Fig. 1: Partial view of a proton therapy accelerator: The large red components are powerful magnets keeping the particles on a circular path, the yellow components are focusing elements, and the light blue/turquoise system at the right is the extraction system sending the particles from the accelerator to the patient.

Why protons?
Protons are positively charged particles – the nucleus of the hydrogen atom. Free protons are produced by removing the electrons from hydrogen atoms (ionization). The protons can then be accelerated to high speed using electric and magnetic fields. This is done in proton cyclotrons or synchrotrons, machines where the protons travel on circular orbits. Every time they pass by a given point in the machine they get a kick by an oscillating electric field – a little bit like a parent pushing the child on a swing to get it higher and higher.
In radiotherapy protons enter the human body at a pre-selected energy and continue in a nearly straight line up to a precisely predictable depth. While moving, they release very little energy, occasionally ionizing a target atom and thereby slowing down. Towards the end of their trajectory the protons have slowed down significantly and the likelihood of ionizing target atoms increases dramatically. The energy deposition rises sharply, and the protons come to rest at the Bragg peak (named after the physicist William Henry Bragg) where they release most of their energy. Behind the Bragg peak the dose reduces to zero within a few millimeters.
 This physical profile is the reason for using protons in radiotherapy. It permits deep-seated tumors to be treated without loading the healthy tissue in front of the tumor and without ever overshooting the mark.


How particle therapy works
If a charged particle, such as a proton, passes through a cancer cell, or comes to rest in it, the cell nucleus will be damaged by the energy deposited to the cell. Under certain circumstances, however, the cell is capable of repairing this damage. The challenge of radiation therapy is to administer the dose in such a way that tumor cells have no chance of repairing themselves, and, without exception, die off. Healthy cells, on the other hand, should suffer no major damage and be able to recover.


Shaping the beam to the shape of the tumor
To conform the proton beam to the often complex shape of the tumor, one method used traditionally consists of first increasing the beam diameter by passing it through a scatter system made from heavier materials where collisions of the protons with the target atoms deflect the proton trajectories sideways. Once the beam has reached a size larger than the tumor as seen from the beam direction one can use specially shaped masks to adapt the cross section of the beam to match exactly the tumor shape. To adapt the stopping point of the beam on the far side of the tumor one places a piece of material machined as a negative of the distal edge of the tumor (the bolus) in front of the patient. Where the beam has to penetrate the deepest, the bolus is at its thinnest. To make sure the Bragg peak is covering the entire thickness of the tumor in the direction of the beam a rotating wedge is used to change the energy and thereby the penetration depth of the beam.

Fig. 2: Passive scattering is one possibility to confirm the beam shape to the tumor. By widening the beam and sending it through special collimators the cross section of the beam is shaped to conform exactly to the shape of the tumor in radial direction. Using range modulators (materials with varying thicknesses) together with a compensator bolus (a block of material which is a negative imprint of the far edge of the tumor) the Bragg peak can be adjusted to optimum overlap with the axial dimension of the tumor.

The Proton pencil beam
As protons are elementary particles which carry a positive charge they can be deflected and focused in magnetic fields, and the beam can be shaped as desired. The most modern facilities today use a proton beam as thin as a pencil. By varying the energy the depth where the dose is delivered can be varied. By deflecting the beam sideways using magnetic fields one can ‘paint’ a complex picture at a given depth in the body – similar to generating a TV image with a single electron beam scanning across the screen line by line. Combining
these two methods (rapidly varying the energy of the beam and painting the tumor cross section slice by slice) any complex shape of a tumor can be covered. Using several proton beams entering from different directions one can even generate shapes with volumes in the center which do not receive any radiation (donuts). This is not possible at all using X-ray beams. Visit the w eb site of the Paul Scherer Institute in Zuerich, Switzerland for more information about this fascinating technology.

In active scanning the beam is deflected up and down and sideways using electric fields. In this way any arbitrary cross section of a tumor can be filled point by point much as when generating a TV picture by scanning an electron beam line by line across the screen (in a good old fashioned Television set). By starting with the farthest layer and then sequentially reducing the energy, layer after layer of the tumor can be irradiated until the entire volume of the tumor is treated.

The Bragg peak
The range of the protons depends on their initial speed and on the material in which they are absorbed. Between the surface of the body and the point where they stop, the material absorbs only relatively little energy (low dosage) through ionization of target atoms, causing the velocity of the protons to fall continuously. When the velocity of the protons decreases the likelihood of ionizing a target atom increases until the proton comes to a complete stop where they release their maximum energy. This generates a dosage peak, the so called Bragg peak. A few millimeter beyond this point the dose drops to zero.

Fig. 4: This figure shows in red the dose curve for a monoenergetic, thin pencil beam of protons. Through the weighted superposition of proton beams of different energies (Bragg peaks with different proton ranges) it is possible to deposit a homogenous dose in the target region. The resulting (range-modulated) proton beam distribution is called Spread Out Bragg Peak (SOBP and is shown in blue). The depth dose curve of an X-ray beam (the modality used today in most hospitals for radiation therapy), which shows the characteristic exponential decrease of the dose with depth is shown in green. The picture clearly shows that protons deposit a substantially smaller dose than X-rays outside the tumor. On the way to the tumor X-rays deposit substantially more dose than protons. Beyond the target volume the tissue is still irradiated significantly when using X-rays but receive absolutely no dose when using protons..

How much radiation dose?
The radiation dose is a measure of the energy absorbed in a material, such as body tissue. Its unit is the Gray [Gy] with 1 Gy being equivalent of 1 Joule/kilogram. A typical therapy dose for the destruction of a tumor amounts to approximately 60 to 70 Gy. It is transferred in individual fractions in several successive days (approx. 30 fractions in total).

The biological effect of radiation however, depends not only on how much energy is deposited in the cells, but also in what form the energy is deposited. Therefore the same dose of one radiation may have a different effect than another modality would have, which has lead to the definition of the Gray-Equivalent (GyE).