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Institut Curie – CPO and France programs Annalisa Patriarca on behalf of the Institut Curie –

Institut Curie – CPO and France programs Annalisa Patriarca on behalf of the Institut Curie – Centre de Protonthérapie d’Orsay team. Status and future perspectives of charged particle therapy, 17 – 18 December 2013, Fondazione CNAO. Plan.

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Institut Curie – CPO and France programs Annalisa Patriarca on behalf of the Institut Curie –

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  1. Institut Curie – CPO and France programs Annalisa Patriarca on behalf of the Institut Curie – Centre de Protonthérapie d’Orsay team Status and future perspectives of charged particle therapy, 17 – 18 December 2013, Fondazione CNAO 1 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  2. Plan • Presentation of the Institut Curie and of the Proton therapy center in Orsay (IC – CPO) • IC – CPO clinical program • IC – CPO involvement in physics and radiobiology research • IC – CPO experimental plan 1 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  3. Institut Curie: a dedicated cancer center working on treatment, and basic, translational, clinical research • Hospital Group • Paris Hospital • Proton therapy center in Orsay (IC - CPO) • René-Huguenin Hospital in Saint-Cloud • Research Center • 15 units (>1000 person) in Paris and Orsay • which are associated with universities and the • French national research centers (CNRS, • Inserm). • Translational Research Department • scientific innovations to improve patient care • preclinical studies for cancer understanding René-Huguenin Hospital Paris Hospital Paris Area Orsay Proton therapy Center 2 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  4. The Radiation Oncology Department • Radiation therapy facility of the Institut Curie Hospital (Paris, Orsay, St Cloud): • 9 linear accelerators • 4 high-dose-rate and pulsed-dose-rate brachytherapy systems • Brachytherapy by 125 Iodine plaque and seeds • 2 simulators-scanners   • 2 dedicated scanners for scanography • 2 tomotherapy machines   • 1 cyclotron with 3 proton treatment rooms (IC - CPO Orsay) • Around 4900 patients treated per year • 10% with Proton therapy 3 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  5. IC – CPO team organization 20 Therapists and Dosimetrists 14 Technicians and Engineers 4 MedicalDoctors 6 Medical Physicists 4 IBA on site team Operation Tests and QA Maintenance R&D

