Significance of fractionated irradiation for the biological therapeutic gain of carbon ions.

It is well established that the RBE (relative biological effectiveness) for cell killing depends on LET (linear energy transfer), and that a maximum RBE is observed at approximately 150 keV.micron-1. However, the therapeutic gain depends on the ratio of the RBEs for the effects on the cancer cell population and the effects on normal tissues. The RBE of a given radiation quality depends not only on LET but also on dose, biological system and effect, and irradiation conditions. There is no data available to answer the question: which LET is suitable to improve the biological therapeutic gain of carbon ions? Here, three different LET values of 290 MeV/u carbon ions were selected, and the relative biological effectiveness was compared between tumour-growth retardation and skin damage using a murine transplantable tumour. Larger RBE values for tumours after than the skin type were obtained when carbon ions of intermediate LET were delivered daily for 2 to 5 fractions. The biological therapeutic gain would be high for the carbon ion SOBP if the number of fractions were correctly selected in clinical trials.