Proton therapyat the Paul Scherrer Institute

PSI proton therapy for tumours of the eye (OPTIS). The patient’s head is fi xed using a mask and a bite block. Actual irradiation of the eye tumour lasts less than

one minute. Four separate irradiations have to be carried out on four consecutive days.

33

The aim of the radiotherapy system provided at

the Paul Scherrer Institute (PSI) is to use charged

particles, called protons, to destroy cancerous

tissue. Protons are particularly suited to this task

because they exert their greatest impact deep

within a patient’s body, inside the tumour itself.

Thanks to an irradiation technique that is the only

one of its kind world-wide, the innovative proton

therapy facility at PSI is able to adapt the radia-

tion dose extremely accurately to the shape of a

tumour (which is usually irregular). As a result,

this technique is able to safeguard healthy tissue

better than the conventional modern radiotherapy

techniques.

Tumours of the eye were treated with radiation at

PSI for the fi rst time in 1984. This was the fi rst

installation of this type anywhere in Europe. The

fi rst proton gantry for the irradiation of deep-

seated tumours was taken into service at PSI in

1996, and was also the fi rst in Europe. With the

ongoing development of this innovative irradiation

technique, it shall be possible in future to irradiate

also tumours which move during treatment (e.g.

breast and lung cancer) with a high degree of

precision. PSI is a leader in the technological

development of proton therapy, setting world-wide

trends in radiotherapy for cancerous tumours.

Proton therapyat the Paul Scherrer Institute

OPTIS facility for the irradiation of eye tumours using protons. After the proton beams have been adjusted precisely to the

tumour in the eye, the irradiation is carried out. More than 5000 patients have so far benefi ted from this therapy at PSI.

4 P R O T O N T H E R A P Y AT P S I

Improved radiation therapy

means

• more precise match between

the radiation dose and the

shape of the tumour

• higher radiation dose in the

target volumes (tumour plus

safety zone)

• lower radiation stress for

healthy structures in the

body

• better, more sustainable

odds on recovery

• fewer side effects

• better quality of life

• justifi able treatment costs

This can signifi cantly reduce, or even prevent, short

and long term side effects.

Radiation therapy, or radiotherapy, is a local

method of treatment (like surgery), and it is there-

fore used to fi ght against tumours that are limited

to a specifi c location. It is not interchangeable with

therapies that have to act on the whole body (sys-

temic therapies), such as chemotherapy and immu-

notherapy (especially for the treatment of metas-

tases).

In radiation therapy, the tumour cells are

destroyed by x-ray or gamma radiation (photon

therapy) or by particle radiation (e.g. proton ther-

apy). The aim of each additional stage in the

development of radiotherapy is to destroy the

tumour completely, while being even better at

safeguarding healthy tissue.

Great progress has been made in conventional

radiotherapy during the past 20 years. Neverthe-

less, proton therapy can help to achieve signifi -

cantly better results for certain tumour indications

and tumour localisations. The developments at PSI

also demonstrate that the potential for improve-

ment is still far from exhausted.

How does radiotherapy work?

If a charged particle (e.g. a proton) passes through

a cell, or stops within, the energy it deposits (the

dose) damages the core of that cell. Under certain

circumstances, however, the cell can repair this

damage. The art of radiotherapy is to deliver the

dose in such a way that the tumour cells do not

have any chance to repair themselves, so that they

all die off, without any exception, but that the

healthy cells suffer as little damage as possible,

and are able to recover without any diffi culty.

The radiation dose is a measure of the energy

absorbed in a material, e.g. in tissue. However, the

biological effect of radiation is not just dependent

on how much energy is deposited in the cells, but

also on the way in which it is deposited. The energy

dose is measured in Gray (Gy). A typical therapy

dose used to destroy a tumour would be about 60

to 70 Gy. It is delivered in individual fractional

doses on several consecutive days of radiotherapy

(about 30 to 40 fractional doses in total).

Radiotherapy and its signifi cance

It is anticipated that one in every three people in

Europe will suffer from cancer at some point in

their lives. In Switzerland alone, about 30,000

people discover that they have cancer every year.