  6. Important milestones in the IC – CPO history • 1957: 1st French synchrocyclotron (160 MeV) in Orsay • 1975 - 1979: Recasting of the synchrocyclotron (201 MeV) • 1987 - 1989 : Modifications of equipment and building for medical treatments • 1991 : 1st ophthalmological treatment • 1993 : 1st head & neck treatment • 2004 : Integration to Institut Curie • 2004 - 2010 : Expansion Project (new cyclotron + 1 gantry) • July 2010 : 1st treatment with new cyclotron • 26 Oct 2010 : 3rd treatment room (gantry) opened More than 6000 patients treated since 1991 5 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  7. IC – CPO : 1991 – April 2010 • First room opened : • Chair treatment • ophtalmology • head & neck • Second room opened : • Couch or chair treatment • head&neck 6 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  8. 1sttreatment room • Eye treatments • 300 patients/year • Choroidal Melanomas: 87% • Conjunctival Melanomas: 5% • Choroidal Hemangiomas: 4% • Iris Melanomas: 2% • Others: 1% • Hypofractionation: • 4 fractions of 15Gy/w • 8 fractions of 7.5Gy/2w • TPS: EYEPLAN • Imaging system: Hamamatsu flat panel • Alignment system: Dispot software • Robotic positioner 7 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  9. 2nd treatment room • Head & neck treatment since 1996 • Supine or seated treatment positions • Treatment capacity : 14 patients/day • Conventional fractionations of 1.8Gy 5days/w • TPSIsogray • Imaging system • Dicom imaging system • Flat panel sensor + CPO acquisition software • Patient alignment system (Rotaplus) • Fiducial markers (anatomical in development) • Pair of orthogonal images • Automatic correction matrix sent to positionner 8 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  10. ESS Y1 Head&neck treatments (201 MeV) Existing IC - CPO Momentum slits Dégradeur PY1 Continuous energy selection between 70MeV and 230.67 MeV Connection point P2 PY2 C235 Y2eye treatments (76 MeV) and Head&neck treatments (201 MeV) • Gantry • Universal Nozzle: • Double Scattering • Uniform Scanning • Pencil Beam Scanning IBA equipment IC – CPO since 2010 9 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  11. (IBA source) SIS => Y2 DS => Y1, GTR US => GTR PBS => GTR 11 10 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  12. Gantry room: open October 2010 • 15 patients/day: • Head&neck (Pediatric with anestesia) • Spine • Sacrum • Field size: • circular collimators: from 2 to 22 cm • rectangular collimator: 30cm x 40cm • Forte robot (industrial Kuka robot) : • Isocentric motion (+/- 0.5 mm (1σ)) inside • treatment volume • 6 DOF : pitch & roll (+/- 15°) • Alignment system • Verisuite software • Patient survey system: Medusa Credit : Eric Bouvet / Institut Curie 11 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  13. Workflow (intracranial) 1st Consultation TPS Protons Simulation Proton Fields Milling QA markers implantation IRM+TDM Tumor contouring 1 Week 4 Weeks W - 2 W - 1 D - 4 D - 2 7 Weeks 12 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  14. Workflow (ophtalmic) 1st Consultation Echography Markers implantation TPS Protons Simulation Proton Fields Milling QA W-3 W-2 D-10 D - 1 D - 1 D - 1 D - 1 3 Weeks 13 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  15. Plan • Presentation of the Institut Curie and of the Proton therapy center in Orsay (IC – CPO) • IC – CPO clinical program • IC – CPO involvement in physics and radiobiology research • IC – CPO experimental plan 14 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  16. Actual clinical indications at IC – CPO • Adult tumors • Eyes tumors (Melanoma, hemangioma) • Chordoma, Chondrosarcoma • Meningioma (malign. atypic. Intraorbit.) • Sacrum sarcoma • Pediatric tumors • Craniopharyngioma • Rhabdomyosarcoma • Ependymoma, Medulloblastoma, Low Grade Glioma • Other CNS Tumors (Germ Cell Tumors, PNET…) • Base of Skull tumor (chordoma) • Sacrum sarcoma 15 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  17. IC – CPO clinical program 16 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  18. Intra-Cranial Tumors - Ratio Pediatric/Adult 11 12 IC – CPO clinical program 17 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  19. IC – CPO clinical program: PencilBeam Scanning • More clinical possibilities • Treatment quality enhancement IMRT Protons IMPT 18 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  20. IC – CPO clinical program • Development of new clinical protocols combining chemotherapy and radiation therapy • Moving tumours (liver, lung) • Hypo fractionation • IGRT • RT adaptative 19 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  21. IC – CPO clinical program and real life Sessions vs unexpected events at ICPO (and expectations) Damage on the guidance system of the ion source (left) and stripe on the shaft (right) Damage on deflector insulator 20 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  22. Plan • Presentation of the Institut Curie and of the Proton therapy center in Orsay (IC – CPO) • IC – CPO clinical program • IC – CPO involvement in physics and radiobiology research • IC – CPO experimental plan 21 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  23. IC – CPO developments programs • TPS • OIS • Imaging and positioning 22 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  24. CI 1 C1 CI 3 C4 C4 C2 C3 CI 2 C5 Fantôme d’eau Water Modulator Modulateur Range Range Shifter shifter Scatterer diffuseur Concrete shield Blindage shield Nez Telescopique Telescopic Nozzle Blindage en béton TPS developments: from double scattering to pencil beam scanning • 1995-2008: Development of in-house TPS with DS and US algorithms for horizontal and gantry beam lines (ray tracing, pencil beam, DRR, compensators). • 2008-2012: Use of Monte Carlo simulations (MCNPX): monitor units predictions, secondary neutron doses, TPS benchmarking. • 2013-2014: Installation of PBS (IBA universal nozzle), analytical models for pencil beam scanning, with superposition of elemental pencil beams and IMPT developments (gradient optimization). 23 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  25. OIS: from prescription to dose measurements • R&V for horizontal treatment rooms and gantry 24 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  26. Imaging and positioningdevelopments • Image registration without fiducial markers both in gantry and in the horizontal treatment rooms • Improving positioning accuracy (robot coupled with Polaris system) • Motion detection in the patient survey system 25 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  27. The IC-CPO involvement in national research programs: Physics PROUESSE Project: PRotontherapie développement et validation d’un OUtil de modélisation Et Simulation monte carlo précises et rapides du dépôt de doSE MCNPX modélisation de la ligne MCNPX beamline modellization 26 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  28. The IC-CPO involvement in national research programs: Physics SAPHIR: Accelerated Proton Source by High Intensity laser for Radiotherapy • Partnership between 10 companies/laboratories to prove the technologic and economic viability of the Plasma Laser for the protontherapy • The ICPO part is: • - the medicalization of the proton beam • - the radioprotection of the building • 2013: 34 MeV LOA, mesurements/Monte Carlo on the laser plasma beamline 27 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  29. The IC-CPO involvement in national research programs: Physics (CNRS - CEA) • 2012 - : CNRS (centre d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) - Laboratoire de Physique Corpusculaire (LPC) Clermont Ferrand and CEA (SHFJ) collaboration • Dose on linemonitoring • PMMA phantoms irradiation with a 86.8 MeV proton beam (4 Gy at Bragg peak) + detection blocs: • Monte Carlo (GATE) validation for range determination in antropomorphic phantoms • Detectors for the on line monitoring • PET- based dose monitoring for proton therapy: preliminary assessment of the influence of an • accurate beam modeling on the simulated β+ activity spatial distributions. C. Robert et al. • PTCOG52 2013 28 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  30. The IC-CPO involvement in national research programs: Radioprotection (IRSN) 1) Monte Carlo modelisation of the treatment rooms (i.e secondary particle cartography) 2) Simulations and measurements of the dose due to secondary neutrons during a pediatric proton therapy treatment • Estimation des doses dues aux neutrons secondaires reçues par les patients en protonthérapie : cas des traitements ophtalmologiques. F.Martinetti, Phd thesis, 2009 • Monte Carlo simulation of a proton therapy beam line dedicated to intracranial treatments, R.Sayah, Phd thesis, 2012

