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![Page 1: Http:// Ken.Peach@adams-institute.ac.uk Charged Particle Therapy: Physicists meet Physicians Ken Peach John Adams Institute for.](https://reader036.fdocuments.us/reader036/viewer/2022062421/56649e2a5503460f94b18536/html5/thumbnails/1.jpg)
http://www.adams-institute.ac.uk [email protected]
Charged Particle Therapy: Physicists meet Physicians
Ken PeachJohn Adams Institute for Accelerator Science
University of Oxford and Royal Holloway University of London
&Particle Therapy Cancer Research Institute
(part of the James Martin 21st Century School, Oxford)
Imperial1st April 2009
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 2
Outline
• Cancer– A challenge for today & tomorrow
• Curing Cancer (with accelerators)
– Charged Particle Therapy (CPT)• (proton and light-ion cancer treatment)
PAMELA
• Summary
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 4
Incidence of Cancer in the UK
• 12.5% probability, all types (except skin cancer) by 65– Rises to more than 1/3rd for whole-life– Around half are associated with specific risks– Statistically, some will be close to sensitive tissue
• and difficult to treat surgically or chemically
Source: Cancer Research UK
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 5
An important statisticAn important statistic
“ Radiotherapy remains a mainstay in the treatment of cancer. Comparison of the contribution towards cure by the major cancer treatment modalities shows that of those cured, 49% are cured by surgery, 40% by radiotherapy and 11% by chemotherapy”.
RCR document BFCO(03)3, (2003).
Chemotherapy provides by far the smallest contribution towards cancer cure yet is much more expensive than radiotherapy and generates a disproportionately large research and media interest.
Roger Dale, Hammersmith Hospital and Imperial College
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 6
Cancer is a horrid disease
Liver
…but there is hope
15 months after RT
malignant melanoma
C+, Chiba (Professor Tsujii, Japan)
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 7
Chemotherapy is very aggressive!
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 9
Development of Cancer RadiotherapyDevelopment of Cancer Radiotherapy
• 1895 : Rontgen’s X-rays1895 : Rontgen’s X-rays• 1898 - Marie Curie’s Radium1898 - Marie Curie’s Radium• Radium and x-ray machines Radium and x-ray machines
– used to treat cancerused to treat cancer
• Most current radiotherapy Most current radiotherapy – High energy X-ray beams High energy X-ray beams
• linear accelerators or ‘linacs’linear accelerators or ‘linacs’
• X-rays pass through bodyX-rays pass through body © Varian
© Varian
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 10
X-ray therapy began within months of Roentgen’s discovery
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 11
Curing Cancer with X-rays
Dose
Linac
Linac
Linac
Linac
Linac
Linac
Linac
Linac
Linac
Linac
Linac
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 12
Intensity Modulated Radiation Therapy (IMRT)
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http://www.adams-institute.ac.uk [email protected]
Charged Particle Therapy (CPT)
Proton and light ion therapy
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 14
Bragg
peak
Plateau
The Bragg Peak
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 15
Can we do better?
Dose
Proton
Proto
n
The Bragg Peak
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 16
Is it better?
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 17
100
60
10
With X-raysWith Protons
Medulloblastoma in a child
“When proton therapy facilities become available it will become malpractice not to
use them for children [with cancer].”Herman Suit, M.D., D.Phil., Chair, Radiation Medicine, Massachusetts
General Hospital
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 18
Intracranial Tumour
17 month old childFrom Alex Elliott
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 19
Proton Therapy in Physics Labs
Catania GSI
Uppsala
Hahn-Meitner Institute
PSI
Wasaka Energy Research Institute
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 20
Early facilities
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 21
CPT Facilities: Present Situation
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 22
Proton Therapy in hospital
Clatterbridge
Loma Linda
Massachusetts
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 23
CPT Facilities: Development Plans
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 24
A Proton Therapy Centre
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 25
A rotating gantry
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 26
Japan: Tsukuba UniversityJapan: Tsukuba UniversityNew Proton Medical Research Centre, 2001New Proton Medical Research Centre, 2001
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 27
The Clatterbridge Centre for Oncology
• Established 1989 – First hospital based
proton therapy – >1400 patients with
ocular melanoma– First example of 3D
computer treatment planning in UK;
• eye gaze direction used to obtain best approach angle to eye.
• Unsung success story of British Oncology!
