Biologically optimized radiation therapy

Advanced treatment optimization is possible using quantitative radiobiologi cal dose response models. Although all present models are necessarily linke d to a certain degree of uncertainty, this will only have a small influence on the relative shape of the resultant optimal dose distribution. However the exact dose level should perferably be determined clinically by dose esc alation with the optimized dose plan as a control arm. It is shown that a l arge part of the biological effect of high linear energy transfer radiation is due to the spectrum of low-energy delta -electrons that can generate de nse clusters of complex DNA damage. Such electrons are efficiently generate d by low-energy photons or densely ionizing ion beams and to a considerably smaller degree by high-energy electrons, photons and protons. A new analyt ical expression is developed for the effective radiation resistance of hete rogeneous tumors, making it possible to approximate the response of such tu mors by the effective clonogen number N-0.eff and the effective D-0 value D -0.eff. It is shown that a relatively small number of resistant tumor cells may well be sufficient to dominate the response of hypoxic or otherwise he terogeneous tumors. Finally, several examples are given of intensity-modula ted dose distributions generated by multiple radiation modalities, the tota l effect of which is biologically optimized.