Around 70 % of these will require radiotherapy

during their illness. A little more than 45 % of all

the tumours diagnosed today are curable, where

«curable» is taken to mean that the patient lives

without suffering any new outbreak of cancerous

disease for more than fi ve years after treatment.

About 22 % owe their recovery to surgery, about

12 % to radiotherapy, about 6 % to a combination

of both methods and about 5% (metastasised and

non-localised tumours) to other treatments and

combinations, including chemotherapy.

Radiotherapy is therefore an important form

of treatment, and is often the only possibility in

the case of non-operable tumours. In the case of

treatment for primary tumours, the odds are

improving for recovery, and therefore for life

expectancy. It is therefore all the more important

that radiotherapy should be administered as pre-

cisely as possible, and that the healthy areas of

the body should be irradiated as little as possible.

PSI proton therapy for tumours of the eye, using a special

proton beam with a low penetration depth (OPTIS).

These photographs through the pupil show the interior of

the eye; above before proton therapy, below one year

later – the tumour has shrunk.

5P R O T O N T H E R A P Y AT P S I

Proton therapy world-wide and at PSI

Proton therapy is based on experience gathered

over more than 50 years on the biological effect of

proton radiation on diseased and healthy tissue

in the body. A patient was treated with protons for

the fi rst time at the Lawrence Berkeley Laboratory

in California (USA) in 1954, and the fi rst proton

therapy programme in Europe ran in Uppsala

(Sweden) between 1957 and 1976. In 1961, the

Harvard Cyclotron Laboratory and the Massachu-

setts General Hospital in Boston, USA, started a

proton therapy project. Melanoma of the eye was

treated with protons for the fi rst time in Europe in

1984, at the OPTIS facility developed especially for

this purpose at PSI.

The fi rst proton therapy facility to be used at

a hospital went into operation at the Loma Linda

University Medical Center, California, in 1990. Fol-

lowing a development and testing phase of almost

10 years, up to 1500 patients have routinely ben-

efi ted from proton therapy there since 1999. Today

there are more than 35 centers in operation world-

wide, and already more than 80,000 patients have

been treated with Proton therapy, nearly 10 % of

them at PSI.

The technique known as Spot-Scanning, used

to treat deep-seated tumours with protons, was

developed at PSI at the beginning of the 1990s.

This PSI technology is superior to the proton

radiation methods used in other centres, and

provides better protection for healthy tissue. This

extremely precise method has been used to treat

patients with tumours that are particularly hard to

treat at PSI since 1996. As well as PSI, there are

now six other operational proton therapy facilities

in Europe, three of these are only able to treat

tumours of the eye. World-wide, there are more

than 30 proton therapy projects currently under

construction or at a late stage of planning, and

approximately 10 of these are located in Europe.

Today, more than 10,000 patients per year are

treated with protons at about 35 centers world-

wide. Most of these suffer from tumours of the eye

or brain, or tumours in the head, neck, pelvis and

spinal area.

Clinical experience with protons has demon-

strated that the spatial precision of the irradiation

is often crucial to the successful result of the

therapy. Because the technique developed at PSI

provides a particularly high level of accuracy in the

irradiation, it has become the world-wide trendset-

ter for further developments in proton therapy.

Almost all facilities in planning or under construc-

tion today rely on the scanning technique, fi rst

used at PSI. As well as having the appropriate

accelerators and experienced staff, this success

has also been built on the interdisciplinary environ-

ment at PSI, and the particular background of

experience resulting from basic physical research.

The PSI team now has more than 25 years of

experience of proton therapy. By the middle of

2011, almost 6000 tumours of the eye and over

750 deep-seated tumours have been treated at

PSI. A therapeutic success rate of over 98 % cures

for irradiated melanoma of the eye is particularly

impressive. The results for the patients treated at

the proton gantry, about one third of them children

and young people, are also very encouraging, with

over 80 % tumour control in most cases.

Proton treatment of

deep-seated tumours

at Gantry 1.

