1. http://www.adams-institute.ac.ukKen.Peach@adams-institute.ac.ukhttp://www.basroc.org.uk British Accelerator Science & Radiation Oncology Consortium A new accelerator for advanced research and cancer therapy Ken Peach John Adams Institute for Accelerator Science University of Oxford and Royal Holloway University of London RHUL 22 nd October 2008

2. Ken PeachJohn Adams Institute 22 X 082 Outline Introduction (Accelerators & Particle Physics) The Neutrino Factory (Why? The Muon Acceleration Challenge) The ns-FFAG Accelerator (non-scaling Fixed-Field Alternating Gradient) EMMA Charged Particle Therapy (CPT) (proton and light-ion cancer treatment) PAMELA Summary

3. Ken PeachJohn Adams Institute 22 X 083 Introduction There are more than 17,000 particle accelerators (> a few MeV) worldwide –Most are used in medicine Linacs, cyclotrons, some synchrotrons… –Next most common in industry Ion implantation etc –Synchrotron Radiation Sources Mostly synchrotrons, coming soon - linacs –Neutron and radionuclide sources Linacs, cyclotrons, synchrotrons, something weird and –For particle physics! A few big synchrotrons (& colliders) –Often with Linacs at the front end And coming soon (maybe) the ILC

4. Ken PeachJohn Adams Institute 22 X 084 Classical Accelerator Types TypeMagnetic Field RFRadius BetatronVariable × Fixed CyclotronFixed Variable SynchrotronVariable Fixed FFAGFixed ~Fixed Linear accelerators (Linacs) ×  + assorted others – electrostatic, RFQs etc … + new ideas (laser-plasma for example) …

5. Ken PeachJohn Adams Institute 22 X 085 The Bleeding Edge? Medical accelerators –Mainly linacs and cyclotrons Research accelerators –Mainly synchrotrons Particle Physics applications –Better synchrotrons (LHC) –Better linacs (ILC) Why do we need anything new? –Because life presents new challenges!

6. Ken PeachJohn Adams Institute 22 X 086 HiggsBosonHiggsBoson? Force Carriers Z Z boson W W boson  photon g gluon Generations of matter Generations of matter   -neutrino  tau b bottom t top III   -neutrino  muon s strange c charm II e e-neutrino e electron d down up uI Leptons Quarks Particles and Forces Each with its own ‘antiparticle’ © Brian Foster

7. Ken PeachJohn Adams Institute 22 X 087 The Standard Model The Parameters 6 quark masses –m u, m c, m t –m d, m s, m b 3 lepton masses –m e, m , m  2 vector boson masses –M w, M Z (m , m g =0) 1 Higgs mass –M h 3 coupling constants –G F, ,  s 3 quark mixing angles –  12,  23,  13 1 quark phase – 

8. http://www.adams-institute.ac.ukKen.Peach@adams-institute.ac.ukhttp://www.basroc.org.uk British Accelerator Science & Radiation Oncology Consortium Neutrino Factory The “ultimate” neutrino facility

9. Ken PeachJohn Adams Institute 22 X 089 The Standard Model The Parameters 6 quark masses –m u, m c, m t –m d, m s, m b 3 lepton masses –m e, m , m  2 vector boson masses –M w, M Z (m , m g =0) 1 Higgs mass –M h 3 coupling constants –G F, ,  s 3 quark mixing angles –  12,  23,  13 1 quark phase –  Neutrino sector Neutrino masses identically 0!!!!

10. Ken PeachJohn Adams Institute 22 X 0810 Neutrino Mixing Parameters of neutrino oscillation 1 absolute mass scale 2 squared mass diffs 3 mixing angles 1 phase 2 Majorana phases solarAtmospheric Majorana 3G c ij =cos q ij s ij =sin q ij 22 Fogli et al, 2008

11. Ken PeachJohn Adams Institute 22 X 0811 a =2  2 G F n e E = 7.6 10 -5  E Where is the electron density ;  is the density (g/cm 3 ) ; E is the neutrino energy (GeV ) Why is it hard to measure the parameters? (Richter: hep-ph/0008222) c ij =cos  ij, s ij =sin  ij

12. Ken PeachJohn Adams Institute 22 X 0812 What to Measure? Neutrinos e disappearance e   appearance e   appearance  disappearance   e appearance    appearance … and the corresponding antineutrino interactions Note: the beam requirements for these experiments are: high intensityknown flux known spectrum known composition (preferably no background)