After Bleddyn Jones
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 28
Prostate Cancer Results
Loma Linde
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 29
Clinical uses
• Mostly eye cancers• Relatively rare primary cancers
– skull base or spine• difficult to cure with x-rays
• Far fewer for common cancers – Lung– Oesophagus– Breast– Kidney– Liver– Pancreas– Prostate
From Alex Elliott
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BBC 7th November 2008
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 31
Can we do even better?
Dose
Carbon
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 32
Civil Engineering and Layout - HIT
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 33
Hadron Therapy in Chiba (Japan)
Borrowed from Rob Edgecock
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 34
Cancer of the Kidney Stage I: TIa N0 M0 80GyE / 16fr. /4wks
Cancer of the Kidney Stage I: TIa N0 M0 80GyE / 16fr. /4wks
治療前
1 year1 year2 years2 years
3 years3 years5 years5 years
Does it work?
From Japan
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 35
Spot Scanning
Target
Magnetic scanner
‘Range shifter’ protect
Patient
Proton pencil beam
Pedroni et al, Med Phys. 22:37-53, 1995
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http://www.adams-institute.ac.uk [email protected]
CPT in the UK
Why is proton therapy not more widely available?
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 37
• CPT has moved from laboratory to hospital– Where it belongs
• But there is still much to do1. Improved accelerator technology
• Improved patient experience, better control 2. Improved beam delivery & instrumentation
• Better control, reduced errors, lower dose to healthy tissue3. Improved understanding of the evidence
• Better treatment planning, domains of applicability4. Improved treatment regimes
• Better ways of delivering the lethal dose to the tumour5. Improved understanding of mechanisms
• Better treatment planning, more effective outcomes
• Improve - patient experience - increase effectiveness- decrease cost
CPT: What remains to be done?
CONFORM/PAMELA
FP7/ULICE
FP7/ENVISION
FP7/ENVISION
CONFORM
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 38
An example: Which is better – p, C, ??
Z
Damage to healthy tissueDamage to the tumour
1
Once the cancer cell is killed by a single ion, increasing Z just damages healthy tissue
Optimum
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 39
The state of play
“reported studies are heterogeneous in design and do not allow for strict conclusions”
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 40
Conclusion (from Olsen et al)
“ The evidence on clinical efficacy of proton therapy relies to a large extent on non-controlled studies, and thus is associated with low level of evidence according to standard heath technology assessment and evidence based medicine criteria
”
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 41
Some more views
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 42
Prostate Cancer Results
Loma Linda
Are these equivalent samples?
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 43
Hot from the press
6.4%12.8%
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 44
CPT involves discomfort
South Africa (eye)
Chiba, Japan (Lung)
C-ion
(medullablastoma)
From Proton & CP Radiotherapy, ed Delaney & Kooy
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 45
… and more illustrations
From Proton & CP Radiotherapy, ed Delaney & Kooy Indiana (eye)
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 46
The requirements
• There are obvious potential benefits from proton/light ion therapy– Need to maximise the benefits
• Requirements– Rapid variable energy extraction– Rapid variable transverse spot scanning– Variable ion species– Accurate dose measurements
• Flux control
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http://www.adams-institute.ac.uk [email protected]
PAMELA
Particle Accelerator for MEdicaL Application
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Clinical Requirements
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 49
PAMELA Objectives
• Produce the conceptual design for a combined proton/carbon/light ion cancer therapy facility– 250 MeV protons, 400 MeV/u Carbon
• Preliminary performance parameters– >100 Hz cycle rate and one turn ejection– Dose rate of 2 to 10 Gy/minute.
• (1Gy ~ 2 x 1010 protons)
– Voxel size from 4x4x4 mm3 to 10x10x10 mm3
– Up to 100 pulses/voxel• With a typical tumour volume of 250 cm3 & voxel-
volume 0.064 cm3 (4x4x4), there are 4,000 elements, which with 10 to 100 pulses for each voxel needs 40k to 400k pulses in around 300 seconds, or a cycle rate of 133 Hz to 1.3 kHz.
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 50
Classical Accelerator Types
Type Magnetic Field
RF Radius
Betatron Variable ✘ Fixed
Cyclotron Fixed Variable
Synchrotron Variable Fixed
FFAG Fixed ~Fixed
Linear accelerators
(Linacs) ✘ ∞+ assorted others – electrostatic, RFQs etc …
+ new ideas (laser-plasma for example) …
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 51
Accelerator Technology?
