III. Proton-therapytherapy. Rome SB - 5/5 1

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1 Outline Introduction: an historical review I Applications in medical diagnostics Particle accelerators for medicine Applications in conventional radiation therapy II III IV Hadrontherapy, the frontier of cancer radiation therapy Proton-therapytherapy Carbon ion therapy Neutrons in cancer therapy V Rome SB - 5/5 1

2 Hadrontherapy with beams of protons and ions Rome SB - 5/5 2

3 Charged particles in matter The Bethe-Bloch Bloch formula: = = MeV / (g/cm 2 ) dx expressed in g/cm 2 Notes: Ionization + eccitation MIP = Minimum Ionizing Particle MIP in water 2.0 MeV/cm 0.2 ev/nm very low LET radiation! Rome SB - 5/5 3

4 The basic concept of hadrontherapy Fundamental physics Particle identification L3 at LEP Medical applications Cancer hadrontherapy Rome SB - 5/5 4

5 The Bragg peak Straggling and multiple scattering Fragmentation Rome SB - 5/5 5

6 Single beam comparison X rays Protons or Carbon ions Rome SB - 5/5 6

7 Protons and ions are more precise than X X--rays Tumour between the eyes 9 X ray beams Rome SB - 5/5 1 proton beam 7

8 The first idea Bob Wilson, 1946 Bob Wilson was student of Lawrence in Berkley Study of the shielding for the new cyclotron Interdisciplinary i environment = new ideas! Use of protons and charged hadrons to better distribute the dose of radiation in cancer therapy R.R. Wilson, Radiology, 47 (1946) 487 Rome SB - 5/5 8

9 The beginning of hadrontherpay 1954 at Berkeley C.A. Tobias, J.H. Lawrence et al., Cancer Research 18 (1958) 121 Rome SB - 5/5 9

10 The basic principles of hadrontherapy Protons 200 MeV 1nA 27 cm Tumour targett Carbon ions 4800 MeV 0.1 na Beam of hadrons which slow down in matter Bragg peak Better conformity of the dose to the target t healthy tissue sparing Hadrons are charged Beam scanning for dose distribution Heavy ions Higher biological effectiveness Rome SB - 5/5 10

11 Energy and current Why 200 MeV protons and 400 MeV/u C ions? Range in water: 200 MeV p 27 cm penetration depth 4800 MeV C ions 27 cm penetration depth Why 1 na current? Requirement: 2 Gy per Kg per minute (2 J / 200 MeV) x (e) x (1/60 sec) 1 na Rome SB - 5/5 11

12 Why ions have a large biological effectiveness? X RBE = 1 RBE = 3 quantum Break of a single/double helix of DNA carbon ion 40 mm from the end of the range electron ionization Multiple breaks of both helixes cannot tbe repaired cromosome Ions have high LET (Linear Energy Transfer) Rome SB - 5/5 12

13 The eye melanoma treatment at INFN-LNS in Catania LNS Supercoducting cyclotron 65 MeV protons 92 patients (oct 2005) Rome SB - 5/5 13

14 First hospital-based proton-therapy therapy centre, built in 1993 ~160/sessions a day ~1000 patients/year The Loma Linda University Medical Center (USA) Rome SB - 5/5 14

15 Dose distribution: passive spreading Double scattering Layer stacking Rome SB - 5/5 15

16 Standard procedure: Passive beam spreading with respiratory gating Double scatterer Collimator Bolus: has to be machined for each case. Rome SB - 5/5 16

17 Advanced procedure: layer stacking with respiratory gating Collimator adapted to transverse shape of each slice. Rome SB - 5/5 17

18 Passive spreading: the nozzle Ionization chamber Propeller Quadrant ionization chamber Beam Rome SB - 5/5 18

19 Passive spreading: calibration before treatment Collimator Bolus Water equivalent absorber Ionization chamber Rome SB - 5/5 19

20 Passive spreading: personalized devices Propeller Collimator Bolus - prostate Bolus - liver Rome SB - 5/5 20

21 Dose distribution: active scanning Longitudinal plane Transverse plane patient fast slow beam horizontal scanning vertical scanning beam tumour volume energy variation New technique developed mainly at GSI and PSI Rome SB - 5/5 21

22 Active spot scanning a la PSI 1 2 Single spot Lateral scanning with magnet: 2 ms/step 3 4 Depth scanning with upstream absorbers Depth scanning Third scanning by a bending magnet and movable bed Rome SB - 5/5 22

23 High precision RT with proton beams Rome SB - 5/5 23

24 High precision RT with proton beams Rome SB - 5/5 24

25 High precision RT with proton beams Rome SB - 5/5 25

26 High precision RT with proton beams Rome SB - 5/5 26

27 Front-end boards A detector for spot scanning: The strip chamber developed by TERA for PSI Mylar window Mylar window U Anode In collaboration with University and INFN Torino 2-sided aluminized cathode T Anode Rome SB - 5/5 27