13. Ken PeachJohn Adams Institute 22 X 0813 CP-violation FNAL Feasibality Study 1

14. Ken PeachJohn Adams Institute 22 X 0814 A Neutrino Factory is … … an accelerator complex designed to produce >10 20 muon decays per year directed at a detector thousands of km away Muon Acceleration … need to accelerate muons very quickly [@5 GeV,   ~0.1msec]

15. Ken PeachJohn Adams Institute 22 X 0815 Neutrino Factory cost drivers High Power proton drivers –MW power, ns pulses RLA or FFAG? –Which is cheaper? RF –30% of the cost? Cooling –How much? (20% of the cost?) BNL Feasibality Study 2

16. http://www.adams-institute.ac.ukKen.Peach@adams-institute.ac.ukhttp://www.basroc.org.uk British Accelerator Science & Radiation Oncology Consortium The non-scaling FFAG Accelerator Fixed-Field Alternating Gradient

17. Ken PeachJohn Adams Institute 22 X 0817 Fixed Field Alternating Gradient accelerators Fixed-Field (like a cyclotron) –Rapid acceleration possible –Rapid cycling possible Alternating Gradient (like a synchrotron) –Focussing!!!! Small (er) magnets/beam pipe/vacuum system … and large acceptance The best of both worlds! –So why is the world not full of FFAGs? TypeMagnetic FieldRFRadius FFAGFixed ~Fixed

18. Ken PeachJohn Adams Institute 22 X 0818 Early FFAGs (1955-1960) MURA built several electron FFAGs in the 1950s 20 to 400 keV machine ChandrasekharBohr Radial sector Spiral sector Large complicated magnets c.f. Cyclotron – large simple magnets c.f. Synchrotron – small simple magnets

19. Ken PeachJohn Adams Institute 22 X 0819 Newer FFAG’s (post-2000) The Japanese have built two “proof of principle” proton FFAGs 500 keV proton FFAG @ KEK150 MeV proton FFAG @ KEK

20. Ken PeachJohn Adams Institute 22 X 0820 … but … Why? LARGE COMPLICATED … the magnets are LARGE and COMPLICATED Why does k have to be so large? 1.Larger k means stronger focussing 2. k > 0 means horizontal focussing –This means that the average field increases with radius 3.The momentum compaction   1/(k+1) –Large momentum bite  small orbit excursion Orbit excursion ~ 0.9m + where k >> 1

21. Ken PeachJohn Adams Institute 22 X 0821 Scaling and non-scaling FFAGs where k >> 1 where k = 1 Linear Linear magnets! i.e. quadrupoles Invented in 1999

22. Ken PeachJohn Adams Institute 22 X 0822 Simpler Magnets LARGE COMPLICATED … the magnets are LARGE and COMPLICATED B0B0 xx SMALL SIMPLE to magnets that are SMALL and SIMPLE

23. Ken PeachJohn Adams Institute 22 X 0823 The ns-FFAG Should combine the advantages of FFAGs –Fixed Field Fast cycling (limited essentially by RF) Simpler, cheaper power supplies No eddy-currents High intensity (pulsed, ~continuous) Low beam losses Easier maintenance and operation Lower stresses –Strong Focussing Magnetic ring Variable energy extraction Higher energies (than cyclotrons) Different ion species possible with relative ease of construction

24. Ken PeachJohn Adams Institute 22 X 0824 … so … where is the catch? Variable tune! Tune ~    c Must cross resonances

25. Ken PeachJohn Adams Institute 22 X 0825 Beam Acceleration coherentResonance is a coherent effect –Can fast acceleration circumvent the resonances? If the momentum changes by a large amount during a single turns, is it possible to leap-frog over the resonance? –Small variation of the path length with momentum (small momentum compaction) Fixed radio-frequency cavities? 10MeV 20MeV |df/f|~0.1% 0.1ns Plots for EMMA

26. Ken PeachJohn Adams Institute 22 X 0826 Does it work? We do not know! –There is no “no-go” theorem Need for a “proof of principle” demonstrator –EMMA Electron Model for Many Applications –Originally Electron Model for Muon Acceleration Funding obtained in the UK to design and build a EMMA – the world’s first non-scaling FFAG accelerator!

