Modeling the biological effects of heavy ion radiation

The application of ion beams in tumor therapy requires the precise knowledge of their biological effects. Due to the complex dependencies of the effectiveness on e.g. ion species, beam energy, dose and cell- or tissue type the effectiveness cannot be determined for all relevant situations on an experimental basis. Therefore, we have developed a biophysical model called 'Local Effect Model' (LEM). The name indicates, that the calculation of the biological effects is based on the local energy deposition within the cell nucleus. A typical distribution is shown in fig. 1 (lower left), characterized by extremely high local doses at the positions where particles are traversing the cell, whereas the dose levels between the trajectories are on a moderate level. In contrast, the corresponding distribution for conventional photon radiation is homogenous (upper right figure).

Abb. 1

Dose distribution of ion beams compared to photon beams  

The Local Effect Model (LEM) is based on the calculation of biological effects in small subvolumes of the cell nucleus. In such a small subvolume, the dose distribution can be regarded as homogenous, similar to the distribution of photons (lower right). Therefore, the biological effect in this subvolume is expected to be similar to the effects of photons a the same dose level. By integration over all subvolumes of the cell nucleus, the effectiveness of ion radiation can be predicted on the basis of the experience achieved with conventional photon radiation.

Fig. 2 shows, that the model allows accurate predictions of the biological effects of ion radiation. Calculated survival probabilities are compared here with experimental data as a function of the penetration depth of a 170 MeV/u carbon ion beam. The small effects on the first few centimeters as well as the drastic increase of the effect in the Bragg peak region are correctly reproduced.

Abb. 2

 Comparison of simulation and experimental data: Irradiation of CHO cells with 170 MeV/u carbon ions

Besides in-vitro cell survival data, the model has been tested also by comparison with in-vivo animal experiments. This was an important task before therapy with ion beams started, because complex tissues might respond differently to radiation than cell cultures. But also in these cases in general sufficient agreement was observed. This opened the way to implement this type of biophysical modeling in the treatment planning procedure for carbon ion therapy.

Recently, the Local Effect Model was modified in order to improve the accuracy of its predictions, especially for the ratio of high to low LET particles. Therefore, the additional damage by clustered single strand breaks was included into the calculations as well as a refinement of the radial dose ditribution around the ion tracks.

contact: m.scholzgsi.de

Selected Publications: 

Elsässer Th. , Scholz M. Cluster Effects within the Local Effect Model, Rad. Res. 167, 319-329 (2007)

Scholz M and Kraft, G. The physical and radiobiological basis of the local effect model: A response to the commentary by R. Katz. Rad. Res. 161, 612-620 (2004) Abstract

Scholz, M, Kellerer, AM, Kraft-Weyrather, W, Kraft, G. Computation of cell survival in heavy ion beams for therapy - the model and its approximation. Radiat. Environ. Biophysics  36, 59-66 (1997)  Abstract

Scholz, M. Calculation of RBE for normal tissue complications based on charged particle track structure. Bull. Cancer Radiother. 83 Suppl., 50s-54s (1996)  Abstract

Scholz, M., Kraft, G. Track structure and the calculation of biological effects of heavy charged particles. Adv. Space Res. 18,  5-14 (1996)  Abstract

Scholz, M., Kraft, G. Calculation of heavy ion inactivation probabilities based on track structure, x-ray sensitivity and target size. Radiat. Prot. Dosim. 52, 29-33 (1994)