Particle Accelerators for Medicine in North America (USA and Canada)

Transcription

1 Particle Accelerators for Medicine in North America (USA and Canada) IoP/STFC Workshop on Particle Accelerators for Medicine Franklin Theatre Institute of Physics, London February 17, 2015 Swapan Chattopadhyay

2 OUTLINE Cancer Therapy and Particle Beam Requirements Particle Beam Therapy in US: History and Current Industrial vendors and what are they delivering What s new in accelerator technology for cancer treatment? Developments in CANADA: Medical Isotopes Outlook in US

3 Acknowledgments Thomas Kroc (Fermilab) David Robin (Berkeley Lab) Sami Tantawi (SLAC) Dejan Trbojevic (BNL) George Coutrakon (NIU) Paul Schaefer (TRIUMF)

4 Charged Particle Accelerators for Radiation Therapy Charged Particles of interest for therapy: Protons and other light ions (He 2+, C 6+, O 8+ ) Types of accelerators in use: Synchrotrons, Cyclotrons and Synchro-cyclotrons Recent interest in electrons Types of accelerators in use: direct use of electrons from electron linear accelerators Neutrons used in the past, rapidly diminishing interest due to collateral damage X-rays for use in radiation therapy Types of accelerators in use: electrons from linear accelerators producing collimated x-ray beams via bremsstrahlung from stoppage in an internal target I WILL NOT ADDRESS X-RAYS IN THIS TALK.

5 Dose vs. Depth in patient for various Radiation Fields (x-rays, protons, electrons) 50 to 250 MeV is clinical range of interest for protons Eye Tumors at 50 MeV; Prostate Tumors at 250 Proton Energy vs Range in Tissue Range (cm) Energy (MeV) Series1

6 Light ions ( He, C, O) have a larger biological Bragg peak and higher peak to entrance ratio

7 Light ions scatter less in tissue ; sharper dose fall off on lateral edge of tumor

8 Are Carbon ions better than protons? In Theory, Yes! Target dose/entrance dose higher compared to protons, but in vivo RBE s not as well known as protons. Therefore damage to healthy tissue not as well known. Sharper dose edges/dose conformity, in target than protons. Japanese treat Lung tumors with 2 to 3 Carbon treatments compared to 10 or 20 in the US. Only 10,000 patients have been treated with Carbon ions, compared with 100,000 proton/10 s of millions x-ray patients. There are no randomized trials or other evidence that suggests outcomes are better with Carbon. Carbon has 3 times the rigidity of Protons for the same range in tissue, hence larger size, more $$$, (20 meter diameter accelerator as opposed to 6 or 7 for Bmax =18 KG), difficult to make gantry no practical gantries demonstrated, though much R&D currently. No FDA clearance no reimbursements, and even with FDA, reimbursements will likely be at proton rates.

9 Accelerator requirements for cancer therapy Energy range; MeV P+, MeV/amu C 6+ Dose rate: 1 to 2 Gray per minute per liter of tissue Rule of thumb: 10 9 P/cm 2 /Gray for 5 to 10 cm SOBP 20 cm x 20 cm field size and 40% beam usage, need P/min or 3 na to get 1Gray/min (approximately) Rapid beam energy changes; E < 5 MeV in 1 to 2 sec Small beam emittance 1-3 π mm-mrad ( 67% of beam) Small foot print for cost control Low power consumption ( 100 to 300 kw) Low maintenance and ease of access Low neutron exposure to personnel/low equipment activation Small enough to fit on a gantry which can rotate around patient?

10 HISTORY of LABORATORY ACCELERATOR-BASED MEDICAL RESEARCH and THERAPY (USA) Laboratory Type of treatment Years operational # of patients treated FNAL Neutron Therapy > 3000 very little 'research' after mid-80's LANL Negative pion therapy Berkely Proton therapy Berkeley 184" Cyclotron - p & He? >1000 Berkeley Bevalac - ions Harvard Cyclotron Lab Proton therapy >9000

11 10 Facilities in operation in USA in more (not shown) since then from Central Dupage Hospital MPRI MGH - Boston Univ. of Pennsylvania Hampton Univ. Loma Linda Univ. Medical Center Barnes Hospital Oklahoma City M Univ. of Florida Scale Legend recently operational MD Anderson Existing Site before 2010

