How To Treat Cancer With Proton Therapy

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1 Proton therapy at the Paul Scherrer Institute

2 PSI proton therapy for tumours of the eye (OPTIS). The patient s head is fixed 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.

3 3 Proton therapy at the Paul Scherrer Institute 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 radiation 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 first time in This was the first installation of this type anywhere in Europe. The first proton gantry for the irradiation of deepseated tumours was taken into service at PSI in 1996, and was also the first 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. 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 benefited from this therapy at PSI.

4 4 PROTON THERAPY AT PSI Radiotherapy and its significance 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 five 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 precisely as possible, and that the healthy areas of the body should be irradiated as little as possible. This can significantly 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 therefore used to fight against tumours that are limited to a specific location. It is not interchangeable with therapies that have to act on the whole body (systemic therapies), such as chemotherapy and immunotherapy (especially for the treatment of metastases). In radiation therapy, the tumour cells are destroyed by x-ray or gamma radiation (photon therapy) or by particle radiation (e.g. proton therapy). 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. Nevertheless, proton therapy can help to achieve significantly better results for certain tumour indications and tumour localisations. The developments at PSI also demonstrate that the potential for improvement is still far from exhausted. How does radiotherapy work? 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 justifiable treatment costs 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. 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 difficulty. 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).

5 PROTON THERAPY AT PSI 5 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 first time at the Lawrence Berkeley Laboratory in California (USA) in 1954, and the first proton therapy programme in Europe ran in Uppsala (Sweden) between 1957 and In 1961, the Harvard Cyclotron Laboratory and the Massachusetts General Hospital in Boston, USA, started a proton therapy project. Melanoma of the eye was treated with protons for the first time in Europe in 1984, at the OPTIS facility developed especially for this purpose at PSI. The first proton therapy facility to be used at a hospital went into operation at the Loma Linda University Medical Center, California, in Following a development and testing phase of almost 10 years, up to 1500 patients have routinely benefited from proton therapy there since Today there are more than 35 centers in operation worldwide, 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 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 worldwide. 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 demonstrated 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 trendsetter for further developments in proton therapy. Almost all facilities in planning or under construction today rely on the scanning technique, first used at PSI. As well as having the appropriate accelerators and experienced staff, this success has also been built on the interdisciplinary environment 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.

6 A glimpse inside the COMET cyclotron (archive image taken during construction). Protons are accelerated to 180,000 kilometres per second along spiralshaped tracks from the inside to the outside of this machine.

7 PROTON THERAPY AT PSI 7 The physics and engineering of proton therapy Hydrogen atom e Electron Protons are elementary particles that carry a positive charge. As a result, they can be deflected within magnetic fields, bundled together and formed into a beam as required. Unlike the photons currently used in radiotherapy, protons are associated with a very definite, 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 significantly weaker p+ Proton 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). 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 significantly weaker dose than photons in front of the target volume. Tissues behind the target volume are significantly irradiated by photons, while they are not affected at all by protons. Body surface γ Individual proton pencil beam Target volume Spot Photon 100% Photons p + Dose 50% Bragg peak (spot) Proton stops Protons 10% cm Depth Photons (electromagnetic waves) and protons (charged particles) behave very differently from each other. 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.

8 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 specified 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 DIE PROTONENTHERAPIE AM PSI 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 highdose spots cover the tumour in all three spatial dimensions (the scanning). At Gantry 1, the penetration 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 deflected 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 irregular). 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. 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. The principle of the spot-scanning 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.

10 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 deflection magnet to deflect 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)

11 DIE PROTONENTHERAPIE AM PSI 11 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 deflecting 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 therefore «scanned» in three dimensions. Because of the high speed at which the beam is deflected 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.

12 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. COMET Cyclotron Beamline Optis 2 Gantry 1 Gantry 2

13 DIE PROTONENTHERAPIE AM PSI 13 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 qualified 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 boundary for each plane of the tumour, i.e. the threedimensional 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 distribution. 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 outpatients, though a few are accommodated in one of the hospitals near to PSI. Infants are anaesthetised during the individual treatment sessions, and an anaesthetics team from the children s hospital in Zurich regularly attends infant treatment sessions 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), children 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.

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

15 DIE PROTONENTHERAPIE AM PSI 15 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. 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 successfully irradiated at the OPTIS facility since Since 2010, a new OPTIS facility (OPTIS 2) is available. Once Gantry 2 will go into operation (from 2012 on), about 500 patients with tumours will be able to benefit from proton therapy at PSI per year. Exact positioning of the patient is particularly important for proton therapy. This is ensured by a number of measures: by providing individual moulded supports, fitted 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. 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 Infants are anaesthetised for irradiation, so that the tumour position remains precisely fixed. Proton therapy offers particular advantages in their case, since an infant s organism reacts particularly sensitively to radiation. Internet Villigen PSI, September 2011

16 Protonentherapie_e, 10/2011 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 fields 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 experiments that are not possible anywhere else. Contacts Centre for Proton Therapy Contact person for journalists: Administration Dagmar Baroke Tel Tel , Fax protonentherapie@psi.ch dagmar.baroke@psi.ch Paul Scherrer Institut, 5232 Villigen PSI, Switzerland Tel , Fax