Influence of cellular radiation sensitivity on local tumor control of human melanoma xenografts given fractionated radiation treatment

The radiocurability of human melanoma xenografts was studied by treating tumors with multiple fractions of 2.0 Gy and using local tumor control at 180 days as end point. Three melanoma lines (E. F., G. E., M. F.) that are only weakly immunogenic in athymic nude mice (BALB/c-nuνBOM) were selected for the study. The tumor radiocurability was found to differ considerably among the lines; the radiation doses required to achieve local control of 50% of the tumors irradiated (TCD50s; mean ± SE) were 85.0 ± 4.7 Gy (E.F.), 60.3 ± 5.4 Gy (G.E.), and 99.3 ± 5.7 Gy (M. F.). The radiation sensitivity in vitro of cells isolated directly from tumors also differed significantly among the lines. The TCD50 showed positive correlations with the surviving fraction after 2.0 Gy in vitro, the surviving fraction after two doses of 2.0 Gy (4-h interval) in vitro, and the surviving fraction after 4.0 Gy at a low dose rate (1.25 cGy/min) in vitro. Thus, the differences in tumor radiocurability among the lines were mainly a consequence of cellular differences in the capacity to repair radiation damage. Comparisons of measured TCD50s with theoretical TCD50s, calculated from cell-surviving fractions measured in vitro after radiation treatment in vitro or in vivo, suggested that other tumor parameters, e.g., rate of population between radiation fractions, also had a significant impact on the TCD50. However, this study strongly supports the assumptions that the surviving fraction at 2.0 Gy in vitro is a useful parameter for prediction of clinical tumor radiocurability