Neustadt Manjit Dosanjh 21

21 Carbon ion facilities In Asia: Light Ion Therapy Facilities 3 in operation: Chiba, Harima, Gunma (Japan) 3 under construction: Shanghai (China), 2+ Japan In Europe: HIT in operation, Heidelberg (Germany), CNAO Pavia (Italy) almost ready to treat patients Marburg (Germany) nearly finished Kiel (Germany) in constuction Wiener Neustadt (Austria) construction starts tomorrow! ETOILE in Lyon, France ARCHADE in Caen (France) GSI/Siemens: Heidelberg Manjit Dosanjh 22

22 Tumor Sites in Carbon Ion RT (6.1994~2.2007) Esophagus 47(1.5%) Eye 70(2.2%) HAMT: 28 Pancreas 84(2.7%) Rectum 88(2.8%) HAMT: 50 CNS 93(2.9%) Skull Base 46(1.5%) HAMT: 17 Uterus 115(3.6%) Lacrymal Gl 12(0.4%) Total 3,178 HAMT:1,077 Liver 212(6.7%) HAMT: 15 Miscellaneous 662(20.9%) HAMT:403 Bone & Soft Tissue 349(11.0%) HAMT: 175 Prostate 515(16.3%) HAMT: 242 Lung 467(14.7%) HAMT: 17 Head & Neck 408(12.9%) HAMT: 125 Manjit Dosanjh 23

23 The Number of Fractions in Carbon Ion RT No. Fractions 照射回数 回の治療当り平均 :14 回 The entire course of treatment Has been given by carbon ions alone 年度 Yr. Average No. of fractions per patient is 12 Manjit Dosanjh 24

24 Dose planning at GSI/HIT vs HIMAC carbon ion At GSI and HIT the dose planning for patients is based on the local effect model (LEM) At HIMAC, HIBMC and GMHC the dose planning is based on the neutron normal physical dose response Future.. Dose planning for patients will also be considered using the microdosimetric-kinetic (MK) model in combination with different Monte Carlo (MC) codes e.g. GEANT2, PHITS, SHIELD-HIT and FLUKA, to provide clinical calculated absorbed and RBE weighted doses Manjit Dosanjh 25

25 ENLIGHT European Network for Light Ion Hadron Therapy Manjit Dosanjh 26

26 ENLIGHT Why did we need a network? Why the timing 2001? What was necessary for a network? Which activities were needed to catalyse ENLIGHT? Which were the key starting points? Manjit Dosanjh 27

27 ENLIGHT was established to Create common multidisciplinary platform Share knowledge Share best practices Harmonise data Provide training, education Identify challenges Innovate Lobbying for funding Manjit Dosanjh 28 28

28 Challenges for a network Multidisciplinary and cutting edge technologies: Clinical Studies Radiobiology Treatment planning for Particle Therapy Adaptive ion therapy and treating of moving organs Novel imaging PET systems Feasibility study for innovative gantry designs Improved gantry design Manjit Dosanjh 29 29

29 ENLIGHT++ challenges A heterogeneous group many different disciplines How to balance between basic research and the clinical needs? Many partners. How to give space to each and make progress with the main objectives? How to strike a balance between agenda of the single centres and the ENLIGHT++ goals? Can we show ion therapy is more effective? Manjit Dosanjh 30

30 The birth of ENLIGHT ENLIGHT was launched at CERN in Feb 2002 In 2002, ENLIGHT was composed of ESTRO, the European Society for Therapeutic Radiology and Oncology ETOILE, Lyon, France Karolinska Institute, Sweden GSI/GHIP (German Heavy Ion Project), Germany Med Austron, Austria TERA, Italy CERN, Switzerland ENLIGHT was funded as a network by the European Commission between Manjit Dosanjh 31

31 Bridging the gap A major achievement of ENLIGHT is bringing together of various communities so that clinicians, physicists, biologists and engineers interested in particle therapy are working together for research, funding and lobbying Manjit Dosanjh 32

32 From ENLIGHT... ENLIGHT++ In 2006 ENLIGHT became + More than a network.research + More inclusive..more institutions, more countries The network itself continued even without funding Develop strategies for securing the funding for specific projects under the umbrella of ENLIGHT, along two major axes - Research in areas needed for improving hadron therapy - Networking, to establish and implement common standards, protocols for treating patients, training and education Now we have >300 participants from 20 European countries Manjit Dosanjh 33

33 ENLIGHT is helping to get funding In 2011, under the umbrella of ENLIGHT, there are now 4 EC funded projects: Three ongoing projects: PARTNER, ULICE and ENVISION with a total funding of 24 M Euros midterm PARTNER at Karolinska in Sept 2010 The newest training project, ENTERVISION, started in February 2011 in Lyon Manjit Dosanjh 34

