Microdosimetric description of beam quality and biological effectiveness in radiation therapy.

Modern radiation therapy includes dosimetric and biological optimization methods aiming to improve the tumour control probability and reduce the unwanted reactions in healthy tissues. From this point of view the quality of the radiation beam is an important parameter that is not generally taken into account in clinical practice. The beam quality depends largely on the macroscopic absorption and scatter of the incident radiation but also on the microscopic fluctuations in the specific energy imparted within the cell nuclei in the patient. The radiation effect depends also on the complexity of the induced damage, the ability of the cells to control cell cycle progress and the efficiency and fidelity of the repair system. Therefore the conventional macrodosimetric quantities have to be complemented with microdosimetric quantities for an accurate description of the quality properties of the radiation beam. It is demonstrated that the DNA damage produced by sub keV electrons and high LET particles has a high probability to be lethal for the cell. These electrons may generate closely spaced double strand breaks or more general 'multiply damaged sites'. Such severely damaged sites may partly be due to the geometrical arrangement of double coiled DNA on the nucleosomes or triple coiled DNA in the cromatin fibre. This kind of damage has a large probability to be misrepaired when the DNA is opened up for repair and may therefore later result in cell death. Furthermore, it is shown that the reduced biological effect at ultra high LETs (> 200 eV/nm) and at ultra short pulses of high dose rate low LET radiation most likely is due to increased radical-radical recombination in the 10 nm-10 ns domain. Based on microdosimetric measurements, significant quality variations in conventional therapeutic beams are detected particularly close to inhomogeneities, in the build-up region or in the presence of high LET contamination. These variations influence the biological effectiveness of the radiation beam and the steepness of the dose-effect relation, thus affecting in some cases the clinical radiotherapeutic outcome. It is shown that such effects may also explain the limited success of most trials with high LET radiations. A serious consideration of beam quality variations in treatment planning algorithms combined with dosimetric and radiobiological optimization of the treatment techniques may increase the probability of tumour control and minimize the unwanted acute and late reactions in healthy normal tissues.