Institute of Physics and Engineering in Medicine
Spotlight on
05
Proton and Ion Therapy
Perspectives on:
physics and engineering in medicine and biology
Spotlight5.indd 1
Institute of Physics
and Engineering in Medicine
29/01/2008 21:07:36
Proton and Ion Therapies provide cancer
treatment with minimal side-effects
Picture provided by Clatterbridge Centre for Oncology
Picture provided by Clatterbridge Centre for Oncology
The upper image shows a modulator
wheel. Each vane is made from
Perspex of a different thickness.
Placing the wheel between patient
and beam, and rotating it during the
treatment, allows a single-energy
beam to reach every depth within
a tumour. The width and height of
a tumour can be covered either by
scanning across it, or by directing a
widened beam at a brass collimator
- like the one shown in the bottom
image here - that only allows the
beam to pass through the tumourshaped hole in its centre.
Many forms of cancer can be treated with
conventional radiotherapy in which beams
of X-rays or gamma rays are directed at
tumours. The energy deposited by the
radiation kills some of the cancer cells, but
also damages the healthy tissues the beam
passes through on its journey to the tumour
and further on through the body. This
results in side effects such as diarrhoea and
abnormal organ functioning, and the risk of
inducing future cancers. The latest forms of
‘particle’ radiotherapy - proton therapy and
ion therapy - promise to dramatically reduce
the amount of collateral tissue damage, and
hence many side effects, as most of their
energy can be deposited within the cancer
rather than in healthy tissues.
Particle therapies use high-energy beams
of protons (positively charged particles) or
positive ions (in this case, atoms that have
had all of their electrons removed). While
able to treat a wide range of cancers, they
are particularly suitable for treating small
tumours that have been detected prior to
the cancer spreading, and provide a viable
alternative to risky surgical tumour removal
from deep organs. Particle therapies also
enable treatment of tumours that are
inoperable and unsuitable for conventional
radiotherapy because they are close
to critical organs such as the spine or
brain. In addition proton therapy has had
considerable success treating small tumours
in the eye.
As well as reducing damage to healthy
tissue, particle therapies can potentially be
delivered in far fewer treatment sessions
than established radiotherapy. For example
in Japan the 30 or more sessions of
conventional radiotherapy that small lung
and liver cancers require has been replaced
by a single particle beam treatment.
05
How Proton and Ion Therapy
works
Particle radiation kills cancer cells by
altering their DNA. Changes such as DNA
strand breakage are either the result of a
direct hit from the radiation, or more usually
occur after the water surrounding the DNA
has been ionised by the radiation. Water
molecules consist of two hydrogen atoms
and an oxygen atom, but ionised water
molecules can break up into hydrogen
nuclei and hydroxyl radicals comprised of
one oxygen atom and a single hydrogen
atom. These hydroxyl radicals can
transform back into water molecules by
stealing hydrogen atoms out of a nearby
DNA strand which, if a sufficient number
of breaks occur close to each other, is
irreparably damaged as a result.
As charged particles pass through tissue
they slow down and the slower they get
the more ionisation they produce. So the
beams of particles used in these therapies
are made to stop within, and around the
boundaries of, a cancer whose position and
shape has been accurately determined via
a CT or MRI scan. The particles therefore
create by far the most ionisation (and direct
DNA hits) in the cancer cells, rather than in
the healthy cells passed en route.
Higher energy charged particle beams can
penetrate further into tissue than beams of
lower energies, but some therapy beams
have a fixed energy. So they can reach the
required depths within the tumour, these
beams are passed through a succession
of different thickness materials before
entering the patient. The extra distance
travelled in each material reduces the
beam penetration by a different amount,
allowing a range of depths to be reached.
For convenience the different thickness
materials can be arranged as vanes on a
‘modulator wheel’ (see image top left).
Particle beams must also cover the
entire width and height of tumours. This
is achieved either by scanning the beam
across the tumour, or by widening the beam
and using it in conjunction with a metal
plate known as a collimator (see image
bottom left). This is thick enough to stop the
particles completely, and is custom-made
so that the hole cut out of it matches the
shape of the tumour. Placing the collimator
immediately in front of the patient ensures
that the only part of a widened beam that
reaches the patient corresponds to the
shape of their tumour.
Proton and Ion Therapy
Spotlight5.indd 2
29/01/2008 21:07:39
Picture provided by Clatterbridge Centre for Oncology
The Clatterbridge Centre
for Oncology in the Wirral
has been successfully
treating eye tumours
since 1989, and was the
world’s first hospital based
proton therapy centre.
In this picture a patient
awaits treatment in a chair
which can be positioned
with enough precision
to enable complete and
consistent coverage of
their tumour by the fixed
beam. The UK’s National
Physical Laboratory offers
the ‘standard’ calibration of
dose measuring equipment
used in this system, and in
several other systems in
mainland Europe.
In the future, different particles could be
used to treat different types of cancer. For
example carbon ions should prove better at
killing large tumours with a reduced central
blood supply than X-rays or protons, which
rely on oxygen carried by the blood to
enhance their effectiveness.