A glimpse inside the COMET cyclotron (archive image taken during construction). Protons are accelerated to 180,000 kilometres per second along spiral-

shaped tracks from the inside to the outside of this machine.

7

Protonp+

Hydrogen atom

e– Electron

Positively-charged protons are building blocks of matter.

Hydrogen atoms have a nucleus containing one proton,

and free protons are achieved by ionising these atoms (the

electron is stripped away from the atomic shell).

P R O T O N T H E R A P Y AT P S I

The physics and engineering of proton therapy

Protons are elementary particles that carry a pos-

itive charge. As a result, they can be defl ected

within magnetic fi elds, bundled together and

formed into a beam as required. Unlike the photons

currently used in radiotherapy, protons are associ-

ated with a very defi nite, precisely limited depth

of penetration within the body. Photons emit their

maximum dose immediately after they have

entered the body. This means that healthy tissues

are also subjected to powerful radiation. The range

of protons depends on their initial speed and on

the material in which they stop. Only a relatively

low dose is absorbed in the material between the

surface of the body and the stopping point, and

the protons lose speed continuously as they travel.

At the end of their range, they stop and emit their

maximum dose, the Bragg peak. Behind this point,

the dose falls to zero within millimetres.

Protons therefore deposit their highest dose

of radiation directly inside the tumour, in the form

of a patch or a spot, and have a signifi cantly weaker

effect than photons on the healthy tissue between

the surface of the body and the tumour.

The diagram below shows the dose progression

for a single thin pencil beam of protons. The lower

part of the diagram also demonstrates that protons

emit a signifi cantly weaker dose than photons in

front of the target volume. Tissues behind the

target volume are signifi cantly irradiated by pho-

tons, while they are not affected at all by pro-

tons.

Photon

γ

Proton

p+

stops

Photons (electromagnetic waves) and protons (charged

particles) behave very differently from each other.

Target volume

Protons

Photons

100%

50%

10%

Depthcm0 10 20 30 40

Dose

Spot

Body surface

Individualprotonpencil beam

Bragg peak (spot)

The radiation dose of a proton pencil beam along its

penetration depth into the body. The range of these

protons is 25 cm. The dose distribution is shown above

as a contour, while dose values are shown along

the pene tration depth below, for comparison with the

behaviour of a photon dose.

The new compact COMET proton cyclotron at PSI in construction. This is the most compact proton therapy equipment of this type world-wide, and was

specifi ed by physicists at PSI. In the lower part of the picture, the stream of protons is extracted from the cyclotron and transported within a fraction of a

thousandth of a second to the treatment locations.

9

The PSI Spot-Scanning technique

Protons are accelerated in the COMET cyclotron

and focussed into a beam of approximately 5 to

7mm width (the spot). The protons are then

directed by magnets to the irradiation equipment,

known as the gantry, where they are guided

towards the patient and the tumour. These high-

dose spots cover the tumour in all three spatial

dimensions (the scanning). At Gantry 1, the pen-

etration depth of the proton spot is controlled by

a system of plastic plates that slide into the path

of the beam, and the movements only last for a

few milliseconds. Individual lines are irradiated in

the tumour, layer by layer, and the patient is moved

slowly in 5mm steps within the radiation area so

that all the spatial dimensions have been covered

by the spots. A more advanced scanning technique

will be used in the new Gantry 2: there, the beam

is simultaneously defl ected in two directions within

the tumour and the change of energy takes place

in the «Degrader» (attenuator), at the exit of the

cyclotron, all within a split second.

In the case of the treatment technique used at

PSI, the pencil beam of protons is controlled by

computers so that a high-dose spot is located very

accurately at the required position in the tumour

for a precisely pre-set time. By superimposing a

large number of individual spots – approximately

10,000 for a volume of 1 litre – the tumour can be

covered evenly by the required radiation dose,

while the dose is monitored individually for each

individual spot. This produces extremely precise,

homogenous radiation, with an optimum match to

the shape of the tumour (which is usually irregu-

lar). We call this dynamic, three-dimensional form

of radiotherapy the «Spot-Scanning technique».