27. Ken PeachJohn Adams Institute 22 X 0827 Objectives of the CONFORM Project 1.Show the non-Scaling Fixed-Field Alternating Gradient Accelerators work Build an Electron Model (EMMA) Design a prototype Charged Particle Therapy machine based on ns-FFAGs Protons and carbon ions 2.Develop applications of ns-FFAGs

28. Ken PeachJohn Adams Institute 22 X 0828 EMMA Parameters 42 identical straight length 394.481 mm Long drift210.000 mm F Quad58.782 mm Short drift50.000 mm D Quad75.699 mm

29. Ken PeachJohn Adams Institute 22 X 0829 Location of EMMA Daresbury

30. Ken PeachJohn Adams Institute 22 X 0830 EMMA at the ERLP@Daresbury After Neil Bliss ERLP Parameters

31. Ken PeachJohn Adams Institute 22 X 0831 EMMA: Lattice & Magnets B0B0 xx Magnet linear slide After Neil Bliss

32. Ken PeachJohn Adams Institute 22 X 0832 Diagnostics, injection & extraction After Rob Edgecock

33. Ken PeachJohn Adams Institute 22 X 0833 Status of EMMA Funded! (~£6M) –Started 1 st April 2007 Lattice- fixed Component design- ongoing –Prototype quads being measured now Final design- complete Jan 08 Construction- complete Jul 09 Beam studies- until Sep 10 –At least … After Tkeichiro Yokoi

34. Ken PeachJohn Adams Institute 22 X 0834 CONFORM

35. http://www.adams-institute.ac.ukKen.Peach@adams-institute.ac.ukhttp://www.basroc.org.uk British Accelerator Science & Radiation Oncology Consortium PAMELA Charged Particle Therapy (CPT) BASROC & CONFORM

36. Ken PeachJohn Adams Institute 22 X 0836 Incidence of Cancer in the UK 12.5% probability, all types (except skin cancer) by 65 –Rises to more than 1/3 rd for whole-life –Around half are associated with specific risks –Statistically, some will be close to sensitive tissue and difficult to treat surgically or chemically Source: Cancer Research UK

37. Ken PeachJohn Adams Institute 22 X 0837 An important statistic “ Radiotherapy remains a mainstay in the treatment of cancer. Comparison of the contribution towards cure by the major cancer treatment modalities shows that of those cured, 49% are cured by surgery, 40% by radiotherapy and 11% by chemotherapy”. RCR document BFCO(03)3, (2003). Chemotherapy provides by far the smallest contribution towards cancer cure yet is much more expensive than radiotherapy and generates a disproportionately large research and media interest. Roger Dale, Hammersmith Hospital and Imperial College

38. Ken PeachJohn Adams Institute 22 X 0838 What is RBE? RBE = Relative Biological Effectiveness. A measure of the biological “potency” of a particular type of radiation relative to that of a reference radiation. Reference radiation (conventional x-rays) has RBE = 1 For a given biological end-point: Proton RBEs: ~ 1.1 Neutron RBEs: 3 - 5 Carbon ion RBEs: 3 - 5 Roger Dale, Hammersmith Hospital and Imperial College

39. Ken PeachJohn Adams Institute 22 X 0839 The concept and definition of RBE are both straightforward. Unfortunately…. Even for a particular type of radiation, RBE is not fixed. Its value depends on: a) The size of the dose used at each treatment b) The chosen biological end-point c) The nature of the irradiated tissue Roger Dale, Hammersmith Hospital and Imperial College

40. Ken PeachJohn Adams Institute 22 X 0840 Development of Cancer Radiotherapy 1895 : Konrad Rontgen’s X- rays1895 : Konrad Rontgen’s X- rays 1898 - Marie Curie’s Radium1898 - Marie Curie’s Radium Radium and x-ray machines used to treat cancerRadium and x-ray machines used to treat cancer Most current radiotherapy uses High energy X-ray beams from linear accelerators or ‘linacs’Most current radiotherapy uses High energy X-ray beams from linear accelerators or ‘linacs’ These X-ray beams pass through entire thickness of bodyThese X-ray beams pass through entire thickness of body Modern Linac

41. Ken PeachJohn Adams Institute 22 X 0841 X-ray therapy began within months of Roentgen’s discovery

42. Ken PeachJohn Adams Institute 22 X 0842 Present status of cancer in society Cancer arises in 40% of populationCancer arises in 40% of population Most forms increase with age and  prevalence expected to increaseMost forms increase with age and  prevalence expected to increase Therapy has side effects (mild to severe, and sometimes permanent)……there can be no complacencyTherapy has side effects (mild to severe, and sometimes permanent)……there can be no complacency Molecular approaches have produced limited gains so farMolecular approaches have produced limited gains so far Earlier diagnosis is increasingly possibleEarlier diagnosis is increasingly possible