Producing and guiding the
particle beams
The diagram on the back page shows the
main stages of particle therapy delivery. First
the protons or ions are accelerated up
to the high energy required to travel into the
body in either a cyclotron or synchrotron
particle accelerator. (The left-hand cover
image shows the superconducting cyclotron
used to deliver proton radiation therapy
at the Paul Scherrer Institute (PSI) in
Switzerland.)
Magnets are then used to bend the beam,
guiding it from the accelerator into the
treatment room. Additional magnets - in
some cases mounted on metal gantries that
can move 360º around the patient - then
steer the beam into the tumour. (The righthand cover image shows the gantries and
treatment couch at the PSI.) Wire chambers
provide a check on beam position by
measuring where the charged particles pass
through them, while ionisation chambers
check the strength of the beam by recording
the amount of ionisation it produces in the air
between the chamber plates.
Advantages
The major potential advantage of proton and
ion therapies is that they substantially reduce
damage to healthy tissues and organs. This
not only lessens the likelihood of inducing
new cancers, but also prevents effects such
as weakening of bones that can lead to
osteoporosis, and allows survival of more
Spotlight5.indd 3
bone marrow so that patients can tolerate
chemotherapy treatment better. It can also
provide an alternative for patients unlikely
to survive surgical tumour removal, or
who have diseased organs - which might
deteriorate further if irradiated - adjacent to
cancers.
With fewer side effects that require additional
treatment, it should be possible to treat
patients more quickly, reducing the overall
cost of treating cancer as well as improving
the patient experience.
Availability in the UK
The numbers of ‘high energy’ particle
treatment centres (with beams with enough
energy to reach any body area) in operation
or being built are rapidly increasing in Japan
(12), the USA (12), Italy (2), Germany (6),
Switzerland (1), Austria (1), Sweden (1)
and France (3). The UK lags behind this
level of implementation with only one ‘low
energy’ centre, the Clatterbridge Centre for
Oncology, which uses proton therapy to treat
eye tumours (see picture above).
Although long term medical and cost
effectiveness is unknown, early results
indicate that particle therapies provide
at least a similar treatment outcome to
conventional radiotherapy, and have fewer
side effects. Experts suggest that if the UK
wishes to form part of the international effort
to evaluate and optimise the procedure,
either one large centre or 3-4 smaller centres
need to be set up. These would be able
to offer treatments as part of randomised
clinical trials, which would compare the new
therapies with standard radiotherapy.
Each treatment centre would need its own
cyclotron or synchrotron. To offset the
initial cost of these accelerators, they could
be used overnight to produce radioactive
isotopes for nuclear medicine treatments and
diagnosis, or to test satellite components by
simulating the effects of cosmic radiation. In
addition, medical physicists and clinicians
need education and training in order to
identify and refer suitable patients abroad
for particle treatments, and potentially to UK
centres in the future.
29/01/2008 21:07:40
05
Institute of Physics and Engineering in Medicine
Perspectives on:
physics and engineering in medicine and biology
Siemens press picture
Synchrotron
(Particles up to
70% of light speed)
Ion Source
Carbon
Scanning System
Online Monitoring
Monitor
System
Scanning
Magnets
Wire
Chambers
Ionization
Chambers
Target
Volume
Example
Depth 5 cm:
Proton 80 MeV
Carbon 145 MeV/u
Depth 25cm:
Proton 195 MeV
Carbon 375 MeV/u
Radiation Control
Cross-section
through the
irradiated tumor
volume. Every
section represents
a different beam
range. The treated
elements are
shown in green.
Relative
Dose
0
Depth
The main stages involved in delivering particle beam radiotherapy. (This system can produce beams of varying energy, so does
not need a modulator.) Worldwide there are five main suppliers of particle therapy equipment: Siemens, IBA, Mitsubishi, Hitachi
and Varian.
Perspectives is a series of publications which highlights new and
emerging areas of research in physics and engineering, and discusses
their application to the solution of problems in medicine and biology.
Acknowledgement
Much of the information in this perspective was kindly provided by
Professor Bleddyn Jones and Dr Stuart Green (Birmingham Cancer
Centre, University Hospital NHS Foundation Trust, Birmingham),
Dr Hugo Palmans (National Physical Laboratory), and Dr Andrzej
Kacperek (Clatterbridge Centre for Oncology NHS Foundation Trust,
Wirral).
Institute of Physics and Engineering in Medicine
Fairmount House
230 Tadcaster Road
York YO24 1ES
United Kingdom
Spotlight5.indd 4
Enquiries:
Tel: +44 (0)1904 610821
Fax: +44 (0)1904 612279
office@ipem.ac.uk
www.ipem.ac.uk
Editor: Dr Sharon Ann Holgate, Design: Louise Southwell, © Institute of Physics
and Engineering in Medicine. Cover photographs PSI, Villigen, Switzerland.
Linear Accelerator
Ion Source
Proton
29/01/2008 21:07:42