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Cancer
radiotherapy
Irradiation by other particles

Hadrontherapy groups together the utilisation of particles of the physical family of hadrons: protons, neutrons, pions and, by extension, ions.

The great mass of these particles (compared to photons or electrons), their charge or absence of charge together with their interaction with matter confer them with specific characteristics (biological and ballistic) which may be very useful in radiotherapy.

Protons

Protons interact with nuclei (nuclear interactions) and to a greater extent with electrons (electronic interactions).

As they are slowed down by their energy loss due to such interactions, the energy deposit per depth unit (or TEL) increases until the particle comes to a halt. There is therefore a sudden peak of energy (Bragg peak), situated at a depth which is in relation to the original energy. The skin dose to tumour dose ratio is approximately one to four.

Diagram of the energy deposit of electrons, photons and protons. It is clear that almost the entire energy of protons is liberated in a very narrow peak known as the Bragg peak.

Besides this very precise energy loss, the relative biological effect is far more important than for photons, due to the high number of interactions which occur in the mean depth of the DNA molecule (about 20 Å). Photon irradiation with a Cobalt source produces approximately 0.01 collisions during the crossing of this depth while protons produce 0.57 events. Heavy particles (such as Carbon Ions) will produce approximately 3 events, thus explaining the greater number of irreparable DNA lesions.

Protons can be produced by cyclotrons: they are injected at the centre of a magnet and are accelerated by magnetic and electric fields. Synchrotrons allow the variation of the proton energy. Protons are then reunited by several magnets in a quality beam to the irradiation target either via a direct beam or an isocentric gantry.

Main indications of protons are:

Neutrons

Neutrons are particles with indirect ionisation power. They interact with nuclei (elastic and inelastic diffusion, nuclear reactions, captures), which produce the emission of secondary charged particles (like protons, alpha particles of nuclear fragments heavier than carbon, oxygen, nitrogen or hydrogen) which are responsible for tissue ionisation and for the biological effect.

Interactions of neutrons with matter. Above: elastic diffusion with production of a proton and another neutron.

Below: collision of a nucleus with the production of various charged particles: protons, nuclear fragments, electrons.

The transfer of lineic energy is approximately 50 times higher than for a photon, however the deposit is similar to that of a photon (no Bragg peak).

The production of neutrons is based on cyclotrons which accelerate either deuterium (maximal energy 50 MeV) or protons (maximal energy 65 MeV) which collide with a target in beryllium producing a spectrum of neutrons.

There are very few indications for neutron therapy:

Another promising technique which is still in progress is therapy using boron neutron capture (BNCT): the tumour is saturated with 10B atoms because of the administration of boron to the patient. Neutrons are electively stopped by the boron, provoking a local nuclear fission in two atoms of 7Li and 4He.

This kind of experimental treatment is studied for highly radioresistant tumours such as brain glioblastoma.

Ions

They combine the ballistic properties of protons (energy deposit with Bragg peak, low lateral dispersion) and the biological properties of neutrons (elevated TEL, no oxygen effect): generally speaking, hadrontherapy involves treatment by ions.

Ions may be light like carbon, oxygen or even neon or they may be heavy such as argon or silicium.

Several studies are in progress. The French government has decided, within the framework of its cancer plan, to build an experimental facility in Lyon, although another project exists in Caen, within the vicinity of a Heavy Ion Facility (GANIL). Other countries already possessing or currently building hadrontherapy facilities are Japan, Germany, Italy and Austria.

The production of light ions requires the presence of a synchrotron to accelerate the ions using various energies. Many technical difficulties remain such as the construction of an isocentric gantry (as in standard radiotherapy).

The tumour margin may be accurately drawn by the beam using active raster scanning: every point of the tumour slice is treated (i.e. the Bragg peak targets this point), then another slice is treated by varying the beam energy.

Principle of raster scanning: in [1] each tumour slice is scanned by the Bragg peak and receives high and precisely localised energy. The lateral and vertical movements are brought about by variations in electromagnetic fields. In [2], once the slice treated, the beam energy is modified and another slice is treated.

Another interest characteristic of carbon ions would be the theoretical possibility of obtaining in vivo dosimetry: where ions deposit energy, positrons are produced and can be detected by PET-Scan.

The potential indications of this treatment would be:

  • tumours of the base of the skull,
  • facial sinus tumours,
  • meningeal tumours inaccessible to surgery,
  • paraspinal tumours,
  • deep sarcoma,
  • and perhaps many forms of radioresistant tumours.
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