The effect of fractionated carbon-ion beams to tumor metastasis

[Background and Purpose] The fractionated irradiation is standard protocol for radiotherapy including carbon-ion beam (C-ions) therapy. There are big differences between single and fractionation, for example on DNA damage repair, reoxygenation of hypoxic region, etc. It is necessary to get the results using fractionated irradiation to know the effects in clinical. The purpose of this study is to examine the effects of fractionated irradiation for metastasis using C-ions and X-rays. [Materials and Methods] A mouse osteosarcoma cells, LM8 having highly metastatic potential were used. C-ions irradiation (290 MeV/u) was performed at the center position of 6cm-SOBP, and X-rays were used as reference beam. The interval among each fraction was 24 hours, and 1 to 5 fractions were used. [in vitro] The cytotoxic effects were examined using colony formation assay, and the anti-metastatic effects were examined by the inhibition of migration and invasion activities using Boyden chamber assay and Matrigel invasion assay, respectively. [in vivo] LM8 tumors inoculated into right hind leg of mice were irradiated at 12days after inoculation. Radiosensitivity for individual cell in a tumor was examined by in vivo-in vitro assay. The metastatic effects were analyzed with the spontaneous lung metastasis model. [Results] [in vitro] After X-rays fractionation, cell survival and metastatic potentials (migration and invasion activities) were increased depend on the fraction number, and the degree was significant at low dose region. On the other hand, the enhancement was not significant after C-ions fractionation. [in vivo] The survival of cells in local tumor and the number of lung metastatic nodules were increased with the increment of the fraction number after fractionated irradiation. The degree of increase was more remarkable by X-rays than C-ions. The RBE values of C-ions were increased with fraction number on both cell killing and suppression of metastasis, and the values were larger on metastasis suppression than on cell killing. [Conclusion] It is confirmed that the anti-metastatic effects showed the dependency of the fraction number as well as cell killing effects. The degree of the dependency was more significant for X-rays compared with C-ions with high LETs than X-rays with low LETs. It was suggested that C-ions therapy was superior to photon therapy not only on tumor cell killing but also on metastasis suppression even for clinical fractionated irradiation.
39th Annual Meeting of the European Radiation Research Society