43. Ken PeachJohn Adams Institute 22 X 0843 Curing Cancer with X-rays Dose Linac

44. Ken PeachJohn Adams Institute 22 X 0844 Radiotherapy linacs

45. Ken PeachJohn Adams Institute 22 X 0845 Intensity Modulated Radiation Therapy (IMRT)

46. Ken PeachJohn Adams Institute 22 X 0846 Bragg peak Plateau Carbon Ion Beam Profile The Bragg Peak

47. Ken PeachJohn Adams Institute 22 X 0847 Can we do better? Dose Proton The Bragg Peak

48. Ken PeachJohn Adams Institute 22 X 0848 Is it better?

49. Ken PeachJohn Adams Institute 22 X 0849 100 60 10 X-rays With Protons Medulloblastoma in a child

50. Ken PeachJohn Adams Institute 22 X 0850 (from Gillies McKenna) “When proton therapy facilities become available it will become malpractice not to use them for children.” Herman Suit, M.D., D.Phil. Chair, Radiation Medicine Massachusetts General Hospital

51. Ken PeachJohn Adams Institute 22 X 0851 A Proton Therapy Centre

52. Ken PeachJohn Adams Institute 22 X 0852 A rotating gantry

53. Ken PeachJohn Adams Institute 22 X 0853 The Clatterbridge Centre for Oncology Established 1989 –First hospital based proton therapy –>1400 patients with ocular melanoma –First example of 3D computer treatment planning in UK; eye gaze direction used to obtain best approach angle to eye. Unsung success story of British Oncology! After Bleddyn Jones

54. Ken PeachJohn Adams Institute 22 X 0854 Can we do even better? Dose Carbon

55. Ken PeachJohn Adams Institute 22 X 0855 X-rays protons The Spread-Out Bragg Peak

56. Ken PeachJohn Adams Institute 22 X 0856 Why use protons? After Bleddyn Jones X-Rays 100 80 150 60 Protons 30050 60 0

57. Ken PeachJohn Adams Institute 22 X 0857 Cancer of the Kidney Stage I: TIa N0 M0 80GyE / 16fr. /4wks 治療前 1 year 2 years 3 years 5 years Does it work? From Japan

58. Ken PeachJohn Adams Institute 22 X 0858 Prostate Cancer Results Loma Linde

59. Clinical uses Inoperable brain tumours Head and neck tumours Prostate tumours Paraspinal tumours Thoracic tumours (some) In addition – Radiobiology programme – Cell line and animal irradiations From Alex Elliott

60. Intracranial Tumour 17 month old child From Alex Elliott

61. Rectal carcinoma Protons reduce radiation toxicity and dysfunction From Alex Elliott

62. Ken PeachJohn Adams Institute 22 X 0862 Japan: Tsukuba University New Proton Medical Research Centre, 2001

63. Ken PeachJohn Adams Institute 22 X 0863 C-ion Dose Distribution in Lung cancer: Chiba, Japan

64. Ken PeachJohn Adams Institute 22 X 0864 Liver cancer Primary liver cancer treated by carbon ionsPrimary liver cancer treated by carbon ions 5 year follow up in cured patient5 year follow up in cured patient

65. Ken PeachJohn Adams Institute 22 X 0865 Expected and achievable benefits Reduce fear of cancer treatment, improved patient experience,Reduce fear of cancer treatment, improved patient experience, Dose increase to cancer : 1% increase in cancer control per unit increase in dose …..i.e. 15 Gy extra  15% extra control.Dose increase to cancer : 1% increase in cancer control per unit increase in dose …..i.e. 15 Gy extra  15% extra control. Dose reduction to organs e.g. lung, brain, eye, spine, bowel, bone: leading to reduced or absence of many side effectsDose reduction to organs e.g. lung, brain, eye, spine, bowel, bone: leading to reduced or absence of many side effects Chemotherapy better toleratedChemotherapy better tolerated Better quality of life, ability to contribute to society etc.Better quality of life, ability to contribute to society etc.