34 4 year Marie Curie Training project Funded by the EC with 5.6 M Euros Started in September 2008 Aims at the creation of the next generation of experts PARTNER Particle Training Network for European Radiotherapy Brings together key academic institutes and research centres and the two leading European companies in particle therapy (IBA and Siemens) Research and training opportunities for 25 young biologists, engineers, physicians and physicists PARTNER is funded by the European Commission under Grant Agreement Number Manjit Dosanjh 35

35 Multidisciplinary PARTNERships to fight cancer Clinical Studies Epidemiology & Patient Selection Radiobiology Treatment Planning Simulation and Dosimetry Image Guided Hadron Therapy PET prototype, In situ Monitoring Novel Gantry ICT and prototype GRID Novel accelerator study Courtesy CNAO Courtesy GSI/HIT/Siemens CERN CNAO ETOILE GSI IBA IFIC KI MEDAUSTRON SIEMENS TERA UKL HD UNIS Manjit Dosanjh 36

36 ULICE: Union of Light Ion Centres in Europe Addresses two complementary issues: Development of appropriate instruments for high performance hadron therapy Courtesy GSI/HIT/Siemens Need for close collaboration among the existing and planned centres The ULICE project started in September 2009 Funded for 4 years by the EC with 8.4 M Euros 20 European institutions ARC AUH,AS CERN CNAO ESTRO ETOILE GSI IBA IFJPAN INFN KI MEDA MUW RUNMC SAG TUD UCL UKL HD UNIMAR UOXF Manjit Dosanjh 37

37 The 3 pillars of ULICE Joint Research Activities - aims at improving the performance of hadron therapy facilities by research and development Networking Activities Communication among the 20 partners and with the external world Transnational Access provides access for external researchers to the recently opened ion therapy facilities The ULICE project is co funded by the European Commission under FP7 Grant Agreement Number Manjit Dosanjh 38

38 ENVISION: European Novel Imaging Systems for Ion Therapy Accurate positioning is a crucial challenge for targeting moving organs during treatment ENVISION aims at developing solutions for: real time monitoring quantitative imaging precise determination of delivered dose fast feedback for optimal treatment planning real time response to moving organs Simulation studies adapted from Parodi et al, IJROBP 68 (2007) The ENVISION project is co-funded by the European Commission under FP7 Grant Agreement N Manjit Dosanjh 39

39 ENVISION A 4 year EU funded project started in February 2010, ENVISION is a collaboration of 16 leading European research centres and industrial partners for 6M Euros. Five work packages Time of Flight in beam PET In beam single particle tomography In vivo dosimetry and moving target volumes The combination of in vivo dosimetry, treatment planning, and clinical relevance Monte Carlo simulation of in vivo dosimetry CERN CNRS CISC GSI IBA INFN MAASTRO MUW OXFORD POLIMI TERA TUD UCBL UCLM UGENT UKL HD Manjit Dosanjh 40

40 ENTERVISION Research Training in Imaging for Cancer Radiation Therapy ENTERVISION fills the need for reinforcing research and training of young researchers in all aspects of imaging Interdisciplinary and multinational initiative Many training courses open to external young researchers ENTERVISION brings together ten academic institutes and and the two leading European companies in particle therapy, IBA and Siemens. The network will train 16 Researchers during a 4 year period. The ENTERVISION project is co-funded by the European Commission under FP7 Grant Agreement N Manjit Dosanjh 41

41 In conclusion.. ENLIGHT provides a powerful multidisciplinary European collaboration amongst interested partners ENLIGHT acts as a platform for defining research needs Developing projects and getting them funded Lobbying politically (e.g. France, Poland, UK) ENLIGHT is a useful resource for communities interested in hadron therapy and establishing facilities Clear desire for continuing to collaborate on new and existing research topics and helping new initiatives. Manjit Dosanjh 42

42 Number of patients treated 1st proposed by Wilson in st proton therapy conducted by Lawrence in st treatment in Uppsala in 1957 By 2010, patients patients worldwide have been treated protons, 7151 C ions In Europe 9 facilities: patients ( ) (Dr. Martin Jermann, PTCOG meeting, 2010) Manjit Dosanjh 43

43 Hadrontherapy goals Provide the irradiation technologies and the detection systems to optimally use the advantages of charged particles organs at risk Optimize the dose to the tumour by beam scanning and adaptation of the delivery e.g. organ motion, respiration tumour Treat around patients and perform clinical trials using low LET and high LET beams Conduct technical, physical, radiobiological and clinical R+D tumour-conformal dose distribution Manjit Dosanjh 44