  31. The IC-CPO involvement in national research programs: Radiobiology (IC – Research department) • RBE caracterisation for proton beams of 76MeV and 201MeV : cell type and SOPB position dependence • Projects: • RBE dependence on high dose rates • RBE, repair mechanisms and signaling pathways activated following conventional dose-rate protons vs. X-rays • Radiobiological characterization of two therapeutic proton beams wit h different initial energy • spectra used at the Institut Curie proton therapy centre in Orsay, V. Calugaru, Phd thesis, 2011 30 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  32. IC-CPO collaborations: a special one • From 1998 - : INFN and INFN spin off (De.Tec.Tor) • TERA chip technology MOPI pixel chamber • MLIC multi leaf ionization chamber 31 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  33. Plan • Presentation of the Institut Curie and of the Proton therapy center in Orsay (IC – CPO) • IC – CPO clinical program • IC – CPO involvement in physics and radiobiology research • IC – CPO experimental plan 32 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  34. Institut Curie development of an experimental radiation biology facility • A dedicated experimental room • proton beam (230 MeV max energy) • pencil beam scanning available • Two new animal X-ray generators • a basic X-rays generator (320 kV) • a small animal image guided radiation research platform • Dedicated animal care facility (level 2) • Cell culture laboratory (level 2) • A level 1 laboratory • preparation of tissue samples • Storage room, offices 33 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  35. Development of the experimental radiation biology facility • IC – CPO involvement • Availability of a dedicated beam line to not interfere with the clinical activity • Preparation room • Support in radiobiology experimental studies, physical research and clinical research • Development of specific devices for in vitro and in vivo radiation biology experiments • Ability to conduct full animal experiments 34 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  36. Experimental room (preliminary studies) Deviation Shielding Beam line 35 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  37. Integration of a preparation room for the users Hotte chimique Stockage Paillasse 5 Portoir cages Stabulation/DASRI 168 324 Congélateur Expérimentation animale contention Paillasse Double paillasse Paillasse 1 Paillasse 2 352 Pièce de culture cellulaire Etuves 324 Paillasse Paterre Paillasse PSM telstar Microscopie 3 4 Paillasse 36 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  38. IC – CPO involvement in France Hadron consortium • FRANCE HADRON - a national infrastructure distributed on 5 nodes : • ETOILE Center in Lyon, • ARCHADE Center in Caen, • Centre Antoine Lacassagne / IMPACT in Nice, • Curie Institute / ICPO in Orsay, • Claudius Regaud Institute / PERICLES in Toulouse. • with the partnership of CNRS/IN2P3 (IPNL & LPC) and of IRSN, and the support of INSERM, INCa, CEA, ENLIGHT, ULICE and 16 industrials et public institutions including CNES, Thales, Mérieux... • FRANCE HADRON objectives • To optimize technical means and procedure for hadrontherapy • To federate and organize national research • To build new research beam lines for protons and carbon ions • To fund beam time and beam line access for research 37 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  39. France Hadron scientificproject

  40. IC – CPO involvement in France Hadron consortium • IC – CPO as irradiation platform: • 300 hours/year for experiences with external users • Dedicated proton experimental room at the IC – CPO • Dedicated room for the users • Commissioning of 200 MeV proton beam in the ophthalmic treatment room to make experiences even without the dedicated room 39 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  41. IC – CPO involvement in France Hadron consortium • First experiences in the frame of France Hadron • 2013 (200 MeV): collaboration with CNRS – centre d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC) – et l’Institut des sciences moléculaires d’Orsay (ISMO) • Project: investigations on the enhancement of the therapeutic index in proton therapy by using nanoparticles • Irradiations in vitro et in vivo 40 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  42. IC – CPO programs conclusions • Clinical: increase the activity, enhance its quality and diversify the localisations • Improving the patient workflow • Reliability of the system as high as possible • PBS treatments • Research: • Involvement in France Hadron • Support for the radiobiology platform of the Institut Curie • Continuity of the collaboration with universities, national research institutes, and industrial companies 41 - A. Patriarca, Institut Curie – CPO and France programs, 17 - 18 December, Fondazione CNAO

  43. Hadrontherapy France 2012 Orleans Neutrontherapy 1980-1991: 2000 pats Orsay Protontherapy LE&HE 1991- … 5949 pats Nice Neutrontherapy 1993-1995: 60 pats Protontherapy LE 1991- … ~ 4692 pats Lyon Protons + Carbon ? 201X? Caen Protons + R&D C ? 201X? Toulouse Protontherapy 201X? Announced in meeting

  44. THANK YOU FOR YOUR ATTENTION http://protontherapie.curie.fr/ 43 – A. Patriarca, Institut– CPO and France programs, 17 - 18 December, Fondazione CNAO

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