• 4 possible technologies– Cyclotrons
• Fixed energy extraction, difficult for Carbon at full energy (equivalent to 1.2 GeV/c protons)
– Synchrotrons• Flexible, but difficult to meet the pulse
requirements; slow extraction difficult; normal conducting machine (stability?)
– (ns) FFAG• Flexible, rapid cycling (fixed field), variable
energy … but … unproven technology
– Laser-Plasma Ion accelerators• Far in the future …
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 52
Fixed Field Alternating Gradient accelerators
• Fixed-Field (like a cyclotron)
– Rapid acceleration possible– Rapid cycling possible
• Alternating Gradient (like a synchrotron)
– Focussing!!!!• Small(er) magnets/beam pipe/vacuum system
• … and large acceptance
• The best of both worlds!– So why is the world not full of FFAGs?
• See Jaroslaw’ talk 2 weeks ago …
Type Magnetic Field RF Radius
FFAG Fixed ~Fixed
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 53
Challenges
• The non-relativistic, non-scaling Fixed-Field Alternating Gradient Accelerator (nrns-FFAG) is a new type of accelerator– Dense lattice– Challenging magnets, RF, injections
and extraction– Resonance crossing– Stability
• EMMA will demonstrate the ns-FFAG• PAMELA will demonstrate the nrns-FFAG
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 54
Status
• Studies underway using a test lattice– Magnets – probably combined function
superconducting magnets– RF – a number of schemes are being
considered– Injection and extraction – will constrain the
lattice parameters
• Aim– Lattice cell defined at end of 2008– Work through the design in 2009– Incorporate the lessons from EMMA– Produce a conceptual design in 2010
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 55
PAMELA
Particle Accelerator for MEdical Applications
Fixed Field Alternating Gradient Accelerator
Protons or carbon ions
Protons or carbon ions
Part of the CONFORM Project
Design PAMELA
Oxford-Imperial-RAL-Daresbury
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 56
A possible layout
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 57
Status
• Ion Source and pre-accelerator– Ideas for the design
• (build from scratch or use an existing cyclotron)
• Accelerator– Lattice design under review
• Magnets look feasible• RF being studied
• Extraction (& injection)– Ideas being studied
• Beam transport– FFAG-like beam transport looks promising
• Gantry– Needs and FFAG-like gantry
• Instrumentation and Dosimetry– R&D required
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http://www.adams-institute.ac.uk [email protected]
“Medical advances may seem like wizardry. But pull back the curtain, and sitting at the lever is a high-energy physicist, a combinational chemist or an engineer. Magnetic resonance imaging is an excellent example. Perhaps the last century's greatest advance in diagnosis, MRI is the product of atomic, nuclear and high-energy physics, quantum chemistry, computer science, cryogenics, solid state physics and applied medicine.”
Harold Varmus, Nobel Laureate in Medicine, Washington Post, 2000
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 59
Summary
• Cancer is a dreadful disease– But there is hope
• Charged Particle Therapy is effective– But can be improved
• Existing accelerator technology works– But with limitations
• Particle physics ideas for the neutrino factory– May provide a better solution
• Let us hope that we don’t need it ourselves– But be aware that there is a 1:3 chance that we will
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 61
Cost of CPT
• (numbers approximate)– Capital cost (4 rooms)
£100M– Running costs per annum £15M– Capital charges (20 years) £100M– Total cost £500M– Cost/year £25M
• Patient throughput– 30min/patient, 12 hr/day, 5 days/week
» 25000 patient sessions/year
– 35 fractions/patient» 700 patients/year» £36,000 per patient
20 fraction/patient & 3 patients/hour
1800 patients/year
£14,000 per patient- reduced cost of other care
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Ken Peach John Adams Institute From Neutrino Oscillations to Curing Cancer 1st April 2009 62
How many centres?
• 2005: 289k new cases– 1390 under 15– Estimates suggest that 1
proton centre is required per 10 million population
– & 1/3rd that number of carbon centres
– UK population 60M– Implies ~8 proton centres
• [1 each in Scotland, Wales and N.I, SW and N of England, 3 in Midlands and SE]
– & 2 carbon centres– Capacity for ~ 10,000
patients/year [£300M]