Biophysical modelling of proton radiation effects based on amorphous trackmodels

Purpose: To define a photon-equivalent dose in charged particle therapy one needs to know the RBE (Relative Biological Effectiveness) in the target re gion as well as in the surrounding tissue. RBE estimates are difficult sinc e both the physical input parameters, i.e. LET distributions, and. even mor e so, the biological input parameters, i.e. cell nucleus size and local res ponse, are not known in general. Track structure theory provides a basis fo r predicting close response curves for particle irradiation. There are (at least) two somewhat different algorithms: the Amorphous Track Partition mod el (ATP) and the Amorphous Track Local effect model (ATL). Both have been r eported to give good agreement with observed radiobiological data. Ve were interested in a general comparison and in the predictive power of these mod els for protons. Materials and methods: We compared the principles of the two track structur e approaches. The general dependencies of the model predictions on the inpu t parameters are investigated. The model predictions for protons with respe ct to cell survival of V79 cells are compared with measurements. Results: Although based on similar assumptions, the application of track st ructure theory in terms of the computational procedure is different for the two models. The ATP model provides a set of equations to predict inter- an d intratrack radiation response,whereas the ATL model is based on Monte Car lo simulations. One conceptual difference is the use of average doses in su btargets in the ATP model compared with the use of local doses in infinites imal compartments in the ATL model. The ATP concept introduces an empirical scaling of the cross-section from subcellular to cellular response. The AT L concept inherently requires a critical adjustment of parameters handling the high local dose region near the track centre. The models predict proton survival curves reasonably well but neither shows good agreement With expe rimental data over the entire range of proton energy and absorbed dose cons idered. Conclusion: Designed for heavy ion applications, the models show weaknesses in the prediction of proton radiation effects. Amorphous track models arc based on assumptions about the properties of the biological target and the radiation field that can lie questioned. In particular, the assumption of s ubtargets and the multitarget/single-hit response function on one hand and the parameterization of radial dose and high dose cellular response on the other hand leave question marks.