Relative Biological Effectiveness of Carbon Ions in a Rat Prostate Carcinoma In Vivo: Comparison of 1, 2, and 6 Fractions

Purpose: To determine the relative biological effectiveness (RBE) and the effective alpha/beta ratio for local tumor control of a radioresistant rat prostate tumor (Dunning subline R3327-AT1) after 6 fractions of carbon ions and photons. Methods and Materials: A total of 82 animals with tumors in the distal thigh were treated with 6 fractions of either photons or carbon ions, by use of increasing dose levels and a 2-cm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for dose at 50% tumor control probability were used to determine RBE values. Including data for 1 and 2 fractions from a previous study, we estimated alpha/beta ratios. Results: For 6 fractions, the values for dose at 50% tumor control probability were 116.6 +/- 3.0 Gy for photons and 43.7 +/- 2.3 Gy for carbon ions and the resulting RBE was 2.67 +/- 0.15. The a/b ratio was 84.7 +/- 13.8 Gy for photons and 66.0 +/- 21.0 Gy for carbon ions. Using these data together with the linear-quadratic model, we estimated the maximum RBE to be 2.88 +/- 0.27. Conclusions: The study confirmed the increased effectiveness of carbon ions relative to photons over the whole dose range for a highly radioresistant tumor. The maximum RBE below 3 is in line with other published in vivo data. The RBE values may be used to benchmark RBE models. Hypoxia seems to have a major impact on the radiation response, although this still has to be confirmed by dedicated experiments. (C) 2013 Elsevier Inc.