It has been used to treat cancer patients at PSI

since 1996, is unique world-wide, and enables

tumours to be irradiated extremely accurately

while affecting the healthy surrounding tissue less

than conventional photon therapy.

D I E P R O T O N E N T H E R A P I E A M P S I

The principle of the spot-scan-

ning technique developed at PSI.

Dose distributions of any shape

can be produced by shifting and

superimposing the dose spot of

a proton pencil beam, and the

dose can be matched extremely

accurately in three dimensions

to the shape of the tumour.

This treatment plan demonstrates the particular precision

of the spot-scanning technique, using the example

of a brain tumour. The dose is matched individually in

each plane of the relevant boundary (yellow). The

tissue outside the tumour remains largely unaffected.

1

2

3

Above: Proton Gantry 1: A view from above onto the magnets in the gantry, which weigh many tons. They bundle and direct the proton beam to the

treatment location. The facility weighs over 100 tonnes and can be rotated as a whole precisely to the millimeter.

Below: This longitudinal section through Proton Gantry 1 shows the principle behind the way in which the proton beam is steered, and the position of

the three controlling elements: a defl ection magnet to defl ect the beam (1) (scanning), plastic plates to vary the penetration depth of the protons within

the body (2), adjustable patient table for layer-by-layer radiation (3).

11D I E P R O T O N E N T H E R A P I E A M P S I

Gantry 2 for the irradiation of movable tumours

Gantry 2 will enable this scanning technique to be

used to irradiate tumours extremely accurately,

even if they move during irradiation (e.g. lung or

breast tumours). In this gantry, the proton beam

is guided by defl ecting magnets in two dimensions

at a pre-set energy level into the tumour, and a

slice of the tumour is irradiated. The energy can

be changed in a fraction of a second to irradiate

the next layer of the tumour. The tumour is there-

fore «scanned» in three dimensions. Because of

the high speed at which the beam is defl ected and

the energy changed, the dose can be applied to

the tumour several times very quickly, and the

overall radiation time stays short. This repeated

«scanning» of the tumour volume allows the dose

to be distributed very evenly, even if the tumour

moves while it is being irradiated.

The Gantry 2 radiation station

during construction.

The drawing shows the overall technical facility for proton therapy at PSI. In the case of treatment for deep-seated tumours, the protons are accelerated

to approximately 180,000 kilometres per second in the COMET cyclotron accelerator. The accelerated protons are then directed by electromagnets via a

beamline in less than a thousandth of a second through a steel pipe that is practically free of air to the treatment stations (Gantry 1, Gantry 2 and

OPTIS 2), where they are guided into the patient’s tumour at a precisely pre-set energy and direction of irradiation. Computer control is used to ensure

that the proton beam deposits the pre-planned and pre-calculated dose, thus destroying the tumour cells.

Gantry 1

Gantry 2

Optis 2

COMET Cyclotron

Beamline

13D I E P R O T O N E N T H E R A P I E A M P S I

The proton therapy process at PSI

Proton therapy is administered in individual daily

fractions, just like conventional photon therapy,

and a course of treatment usually lasts six to eight

weeks (approx. 30 to 40 sessions). Most of the

patients are referred through university hospitals

and other hospitals in Switzerland and abroad,

and are then looked after by a qualifi ed team of

radio-oncologists, medical physicists and other

specialists at PSI. After producing an individual

mould to support the patient’s body, computer

tomography images are taken slice by slice. The

PSI medical team then establishes the dose bound-

ary for each plane of the tumour, i.e. the three-

dimensional target volume with a safety zone. This

forms the basis of the treatment plan, in which

computer programs developed specially for this

purpose at PSI pre-calculate, optimise and store

every setting of the radiation equipment in a data

set, together with the resulting dose distribu-

tion.

X-ray images are used to check the location of

the tumour and the patient’s position within their

individual moulded support at each treatment

session. Patients undergo regular follow-up checks

for several years after the course of treatment is

over.

The majority of patients are treated as out-

patients, though a few are accommodated in one

of the hospitals near to PSI. Infants are anaesthe-

tised during the individual treatment sessions, and

an anaesthetics team from the children’s hospital

in Zurich regularly attends infant treatment ses-

sions at PSI.

