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
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
Acknowledgments
Thomas Kroc (Fermilab)
David Robin (Berkeley Lab)
Sami Tantawi (SLAC)
Dejan Trbojevic (BNL)
George Coutrakon (NIU)
Paul Schaefer (TRIUMF)
Charged Particle Accelerators for Radiation Therapy
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Charged Particles of interest for therapy: Protons and other
light ions (He2+, C6+, O8+ )  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.
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
Range (cm)
Proton Energy vs Range in Tissue
40
35
30
25
20
15
10
5
0
Series1
0
100
200
Energy (MeV)
300
Light ions ( He, C, O) have a larger biological
Bragg peak and higher peak to entrance ratio
Light ions scatter less in tissue ;
sharper dose fall off on lateral edge of
tumor
Are Carbon ions better than protons?
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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.
Accelerator requirements for cancer therapy
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Energy range; 70-230 MeV P+, 100 - 430 MeV/amu C6+
Dose rate: 1 to 2 Gray per minute per liter of tissue
Rule of thumb: 109 P/cm2/Gray for 5 to 10 cm SOBP
20 cm x 20 cm field size and 40% beam usage, need
1012 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 ?
HISTORY of LABORATORY ACCELERATOR-BASED
MEDICAL RESEARCH and THERAPY (USA)
Laboratory Type of treatment
Years
operational
# of
patients
treated
> 3000 very little 'research' after mid-80's
FNAL
Neutron Therapy
1976 - 2013
LANL
Negative pion therapy
1974 - 1981
228
Berkely
Proton therapy
1954 - 1957
30
Berkeley
184" Cyclotron - p & He
? - 1974
Berkeley
Bevalac - ions
1972 - 1993
433
1961 - 2002
>9000
Harvard
Cyclotron Lab Proton therapy
>1000
10 Facilities in operation in USA in 2011
6 more (not shown) since then from 2012-2014
Central Dupage Hospital
MPRI
MGH - Boston
Univ. of Pennsylvania
Hampton Univ.
Loma Linda Univ.
Medical Center
Barnes Hospital
Oklahoma City
MD Anderson
Scale Legend
0
200
Univ. of Florida
100 18M
400
recently operational
Existing Site before 2010
HOSPITAL-BASED PARTICLE BEAM CANCER
THERAPY FACILITIES (USA)
S/C/SC*
START
BEAM
DIRECTIONS
PARTICLE
MAX.
ENERGY
(MeV)
USA, CA. J. Slater PTC, Loma Linda
p
S 250
3 gantries,
1 horiz.
USA, CA. UCSF, San Francisco
p
C 60
1 horiz.
COUNTRY
WHO, WHERE
MGH Francis H. Burr PTC,
USA, MA.
Boston
p
C 235
TOTAL
PATIENTS
TREATED
DATE OF
TOTAL
1990
17829
13-Dec
1994
1729
14-Dec
OF
TREATMENT
2
gantries***,
2001
1 horiz.
2
gantries***, 2004-2014
1 horiz.
3
gantries***,
2006
1 horiz.
7641
14-Sep
2200
14-Dec Closed
4746
13-Dec
USA, IN.
IU Health PTC, Bloomington
p
C 200
USA, TX.
MD Anderson Cancer
Center, Houston
p
S 250
p
C 230
3 gantries,
1 horiz.
2006
5085
13-Dec
C 230
1 gantry, 1
horiz, 2
horiz/60
deg.
2009
1364
13-Dec
USA, FL. UFPTI, Jacksonville
USA, OK. ProCure PTC, Oklahoma City
p
HOSPITAL-BASED PARTICLE BEAM CANCER
THERAPY FACILITIES (USA), cont’d
USA, PA.
Roberts PTC , UPenn,
Philadelphia
p
C 230
4 gantries,
1 horiz.
2010
2522
14-Dec
2010
1329
13-Dec
USA, IL.
CDH Proton Center, Warrenville
p
C 230
1 gantry, 1
horiz, 2
horiz/60
deg.
USA, VA.
HUPTI, Hampton
p
C 230
4 gantries,
1 horiz.
2010
1200
14-Dec
USA, NY.
ProCure Proton Therapy Center,
New Jersey
p
C 230
4 gantries
2012
1168
14-Dec
USA, WA.
SCCA ProCure Proton Therapy
Center, Seattle
p
C 230
4 gantries
2013
86
13-Dec
USA, MO.
S. Lee Kling PTC, Barnes Jewish
Hospital, St. Louis
p
SC 250
1 gantry
2013
93
14-Oct
USA, TN.
Provision Center for Proton
Therapy, Knoxville
p
C 230
3 gantries
2014
100
14-Aug
USA, CA.
Scripps Proton Therapy Center,
San Diego
p
C 250
3 gantries,
2 horiz.
2014
220
14-Dec
USA, LA.
Willis Knighton Proton Therapy
Cancer Center, Shreveport
p
C 230
1 gantry
2014
28
14-Dec
The accelerator foot prints are small, but not
small or light enough to mount on a gantry or
fit in pre-existing treatment room
LLUMC Proton Synchrotron
Synchrotrons
Particle Therapy Vendor List
(Mevion below and Varian 250 MeV cyclotron are
Superconducting machines)
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Mitsubishi 250 MeV Synchrotron
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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
Heidelberg Heavy Ion Facility and
Accelerator (offered by Siemens)
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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
230 MeV Proton Cyclotron offered
by IBA of Belgium
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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
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
1st patient treatments expected by end of 2013
ProTom 330 MeV proton
synchrotron
Varian SC 250 MeV Proton Cyclotron
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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
Hitachi Proton Therapy Synchrotron
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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
Vendor Activity Score
IBA/
Hita- Mitsu Sumi- Varian
Procure chi
-bishi tomo
Siemens
Complete 10-12
and Built
2
2
1
1
0
Complete
