Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern

Purpose: To present details of the recent version of the 'Local Effect Model' (LEM), that has been developed and implemented in treatment planning for the ion beam therapy pilot project performed at GSI Helmholtzzentrum fur Schwerionenforschung in Darmstadt, Germany. Materials and methods: The new version of the model is based on a detailed consideration of the spatial distribution of the initial damages, i.e., double-strand breaks (DSB). This spatial distribution of DSB is obtained from the radial dose profile of the ion track using Monte Carlo methods. These distributions are then analyzed with regard to the proximity of DSB. This version of the model also facilitates the calculation of full dose response curves up to arbitrary high doses, thus allowing to thoroughly check the approximations previously used to estimate the quadratic term (beta-term) for the linear-quadratic description of dose response curves. Results: The accuracy of the model predictions is demonstrated by good agreement of the relative biological effectiveness (RBE) as a function of the linear energy transfer (LET) with experimental data obtained for V79 cells after carbon irradiation. The beta-values predicted by the full simulation tend to be larger as compared to the approximation in the intermediate LET range. Conclusion: The new version of the model allows a more mechanistic description of the biological effects of ion radiation. The full simulation is a prerequisite for tests of the validity of the approach at high doses, which are of particular interest for application in hypofractionation studies.