Patients are selected by the medical team at

PSI on the basis of the added medical value that

might be expected from the proton therapy from

experience. In Switzerland, the cost of treatment

for the following indications is currently paid by

the compulsory health insurance scheme:

• Intraocular melanomas (radiation for tumours

of the eye in the OPTIS facility)

• Meningiomas (benign and malignant), low-grade

gliomas

• Tumours in the area around the base of the skull

and in the ear, nose and throat region (ENT

tumours)

• Sarcomas, chordomas and chondrosarcomas

• Tumours in infants (including anaesthesia), chil-

dren and young people

Other indications are being investigated in trials

at PSI and at other centres.

A tumour in the head region of a 7-year-old child irradiated at PSI. Irradiation plan for radiation treatment using modern

conventional photon therapy (left) and using proton therapy at PSI (right). Irradiation by photons generates a «dose

bath» in a large part of the brain, and also affects the brain stem and optical nerves. This can be avoided by using proton

therapy.

Gantry 2 with integral 90° defl ecting magnet and radiation head (the person shown on the photo is not a patient).

15

Infants are anaesthetised for irradiation, so that the tumour position remains precisely fi xed. Proton therapy offers

particular advantages in their case, since an infant’s organism reacts particularly sensitively to radiation.

The medical team will need all the available

information, including previous investigations,

medical history and radiological documentation,

in order to prepare and implement a course of

proton therapy. Direct contact with the doctor

referring the patient is also very important to

ensure that good care is provided before and after

the therapy at PSI.

D I E P R O T O N E N T H E R A P I E A M P S I

Exact positioning of the patient is particularly important for proton therapy. This is ensured by a number of measures:

by providing individual moulded supports, fi tted to each patient’s body, by moving the patient table with extreme

accuracy, and by checking the position with CT (computer tomography) and X-ray images.

By mid-2011, more than 750 patients with

deep-seated tumours located near to critical

organs have been treated at Gantry 1. Almost 6000

patients with tumours of the eye have been suc-

cessfully irradiated at the OPTIS facility since 1984.

Since 2010, a new OPTIS facility (OPTIS 2) is avail-

able. Once Gantry 2 will go into operation (from

2012 on), about 500 patients with tumours will be

able to benefi t from proton therapy at PSI per year.

Impressum

Concept / Editing

Martin Jermann, PSI

Dagmar Baroke, PSI

Photography

Paul Scherrer Institut

H.R. Bramaz, Lieli

Alain Herzog, Source: ETH Board

Layout / Printing

Paul Scherrer Institut

Reproduction with quotation of

the source is permitted.

Please send an archive copy to PSI.

Order from

Paul Scherrer Institut

Communication Services

5232 Villigen PSI, Switzerland

Tel. +41 56 310 21 11

Internet

www.psi.ch

www.protontherapy.ch

Villigen PSI, September 2011

Paul Scherrer Institut, 5232 Villigen PSI, Switzerland

Tel. +41 56 310 21 11, Fax +41 56 310 21 99www.psi.ch, www.protontherapy.ch

PSI in brief

The Paul Scherrer Institute PSI is a research center

for the natural and engineering sciences. At PSI,

cutting-edge research is performed in the fi elds of

Matter and Materials, Human Health as well as

Energy and Environment. We use fundamental and

applied research to work on sustainable solutions

for key questions raised in society, science and

economy. With the equivalent of about 1400 full-time

staff positions, we are the largest research institute

in Switzerland. We develop, construct and operate

complex large-scale facilities. Every year about 2000

guest scientists from Switzerland and around the

world come to us. Just like PSI’s own researchers,

they use our unique facilities to carry out experi-

ments that are not possible anywhere else.

ContactsCentre for Proton Therapy

Administration

Tel. +41 56 310 35 24

protonentherapie@psi.ch

Contact person for journalists:

Dagmar Baroke

Tel. +41 56 310 29 16, Fax +41 56 310 27 17

dagmar.baroke@psi.ch

Pro

ton

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erap

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, 10/

2011