In Prog.
Partial
Systems
?
2
?
1
2
2
2
2
3
2
1
1
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)
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!!
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
 High
Field Angle (90°)
Large
Bending
 Large
Bending
(90°)
Large
Aperture
(20Angle
x 20 cm)
 Large Aperture
x 20 cm)
Combined
Function(20
Fields
 Combined
Fields
(large
SAD andFunction
small distortion)
(large SAD
and
small distortion)
• Rotatable
(up to
360°)
• Rotatable
(up (up
to 360°)
• Fast
Ramp Rates
to 1 T/s)
• Fast Ramp Rates (up to 1 T/s)
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• Large Aperture Curved
Canted Cosine Theta
(CCT) Magnet
• Curved Helical
Quadrupole Focusing
Channels
Start with Pavlovic Type Gantry Design
Direction1:
1:
Direction
Reducingthe
thesize
sizeof
ofthe
theFinal
Final90°
90°Bend?
Bend? Tilted Solenoid Pairs: all harmonics except dipole
Reducing
integrate to zero : Lambertson-Coupland terminatio
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
Direction 2: Curved Helical Quadrupole Focusing Channels or
FFAGs with a «twist»: Motivation (fast depth scanning)
Traditional NS-FFAG: Many small high
field, high gradient magnets
D. Trbojevic
• 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%
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.
FFAG are fixed field, can have
continuous beam and no degrader
Univ. of Kyoto (Japan)
A CW FFAG for 400 MeV C6+ is in design phase at FNAL
(C. Johnstone)
5 meter radius CW C6+ FFAG
2m
Parameter
5.0
4.5
4.0
3.5
3.0
2.5
cA
A
cB
C
cD
D
G
cE cF H
cG cH
0.5 1.0 1.5 2.0 2.5 3.0 3.5
F
585 MeV
1000 MeV
Avg. Radius
3.419 m
4.307 m
5.030 m
νx /νy (cell)
0.380/0.237
0.400/0.149
0.383/0.242
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
cC
B
E
250 MeV
5 meter radius CW 250 and330MeV dual energy proton FFAG
Parameter
30 MeV
151 MeV
330 MeV
Avg. Radius
1.923 m
4.064 m
5.405 m
νx /νy (cell)
0.264/0.366
0.358/0.405
0.-/0.441
Field F/D
0.97/0.00 T
1.24/-0.09T
1.51/-0.16 T
1.28/- m
2.4/0.92 m
3.18/2.08 m
Magnet Size F/D
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
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
Important elements for the DWA
Z0/2
Z0/2
* Patent Pending
Z0
Z0
State of the Art Electron
Induction Accelerator
≈ 0.3 - 0.5 MV/meter Gradient
High
gradient
insulator
•
•
•
•
High gradient insulators
PFL architecture
Switches
Large size dielectrics with
high dielectric constant and
high bulk breakdown strength
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
Patient
DWA 100
100 MV/m
MV/m
DWA
Source
Grid
Grid
Spark discharge
proton source*
Proton beam
*patent pending
Thin vacuum
air window
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
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
Example: Head/Neck and Prostate
cancer
M Bazalova et al. – Stanford Radiation Oncology
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
Novel VHEE intensity modulation
Unique 100 MeV compact electron beamline optics
design to accelerate & project electron “image” from
20x20 cm
source to patient
2x2 mm
C Limborg – SLAC
Developments
in
CANADA
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
Accelerators at TRIUMF
ISAC (RIB linac)
2 x TR30, CP42, TR13
H- cyclotrons
ARIEL
(50 MeV
electron linac)
500MeV
H- cyclotron
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
Canada’s Role in the Recent
Medical(Global)
Isotopes
and
CANADA
Isotope
Crisis
Global demand for 99Mo/99mTc ~ 40 million doses/yr
76,000 scans/day (>1 scan/second)
30-40% of global 99Mo 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
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 (99Mo, 60Co, 133Xe, 131I, 125I)
• Capable of producing 200% of global 99Mo/99mTc 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
Direct Production of 99mTc
• 6 year, $13M effort, TRIUMF-led, 4 institution effort
• Project Goals:
i) Demonstrate routine, reliable, commercial-scale
production of 99mTc via 100Mo(p,2n); multiple
cyclotrons;
ii) Obtain regulatory, full-market approval;
iii) Commercialize:
Decentralized 99mTc Production
NRCan-funded ITAP* – 4 years
2016), $25M, 3 proponents
in (ending
Canada
 TRIUMF consortium,
 ERC consortium,
 CLS/PIPE effort (100Mo(γ,n)99Mo)
 Future cyclotron-99mTc sites
2
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2
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* cont. of NRCan-funded NISP – 2 years (ending 2012), $35M

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 99mTc (200 µA, 360 min)
51
Direct Production of 99mTc
• Progress: 450µA, 24 MeV on target, 360 min, ~32-34Ci
99mTc
– Targets for 16, 19, 24 MeV demonstrated
– Full analysis underway, regulatory submission imminent
52
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
What Does Exist?

Various facilities do exist that are or can be used
to support medical applications of accelerators:

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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

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
The Bright Spot

NIH P20 grant (Exploratory Grants)
PAR-13-371 “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