1. Protontherapy at INFN-LNS C.Agodi Laboratori Nazionali del Sud - Catania LEA-COLLIGA – IPN Orsay November 14-16 2011

2. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

3. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

4. LNS LNS Depth dependence of the deposited dose for different radiation Why clinical hadron beam? Higher precision and greater biological effectiveness of the applied dose Because of the Bragg peak, protons dose distribution is “inverted” with respect to the almost exponential behaviour produced by a beam of high energy photons. The surface dose is low when compared to the dose absorbed in the region of the peak, at variance with what happens with photons and electrons.

5. penetration depth is well-defined and adjustable most energy at end-of -range protons travel in straight lines dose to normal tissue minimised no dose beyond target PROTONS PERMIT TO DELIVER AN HIGH DOSE TO THE TUMOUR SPARING THE SOURRONDING TISSUES Why clinical proton beam?

6. Between the eyes Intensity Modulateted Radiation Therapy vs PROTONS Abdomen Brain

7. PT faces a fast growing demand! PT center under operation LNS LNS 1954 - C.Tobias and J.Lowrence: first therapeutic exposure of human patients to hadron beams at the Radiation Laboratory of California, Berkeley 1957 – Protons treatments : University of Uppsala, Sweden 1961 – Massachusetts General Hospital-Harvard Cyclotron Laboratory,USA 1967 – Dubna, 1969 Moscow, 1975 St Petersbourg in Russia 1979 – Chiba, 1983 Tsukuba in Japa 1984 – PSI-Villigen in Switzerland 1990 - The Loma Linda University Medical Centre in California heralded the age of “dedicated” medical accelerators with commissioned its proton therapy facility with a 250 MeV Synchroton

8. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

9. In 90’ years INFN supported TERA in R&D project. INFN, in collaboration with University of Catania, realized in its laboratory (Lab. Naz. Del Sud) the first Italian protontherapy facility. INFN has UNIQUE capability in Italy in accelerators development. Considering its particular features, INFN was involved in CNAO to guarantee the necessary expertise. In 2005 INFN was encharged by Health Minister to produce a document about protontherapy in our country. INFN & Hadrotherapy

10. In Catania we developed a facility (named CATANA) for the treatment of ocular tumours with 62 AMeV proton beams

11. LNS Superconducting Cyclotron is the unique machine in in Italy and South Europe used for protontherapy Treatment of the choroidal and iris melanoma In Italy about 300 new cases for year

12. CATANA LNS Accelerator Layout Ocular Protontherapy Unique Italian Facility

13. CATANA proton therapy beam line ( until June 2004 )

14. CATANA proton therapy beam line ( new location )

15. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

16. Scattering system Modulator & Range shifter Monitor chambers Ligth field Laser CATANA proton therapy beam line

17. Lateral dose distribution in a clinical proton beam 95 % 50 % 20 %

18. Depth dose distribution – Energy modulation Generation of the Spread Out Bragg Peak (SOBP)

19. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

20. Absolute Dosimetry: Energy Released in Water (Gray) Relative Dosimetry: Three dimensional dose distribution measurements  Considering the high gradient dose, conformation and small fields often used the detectors have to be kindly characterized in terms of spatial resolution, energy or fluence dependence to be used in protontherapy. Dosimetric commissioning: absolute & relative dosimetry Relative and Absolute Dosimetry are fundamental for: Customizing of TPS Monitor Unit Calculation Quality Control

21. ICRU 59 AND TRS 398 IAEA RECOMMENDATION  “ FOR MEASUREMENTS OF DEPTH-DOSE DISTRIBUTION IN PROTON BEAMS THE USE OF PLANE-PARALLEL CHAMBERS IS RECOMMENDED”  Parallel plate MARKUS PTW is the golden standard for depth dose measurements Dosimetric commissioning: absolute & relative dosimetry

22. Monte Carlo Simulation of the entire beam line using GEANT4: Improvement of our beam line and dosimetry Give a general purpose tool for the design of new hadron- therapy beam line Validation of the treatment system software GEANT4 simulation GEANT4 Simulation

23. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

24.  The Surgical Phase  The Treatment Planning Phase  The Verification Phase  The Treatment Phase A typical treatment

25. Two orthogonal X-Rays tubes for the visualization of the clips

26. name@mail.com26 Lay-out of the axial X-Ray flat panel with its moving system Hamamatsu X- Ray axial flat panel NEW X-RAY SYSTEM FOR PATIENTS POSITIONING

27. EYEPLAN Originally developed by Michael Goitein and Tom Miller (Massachussetts General Hospital), is now maintained by Martin Sheen (Clatterbridge Center for Oncology) and Charle Perrett (PSI) Treatment Planning System Phase

28. This point is chosen in order to spare the organs at risk, and to maintain the best polar angle. Fixation Point Choice

29.  Fixation Light   Polar Angle  Azimuthal Angle Isocenter Fixation Point

30. Isodoses curves for different planes Treatment Planning System Output

31. At the end of patient positioning phase the radiotherapist draws the eye’s contour on a dedicated monitor in order to monitoring in any moment the eye’s position during the treatment. Dose: 15.0 CGE per day Fractions: 4 Treatment Time: 45-60 sec. Total Dose: 60 CGE Treatment Phase TREATMENT MODALITIES

32. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Clinical results 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

33. Patient Distribution by Pathologies Uveal Melanoma 164 patients Conjunctival Melanoma4 patients Conjunctival rhabdomyosarcoma 1 patient Eyelid Carcinoma and metastases 2 patient Conjunctival MALT-NHL1 patient Conjunctival Papilloma2 patient TOTAL PATIENTS 174

34. 70 29 10 18 7 3 10 3 1 2 Total number of patients : 230 Since feb 2002 Patient Distribution by Origin Region 2 1

35. Patient Distribution by Sex The patients’age ranges between 14yrs and 81yrs (the mean age is 48 yrs)

36. PatientsTotal Number (April 2009) 174 Patients with Follow up138 TUMORAL THICKNESS ECOGRAPHIC REFLECTIVITY Reduced 70 % Increased77 % Stable24 %Stable18 % Increased2 %Not evaluable5 % Not evaluable2 % PATIENTS FOLLOW-UP (March 2002 – November 2008)

37. SURVAIVAL RESULTS PatientsTotal Number (April 2009) 174 Dead patients4 Metastatis3 Other1 Eye retention rate95 % TOTAL SURVIVAL98 % LOCAL CONTROL95 %

38. 2. INFN & HADRONTHERAPY: THE CATANA PROTON THERAPY CENTER Beam line elements The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry Treatment procedure Patient’s follow up 3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF OUTLINEOUTLINE 1. Why proton beams in tumour radiation treatment

39. CATANA Spin-off: Some Important Milestones In 2002, the First Italian Protontherapy Facility Funded by INFN and Catania University started in Catania at INFN-Laboratori Nazionali del Sud Sicilian Region has approved to realize an HadronTherapy Center in Catania, for protons and heavy charge particles. It has to be realized as “Scientific collaboration between Region, INFN and University of Catania also open to private contributions”

40. What is in progress? Proton computed tomography (PCT) Carbon beams for therapy… Lithium beams for therapy? …….

41. Remarks Knowledge gained from basic research influenced the choices of ion, energy, beam delivery system and treatment schedule. Moreover radiotherapy shall be developed only on the basis of research conducted according to the highest standard of scientific inquiry and using the most advanced method available.