28 Beam tests on Gantry1 at PSI SAMBA Strip Accurate Monitor for Beam Applications Measurement of a spot Rome SB - 5/5 28

29 Time profile of the clinical beams Tota al Intensit ty SPOTS Average flat top current 0.2 na Time 5 ms Rome SB - 5/5 29

30 A line of dose made of spots Rome SB - 5/5 30

31 Number of potential patients Study by AIRO, 2003 Italian Association for Oncological Radiotharapy X-ray therapy every 10 million inhabitants: 20' pts/year Protontherapy 14.5% of X-ray patients = 2'900 pts/year Therapy with Carbon ions for radio-resistant resistant tumours 3% of X-ray patients = 600 pts/year Every 50 M inhabitants Proton-therapytherapy 4-5 centres Carbon ion therapy 1 centre TOTAL about 3'500 pts/year every 10 M Rome SB - 5/5 31

32 The sites Up to present Proton-therapy: therapy: ~ patients Carbon ion therapy: ~ patients t Rome SB - 5/5 32

33 Tumours of the central nervous system Control at 5 years RT Protons Chordomas 17-50% 73-83% Chondrosarcomas 50-60% 90-98% 98% Rome SB - 5/5 33

34 The map of hadrontherapy Rome SB - 5/5 34

35 What a patient sees Rome SB - 5/5 35

36 A ganrty for proton therapy Rome SB - 5/5 36

37 A research topic: proton radiography CT gives information on the density of electrons (Hounsfield numbers) CT is commonly used in diagnostics CT is commonly used in conventional radiation therapy to calculate the treatment planning X and MeV gamma rays interact with the electrons CT is used also in proton and ion therapy to calculate the treatment planning but Protons and ions interact with matter through de/dxdx -> density ρ, Z Compton effect is proportional to Z but not the photoelectric effect! Corrections are applied Rome SB - 5/5 37

38 Proton radiography and proton CT Radiography with X-rays Counts the number of photons (attenuation coefficient) Proton radiography Protons with enough energy to penetrate the body Residual range mesurement Rome SB - 5/5 38

39 Proton radiography Scintillating fibers Advantages No need for corrections like for X-ray CT Less dose to the patient (every proton brings information!) Disadvantages E. Pedroni et al., PSI Need of large accelerators usually used also for therapy (timing problem) For now it is a research issue (PSI) Rome SB - 5/5 39

40 Carbon ion therapy in Europe GSI pilot project (G. Kraft) 200 patients t treated t with carbon ions PET on-beam Rome SB - 5/5 40

41 PET on-beam Simulated from TPS Measurement of the real dose given to the patient Measured Rome SB - 5/5 41

42 HIT University of Heidelberg Carbon ion gantry MAN technology December 2006 Hospital based centre Architects Nickl & Partner, Munich and Heidelberg University Building Authority Project started in 2001 First patient treatment foreseen in 2007 Rome SB - 5/5 42

43 The TERA Foundation Not-for-profit foundation created in 1992 by Ugo Amaldi and recognized by the Italian Ministry of Health in 1994 Research in the field of particle accelerators and detectors for hadron-therapy First goal: the Italian National Centre (CNAO) now under construction in Pavia Ugo Amaldi Rome SB - 5/5 43

44 CNAO on the Pavia site Main source of funds: Italian Health Ministry Ground breaking: March m PIMMS/TERA Hospital based centre Design Protons and carbon ions Rome SB - 5/5 44

45 CNAO synchrotron hall in March 2007 Courtesy Sandro Rossi, Fondazione CNAO Rome SB - 5/5 45

46 Neutrons in cancer therapy Rome SB - 5/5 46

47 Hadrontherapy with fast neutrons Berkeley, 1938 Neutrons are neutral no Bragg peak MeV neutrons are produced with cyclotrons (p + Be reaction) MeV neutrons produce nuclear interactions high LET radiation Used for radio resistant tumours (ex. salivary glands, tongue, brain) About 9 centers in the world [ex. Orleans (France), Fermilab (USA)] Rome SB - 5/5 47

48 Boron Neutron Capture Therapy (BNCT) Concept proposed in 1936 by G.L. Locher (only 4 years after the discovery of the neutron!) Bring into cancer cells a nuclide that captures neutrons and disintegrates into high LET fragments 10 B is used Available (20% of natural B) Fragments of high LET and path lengths approximately one cell diameter (about 12 microns) Well known chemistry Rome SB - 5/5 48

49 BNCT facilities Nuclear reactors or accelarators are used as sources of epithermal neutrons Many centers in the world, mostly for clinical trials Limitation Difficult to achieve selective localization in the tumour! Rome SB - 5/5 49

50 End of part V Rome SB - 5/5 50