Particle Therapy at GSI

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Presentation transcript:

Particle Therapy at GSI C. Graeff GSI Biophysics

GSI Helmholtz Center for Heavy Ion Research Budget: ~100 M€ Employees: 1350 incl. scientists & engineers: 750 Darmstadt Visiting scientists: 1000 Cave M Large facility equipment: accelerators and experiments 1998 – 2008: pilot project of scanned ion therapy

Towards FAIR GSI FAIR Research continues „FAIR Phase 0“ regular beam from 2018 on (SIS18) GSI FAIR Future Beams: Intensity: primary HI 100-fold secondary RIB 10000-fold Species: Z = -1 – 92 (anti-protons to uranium) Energies: ions up to 35 - 45 GeV/u antiprotons 0 -15 GeV/c Precision: full beam cooling April 2014

Physics research questions Basic components of matter Why don‘t we observe free quarks? Why are protons and neutrons much heavier than their components? Which combination of protons and neutrons gives stable nuclei and what are properties of non-stable nuclei? What are basic symmetries existing in nature and which physics laws do they reflect?

Physics research questions Evolution of the universe What came after the Big Bang? Can we create quark-gluon pasma in heavy ion reactions? Which nuclear reactions are taking place during nuclear fusion? What is the role of non-stable nuclei in fusion? In which state occurs nuclear matter under high temperature and pressure? What is so called dark matter? Why is our universe from matter and not from antimatter? Can we learn more about symmetry breaking in the universe?

One example – CBM experiment 30/08/2017 Chania Workshop on Ions ...

The Biophysics department 8 subgroups from basic biology to applied medical physics G. Taucher-Scholz (DNA repair) M. Krämer (physical modeling) S. Ritter (chromosome aberrations) C. Graeff (medical physics) C. Fournier (tissue effects) U. Weber (radiation physics) M. Scholz (biological modeling) Department lead currently vacant (until 2015: M. Durante) Interim joint directors: M. Scholz & C. Kausch

Tumor therapy with scanned carbon ion beams 1 . 2 8 6 4 Tumor Normal tissue Relative dose Durante & Loeffler, Nat Rev Clin Oncol 2010 Potential advantages of heavy ions Depth (mm) High tumor dose, normal tissue sparing Effective for radioresistant tumors Effective against hypoxic tumor cells Increased lethality in the target because cells in radioresistant (S) phase are sensitized Fractionation spares normal tissue more than tumor Reduced angiogenesis and metastatization Energy LET Dose RBE OER Cell-cycle dependence Fractionation Angiogenesis Cell migration high low low high low high  1 > 1  3 < 3 Increased Decreased Tumor therapy with scanned carbon ion beams 28.04.2014

Tumor therapy at GSI – Cave M 1997 – 2008: 440 patients treated, mainly chordoma & chondrosarcoma of the skull Project partners: GSI, Radiooncology Clinic and DKFZ in Heidelberg, Helmholtz Center Dresden/Rossendorf (former FZR) Succeeded in 2009 by Heidelberg Ion Beam Therapy Center (HIT)

Therapy developed at GSI Accelerator control 255 energies, 7 foci, 15 intensities – different in each spill Beam monitoring Precision dose application: PPIC and MWPC still in use today Positron emission tomography: beam range Beam scanning First clinical use of full 3D active energy scanning at GSI Radiobiology & biological modeling local effect model (LEM I - IV) Treatment planning software (TRiP)

Rasterscanning Haberer et al. 1993

Scanned beam examples / CR-39 stack [M. Krämer, U. Weber, GSI and Phys. Med. Biol. 2000]

The treatment plan - example [M. Krämer, U. Weber, GSI and Phys. Med. Biol. 2000]

Current version: LEM IV The Local Effect Model Current version: LEM IV Slightly different modeling approach Supports multiple particles Proton RBE! LEM I in clinical use in Siemens Syngo TPS Heidelberg, Marburg, Pavia, Shanghai LEM IV licensed to RaySearch Will be used at MedAustron Main investigator: Michael Scholz

Relative Biological Effectiveness RBE [Krämer et al. and Weyrather et al., GSI] Linear Energy Transfer ~ stopping power Modeling required to determine RBE!

Basis of the local effect model Local Dose [Gy] Photons Tracks Cell Cell nucleus Carbon ions Local Dose [Gy] x10000 Carbon ions, local Local Dose [Gy]

Local Effect (Photons) = Local Effect (Ions) Local Effect Model LEM Basic Assumption: Increased effectiveness of particle radiation can be described by a combination of the photon dose response and microscopic dose distribution Local Effect (Photons) = Local Effect (Ions) + RBE ! LEM: Transfer of low-LET experience to high-LET

Depth Dependence of RBE RBE weighted Dose [Gy]

Positron Emission Tomography Collaboration under lead of Forschungszentrum Dresden-Rossendorf (Wolfgang Enghardt) Starting with re-unification funds in the 90ies

Range uncertainties (Mostly) controllable for regions with defined bone structure: ~ 1 mm in head & neck range dose photons 12C [S.O. Grözinger, GSI] Much more difficult in chest / abdomen: deformable tissue, breathing & heart beat

Bragg curve – fragment contribution

Loss of initial particles Some projectile fragments are positron emitting isotopes, e.g. 11C and 10C (half-lifes: 20 min and 20 sec) Can be used for Positron Emission Tomography (PET) [E. Haettner, MSc-Thesis]

PET-control of treatment projectile target [Enghardt et al. Rossendorf] Tumor therapy with scanned carbon ion beams 28.04.2014

Dose verification with PET 3D reconstruction by back projection Positron emitter distribution neither proportional nor equivalent to the dose distribution Comparison with expected positron emitter distribution Treatment plan Predicted b+-activity Measured b+-activity [Enghardt et al. Rossendorf]

Clinical outcome of the pilot project Photons Protons + Photons Carbon Ions 100 Local control (%) overall 10y-local control: 88% 50 100 150 200 Time from irradiation (month) Chondrosarcoma Chordoma Schulz-Ertner et al., IJROBP 2007 Uhl et al., Cancer 2014

Future research topics FAIR-specific Space irradiation (C. Schuy, Tuesday) Particle imaging / theranostics (M. Schanz, Wednesday) Tissue-level effects / adverse events Radio-Immunology Licensed for human stem cells Radiotoxicity in embryonal development Radiotoxicity for neuronal / cardiac tissue Different ion species: He, O Effect-based optimization: Kill painting Moving targets (C. Graeff, Wednesday)