12 HOSPITAL-BASED PARTICLE BEAM CANCER THERAPY FACILITIES (USA) S/C/SC* START COUNTRY WHO, WHERE PARTICLE MAX. ENERGY (MeV) BEAM DIRECTIONS OF TREATMENT TOTAL PATIENTS TREATED DATE OF TOTAL USA, CA. J. Slater PTC, Loma Linda p S gantries, 1 horiz Dec USA, CA. UCSF, San Francisco p C 60 1 horiz Dec USA, MA. MGH Francis H. Burr PTC, Boston p C 235 USA, IN. IU Health PTC, Bloomington p C 200 USA, TX. MD Anderson Cancer Center, Houston p S 250 USA, FL. UFPTI, Jacksonville p C 230 USA, OK. ProCure PTC, Oklahoma City p C gantries***, 1 horiz. 2 gantries***, 1 horiz. 3 gantries***, 1 horiz. 3 gantries, 1 horiz. 1 gantry, 1 horiz, 2 horiz/60 deg Sep Dec Closed Dec Dec Dec

13 HOSPITAL-BASED PARTICLE BEAM CANCER THERAPY FACILITIES (USA), cont d USA, PA. Roberts PTC, UPenn, Philadelphia p C 230 USA, IL. CDH Proton Center, Warrenville p C 230 USA, VA. HUPTI, Hampton p C gantries, 1 horiz. 1 gantry, 1 horiz, 2 horiz/60 deg. 4 gantries, 1 horiz Dec Dec Dec USA, NY. USA, WA. USA, MO. USA, TN. ProCure Proton Therapy Center, New Jersey SCCA ProCure Proton Therapy Center, Seattle S. Lee Kling PTC, Barnes Jewish Hospital, St. Louis Provision Center for Proton Therapy, Knoxville p C gantries Dec p C gantries Dec p SC gantry Oct p C gantries Aug USA, CA. Scripps Proton Therapy Center, San Diego p C gantries, 2 horiz Dec USA, LA. Willis Knighton Proton Therapy Cancer Center, Shreveport p C gantry Dec

14 The accelerator foot prints are small, but not small or light enough to mount on a gantry or fit in pre-existing treatment room

15 LLUMC Proton Synchrotron

16 Synchrotrons

17 Particle Therapy Vendor List (Mevion below and Varian 250 MeV cyclotron are Superconducting machines)

18 Mitsubishi 250 MeV Synchrotron 2-3 accelerators in Japan and 2-3 more under construction Currently used for passively scattered beams only Not currently being sold in the US

19 Heidelberg Heavy Ion Facility and Accelerator (offered by Siemens) Accelerator can accelerate 4 ions Protons, Helium, Carbon, and Oxygen nuclei Particle range in tissue > 30 cm Accelerator uses 256 energies, 15 intensities 6 spot sizes ( 4 to 10 mm) Accelerator gating for respiration is an option Spill duration and cycle times are driven by Tx planning optimization

20 230 MeV Proton Cyclotron offered 8 cyclotrons delivered in US, 4-5 Asia, more under construction. FDA approved for passive delivery and scanning in US Compact design in 4 meter diameter Beam losses on steel of magnet 50 to 60 % and requires energy degrader by IBA of Belgium

21 Mevion 250 MeV superconducting cyclotron, 20 Ton, 1.8 meter diameter, 9 Tesla magnet Full system installed and tested ( with FDA clearance) in 2012 at Barnes Jewish Hospital in St. Louis, MO 1 st patient treatments expected by end of 2013

22 ProTom 330 MeV proton synchrotron

23 Varian SC 250 MeV Proton Cyclotron Superconducting low power (only 40KW for Cryostat + RF ) Higher energy beam, 37 cm penetration in water, vs. 32 cm (IBA) Higher extraction efficiency, 80%, vs. 40% for IBA less radioactivity during maintenance Three units delivered; PSI (Switzerland), Munich, San Diego, CA

24 Hitachi Proton Therapy Synchrotron 7 MeV multi-turn injector Uses RF knockout for fast beam on/off during spill Uniform intensity (+/- 15%) to patient Dose rate = 2 Gy/min with FS = 25 x 25 cm 2 accelerators in use, 2-3 more on order. FDA approved in USA

25 Vendor Activity Score IBA/ Procure Mitsu -bishi Varian Hitachi Sumitomo Siemens Complete and Built Complete In Prog. Partial Systems ? 2?

26 NEW DIRECTIONS Compact Superconducting Gantry (BNL and LBNL) FFAGs (Kyoto, FNAL, UK) Dielectric Wall Accelerator (LLNL) PHASER: direct use of electrons (SLAC) Ions from Laser-irradiated Foils (contamination a big issue, I WILL NOT ADDRESS THIS IN MY TALK)

27 Heidelberg Carbon ion gantry with beam scanning: too large, complex and heavy!! 600 tons, 13 meter diameter and 25 meter length approx. 7 x size of LLUMC gantry ( 90 tons) Operational since about 2010 Simplifying the GANTRY is a MUST!!

