Http:// Ken.Peach@adams-institute.ac.uk Charged Particle Therapy: Physicists meet Physicians Ken...

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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

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

Cancer

A Challenge for today and tomorrow

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

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

Cancer is a horrid disease

…but there is hope

15 months after RT

malignant melanoma

C+, Chiba (Professor Tsujii, Japan)

Chemotherapy is very aggressive!

Curing cancer with accelerators

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

X-ray therapy began within months of Roentgen’s discovery

Curing Cancer with X-rays

Intensity Modulated Radiation Therapy (IMRT)

Charged Particle Therapy (CPT)

Proton and light ion therapy

Plateau

The Bragg Peak

Can we do better?

Proton

The Bragg Peak

Is it better?

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

Intracranial Tumour

17 month old childFrom Alex Elliott

Proton Therapy in Physics Labs

Catania GSI

Uppsala

Hahn-Meitner Institute

Wasaka Energy Research Institute

Early facilities

CPT Facilities: Present Situation

Proton Therapy in hospital

Clatterbridge

Loma Linda

Massachusetts

CPT Facilities: Development Plans

A Proton Therapy Centre

A rotating gantry

Japan: Tsukuba UniversityJapan: Tsukuba UniversityNew Proton Medical Research Centre, 2001New Proton Medical Research Centre, 2001

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

Prostate Cancer Results

Loma Linde

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

BBC 7th November 2008

Can we do even better?

Carbon

Civil Engineering and Layout - HIT

Hadron Therapy in Chiba (Japan)

Borrowed from Rob Edgecock

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

Spot Scanning

Target

Magnetic scanner

‘Range shifter’ protect

Patient

Proton pencil beam

Pedroni et al, Med Phys. 22:37-53, 1995

CPT in the UK

Why is proton therapy not more widely available?

• 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

CONFORM

An example: Which is better – p, C, ??

Damage to healthy tissueDamage to the tumour

Once the cancer cell is killed by a single ion, increasing Z just damages healthy tissue

Optimum

The state of play

“reported studies are heterogeneous in design and do not allow for strict conclusions”

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

Some more views

Prostate Cancer Results

Loma Linda

Are these equivalent samples?

Hot from the press

6.4%12.8%

CPT involves discomfort

South Africa (eye)

Chiba, Japan (Lung)

(medullablastoma)

From Proton & CP Radiotherapy, ed Delaney & Kooy

… and more illustrations

From Proton & CP Radiotherapy, ed Delaney & Kooy Indiana (eye)

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

PAMELA

Particle Accelerator for MEdicaL Application

Clinical Requirements

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.

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) …

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 …

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

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

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

PAMELA

Particle Accelerator for MEdical Applications

Fixed Field Alternating Gradient Accelerator

Protons or carbon ions

Part of the CONFORM Project

Design PAMELA

Oxford-Imperial-RAL-Daresbury

A possible layout

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

“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

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

Backup slides

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

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]

Http:// Ken.Peach@adams-institute.ac.uk Charged Particle Therapy: Physicists meet Physicians Ken...

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