Radiobiological Characterization of Clinical Proton and Carbon-Ion Beams

Electromagnetic radiation (photons) or particle beam (protons or heavy ions) have similar biological effects, i.e. damage to human cell DNA that eventually leads to cell death if not correctly repaired. The biological effects at the level of organs or organisms are explained by a progressive depletion of constitutive cells; below a given threshold, cell division is no longer sufficient to compensate for cell loss, up to a point where the entire organism (or organ) breaks down. The quantitative aspects of the biological effects are modulated by the microscopic distribution of energy deposits along the beam or particle tracks. In particular, the ionization density, i.e. the amount of energy deposited by unit path length (measured in keV/μm), has an influence on the biological effectiveness, i.e. the amount of damage per energy unit deposited (measured in gray or Gy, equivalent to 1 joule/kg). The ionization density is usually represented by the Linear Energy Transfer or LET, also expressed in keV/μm. Photon beams (X-rays, g-rays) are low-LET radiation, with a sparsely ionising characteristic. Particle beams have a higher LET, with a more dense distribution of energy deposits along the particle tracks. Protons are intermediary, with a LET larger than the photon one, but still belong to the ‘radiobiological’ group of low LET. The higher the ionization density, the higher the biological effectiveness per unit of dose. When comparing various radiation qualities, it appears that the ionization density is relatively homogeneous along photon tracks, whereas it strongly varies along particular tracks (protons, heavy ions). In the first instance, the biological effectiveness is proportional to the TEL, itself dependant on the particle beam energy. So, when the LET of a particle beam is increased, its biological effectiveness increases in proportion. Secondly, a low-energy beam (f.i. 4 MeV a rays) has a higher LET than a high-energy beam (f.i. 200 MeV a rays). As particle beams continuously loose their energy through their successive interactions with the irradiated medium, it ensues that the LET slowly increases along the beam path, down to a point where all energy has been imparted and the beam stops. Therefore, the biological effectiveness is not homogeneous along the beam path (like with low-LET radiation), with a strong reinforcement at the end of the particle tracks (in the Bragg peak). The modelization of the clinical effects of particle beams is therefore very challenging, as a variable biological weighting function needs to be incorporated in the planning process to account for the increase in biological effectiveness with the progressive loss of beam energy.