28 Demanding Requirements: Compact gantries Work done at BNL (compact gantries) : Dejan Trbojevic Work done at LBNL (compact superconducting gantries): David Robn and Shlomo caspi High Field Large High Bending Field Angle (90 ) Large Large Aperture Bending (20 Angle x 20 cm) (90 ) Combined Large Aperture Function (20 Fields x 20 cm) (large Combined SAD and Function small distortion) Fields Rotatable (large SAD (up to and 360 ) small distortion) Fast Rotatable Ramp Rates (up (up to 360 ) to 1 T/s) Fast Ramp Rates (up to 1 T/s) Large Aperture Curved Canted Cosine Theta (CCT) Magnet Curved Helical Quadrupole Focusing Channels

29 Start with Pavlovic Type Gantry Design Direction Direction 1: 1: Reducing the size of the Final 90 Bend? Reducing the size of the Final 90 Bend? Tilted Solenoid Pairs: all harmonics except dipole integrate to zero : Lambertson-Coupland terminatio

30 Scanning Requires a combined function field or changing edge angles Development of a CCT For Multipole Fields A key is new mandrel development Minimization of beam Minimization of beam distortion at the patient distortion at the patient A NbTi model - CCT1

31 Direction 2: Curved Helical Quadrupole Focusing Channels or FFAGs with a «twist»: Motivation (fast depth scanning) D. Trbojevic Traditional NS-FFAG: Many small high field, high gradient magnets Desire for fast depth scanning However rapid field changes are challenging for superconducting magnets Superconducting large momentum acceptance gantries (ala NS-FFAG) might enable very fast scanning Curved Helical Quadrupole Focusing Channel Field model developed. Concept of a proton gantry using HFQC is being developed. Optics and tracking studies are in process. Goal of > DP/P = +/-10%

32 Summary: Superconducting gantry magnets may have promise for ion beam therapy. Larger momentum acceptance. More compact The NEW carbon ion gantry replaces the 135 ton magnets of the Heidelberg gantry with 2 ton small BNL or even smaller LBNL superconducting magnets.

33 FFAG are fixed field, can have continuous beam and no degrader Univ. of Kyoto (Japan)

34 A CW FFAG for 400 MeV C 6+ is in design phase at FNAL (C. Johnstone) 2m 5 meter radius CW C 6+ FFAG Parameter 250 MeV 585 MeV 1000 MeV ca A cb B cc C E cd F D G ce cf cg H ch Avg. Radius m m m ν x /ν y (cell) 0.380/ / /0.242 Field F/D 1.62/-0.14 T 2.06/-0.31T 2.35/-0.42 T Magnet Size F/D 1.17/0.38 m 1.59/0.79 m 1.94/1.14 m 5 meter radius CW 250 and330- MeV dual energy proton FFAG Parameter 30 MeV 151 MeV 330 MeV Avg. Radius m m m ν x /ν y (cell) 0.264/ / /0.441 Field F/D 0.97/0.00 T 1.24/-0.09T 1.51/-0.16 T Magnet Size F/D 1.28/- m 2.4/0.92 m 3.18/2.08 m

35 200 MeV, 2 meter,dielectric Wall linear proton Accelerator 50 Hz time structure suitable for protons and Carbon ions lots of R and D remaining Major Issue: Pulsed beam with shot-to-shot fluctuations leading to dose uncertainty

36 Dielectric Wall Accelerator (DWA) incorporates pulse forming lines into a high gradient cell with an insulating wall 1 meter Switch E-field in gaps only State of the Art Electron Induction Accelerator MV/meter Gradient * Patent Pending Z 0 /2 Z 0 Z 0 Z 0 /2 High gradient insulator Important elements for the DWA High gradient insulators PFL architecture Switches Large size dielectrics with high dielectric constant and high bulk breakdown strength

37 200 MeV 2 meter Dielectric Wall Accelerator In development by LLNL and TomoTherapy DWA can be used in the single (nsec) pulse traveling wave" mode for any charge particle up to 50 Hz b Focus electrode Grid Extraction electrode electrode Gate electrode Source Grid Grid Spark discharge proton source* DWA 100 MV/m Proton beam *patent pending Thin vacuum air window Patient

38 PHASER Pluridirectional High-energy Agile Scanning Electronic Radiotherapy (PHASER) for Cancer and Other Major Illnesses by Very High Energy Electrons (VHEE) SU/School of Medicine/SLAC

39 Physical advantages of VHEE Improved depth dose of very high-energy electrons (VHEE) vs. photons DesRosiers Phys Med Biol 2000 B Loo Stanford Radiation Oncology