66. Ken PeachJohn Adams Institute 22 X 0866 World & UK Position USA 12 centres, Germany 6, Japan 8.USA 12 centres, Germany 6, Japan 8. Italy, Switzerland, Sweden, France all have facilities with plans for expansion and large new centresItaly, Switzerland, Sweden, France all have facilities with plans for expansion and large new centres Cancer Reform Strategy (2007): arrangements for patients to be sent abroad: 12 in first year, Perhaps up to 400. Explore business case for UK Centre(s)Cancer Reform Strategy (2007): arrangements for patients to be sent abroad: 12 in first year, Perhaps up to 400. Explore business case for UK Centre(s)

67. Ken PeachJohn Adams Institute 22 X 0867 Spot Scanning Target Magnetic scanner ‘Range shifter’ plate Patient Proton pencil beam Pedroni et al, Med Phys. 22:37-53, 1995

68. Ken PeachJohn Adams Institute 22 X 0868 Why use Carbon? Daniela Schulz-Ertner, Heiddelberg

69. Ken PeachJohn Adams Institute 22 X 0869 CPT facilities operating & planned

70. Ken PeachJohn Adams Institute 22 X 0870 Hadron Therapy in Chiba (Japan) Borrowed from Rob Edgecock

71. Ken PeachJohn Adams Institute 22 X 0871 The requirements There are obvious potential benefits from proton/light ion therapy –Need to maximise the benefits Requirements –Rapid variable energy extraction –Rapid variable transverse spot scanning –Variable ion species –Accurate dose measurements Flux control

72. Ken PeachJohn Adams Institute 22 X 0872 PAMELA Objectives Produce the conceptual design for a combined proton/carbon/light ion cancer therapy facility –250 MeV protons, 400 MeV/u Carbon Preliminary performance parameters –>100 Hz cycle rate and one turn ejection –Dose rate of 2 to 10 Gy/minute. (1Gy ~ 2 x 10 10 protons) –Voxel size from 4x4x4 mm 3 to 10x10x10 mm 3 –Up to 100 pulses/voxel With a typical tumour volume of 250 cm 3 & voxel- volume 0.064 cm3 (4x4x4), there are 4,000 elements, which with 10 to 100 pulses for each voxel needs 40k to 400k pulses in around 300 seconds, or a cycle rate of 133 Hz to 1.3 kHz.

73. Ken PeachJohn Adams Institute 22 X 0873 Accelerator Technology? 4 possible technologies –Cyclotrons Fixed energy extraction, difficult for Carbon at full energy (equivalent to 1.2 GeV/c protons) –Synchrotrons Flexible, but difficult to meet the pulse requirements; slow extraction difficult; normal conducting machine (stability?) –(ns) FFAG Flexible, rapid cycling (fixed field), variable energy … but … unproven technology –Laser-Plasma Ion accelerators Far in the future …

74. Ken PeachJohn Adams Institute 22 X 0874 Synchrotron Cyclotron FFAG Intensity (>100nA) LowPlenty Plenty 1-16nA >100nA Maintenance HardNormalNormal Extraction eff Good Poor Good? OperationNot easy Easy Easy Ions Yes No Yes Variable energy Yes No Yes Multi-extractionPossible No Yes After Y.Mori KEK/Kyoto Advantages of FFAG in Charged Particle Therapy

75. Ken PeachJohn Adams Institute 22 X 0875 Challenges The non-relativistic, non-scaling Fixed-Field Alternating Gradient Accelerator (nrns-FFAG) is a new type of accelerator –Very dense lattice –Challenging magnets, RF, injections and extraction –Resonance crossing –Stability EMMA will demonstrate the ns-FFAG PAMELA will demonstrate the nrns-FFAG

76. Ken PeachJohn Adams Institute 22 X 0876 Status Studies underway using a test lattice –Magnets – probably combined function superconducting magnets –RF – a number of schemes are being considered –Injection and extraction – will constrain the lattice parameters Aim –Design a new lattice with a cell that can be engineered by end of 2008 –Work through the design in 2009 –Incorporate the lessons from EMMA –Produce a conceptual design in 2010

77. Ken PeachJohn Adams Institute 22 X 0877 PAMELA Particle Accelerator for MEdical Applications Fixed Field Alternating Gradient Accelerator Protons or carbon ions

78. Ken PeachJohn Adams Institute 22 X 0878 PAMELA

79. Ken PeachJohn Adams Institute 22 X 0879 Superconducting FFAG Gantries Fixed field of 3.7T Transports 150-400 MeV/u Length ~15m D Trbojevic/BNL

80. Ken PeachJohn Adams Institute 22 X 0880 BASROC

81. Ken PeachJohn Adams Institute 22 X 0881 Summary Non-scaling FFAG accelerators are: –New –Untried –Interesting for Neutrino physics Cancer therapy –And other applications »Spallation neutron sources, muon sources »Accelerator driven reactors, nuclear waste disposal We will know in ~3 years if they work –Let us hope that they do … they could be very useful devices …