40 Example: Head/Neck and Prostate cancer M Bazalova et al. Stanford Radiation Oncology

41 Compact Accelerator structures and High Efficiency klystrons tested in the XTA Ultra-high efficiency capable of supporting the highest gradients or extremely high output RF power independently fed to every cell. High-efficiency. >100 MeV/m linac design (shunt impedance >150 MΩ/m) S Tantawi SLAC

42 Novel VHEE intensity modulation Unique 100 MeV compact electron beamline optics design to accelerate & project electron image from source to patient 20x20 cm 2x2 mm C Limborg SLAC

43 Developments in CANADA

44 Cyclotrons in Canada Today Canada has a growing cyclotron infrastructure (enabling PET and soon, SPECT too!) Disease focus: Oncology, Neurology and Cardiology 2 2 Long history starting from TRIUMF Laboratory

45 Accelerators at TRIUMF ISAC (RIB linac) 2 x TR30, CP42, TR13 H - cyclotrons ARIEL (50 MeV electron linac) 500MeV H - cyclotron

46 Commercial Isotope Production CP42 TR30 (2 machines) 15% of Canada s isotopes are produced at TRIUMF Using TRIUMF-designed accelerators, support team 2.5 million patient doses per year, shipped to >40 countries Integrated into commercial supply 35 year partnership

47 Canada s Role in the Recent (Global) Isotope Crisis Medical Isotopes and CANADA Global demand for 99 Mo/ 99m Tc ~ 40 million doses/yr 76,000 scans/day (>1 scan/second) 30-40% of global 99 Mo obtained from NRU in Canada Overall, 5 gov t owned reactors supply >95% of global demand Future demands to increase Recent NRU shutdown: widespread shortages, cost/mci escalating Adding suppliers faces technical and regulatory challenges

48 The MAPLES MAPLE: Multipurpose Applied Physics Lattice Experiment Two identical reactors Purpose: to succeed NRX (1992) and NRU (2016?) Construction started 1997, completed 2000 Dedicated isotope production ( 99 Mo, 60 Co, 133 Xe, 131 I, 125 I) Capable of producing 200% of global 99 Mo/ 99m Tc demand Issues (there are many)*: sticky shut-off safety system positive co-efficient of reactivity use of HEU operating license until 10/31/2011 project terminated 5/16/2008

49 Direct Production of 99m Tc 6 year, $13M effort, TRIUMF-led, 4 institution effort Project Goals: i) Demonstrate routine, reliable, commercial-scale production of 99m Tc via 100 Mo(p,2n); multiple cyclotrons; ii) Obtain regulatory, full-market approval; iii) Commercialize:

50 Decentralized 99m Tc Production NRCan-funded ITAP* 4 years in (ending Canada 2016), $25M, 3 proponents TRIUMF consortium, ERC consortium, CLS/PIPE effort ( 100 Mo(γ,n) 99 Mo) Future cyclotron- 99m Tc sites 2 2 * cont. of NRCan-funded NISP 2 years (ending 2012), $35M

51 Previous Success PET trace: 130 µa, 16 MeV on target for 360 min Demonstrated yields of ~4.7 Ci TR19: 300µA, 18 MeV on target Demonstrated yields of ~9.4 Ci 99m Tc (200 µa, 360 min) 51

52 Direct Production of 99m Tc Progress: 450µA, 24 MeV on target, 360 min, ~32-34Ci 99m Tc Targets for 16, 19, 24 MeV demonstrated Full analysis underway, regulatory submission imminent 52

53 The Major Issue in USA: Compartmentalization Advancing accelerator based research for medicine will require an unprecedented level of cooperation among all stakeholders government agencies, health care providers, laboratories and industry. Legal restrictions, aversion to risk and intellectual property issues on all sides currently hamper successful cooperation between and among these potential partners. Office of High Energy Physics Accelerator R&D Task Force Report, May 2012

54 What Does Exist? Various facilities do exist that are or can be used to support medical applications of accelerators: Various existing facilities could be used to support the radiobiology needed for necessary understanding of proton and ion beam therapy. New accelerator-based technologies are being developed: Compact gantries Superconductivity gantry magnets and cyclotrons Non-traditional lattices -- FFAGs Dielectric wall accelerator Laser acceleration

55 Accelerator Stewardship Congress has mandated accelerator stewardship, facilitating the transfer of accelerator technology out of the national labs and into the business community Various national labs are developing and testing new partnership models in an effort to create unprecedented levels of cooperation

56 The Bright Spot NIH P20 grant (Exploratory Grants) PAR Planning for a National Center for Particle Beam Radiation Therapy Research Awardees (2?) should be announced soon Up to $500,000/yr ea. for two years Hopefully this will evolve into a series of grants, prompting new technological innovation, leading to an ion therapy facility in the US