In Vivo Cell Survival and Volume Response Characteristics of Rat Rhabdomyosarcoma Tumors Irradiated in the Extended Peak Region of Carbon- and Neon-Ion Beams

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Abstract
Cell survival was measured for rat rhabdomyosarcoma R1 tumor cells irradiated in the distal 4-cm peak region of 400 MeV/u C- and N-ion beams. An in vitro assay for clonogenic capacity was used to determine the surviving fraction of cells following in vivo tumor irradiation. Based on the response to 225-kV X-rays under air-breathing and hypoxic conditions, it was estimated that the chronically hypoxic fraction of cells is 35%. From survival curves for tumors irradiated in air-breathing rats, RBE0.1 values determined at the 10% survival level were 2.0 and 3.1 for the peak C and N-ion radiation, respectively. Under hypoxic conditions, RBE0.1 values for peak C and N ions were, respectively, 2.0 and 3.3. A diminished oxygen effect was observed for the N-ion relative to the C-ion radiation. Values of RBE [relative biological effectiveness] for the 2 heavy charged-particle beams were determined from measurements of tumor regression and regrowth following irradiation. Based on the ratio of X-ray to charged-particle doses required to produce a growth delay of 50 days, RBE50 values for peak C and N ions were 2.3 and 2.9, respectively. These RBE values are similar to those obtained in the cell survival studies and, to the extent that they reflect a large population of hypoxic cells, indicate that peak N ions have a greater therapeutic potential than peak C ions for the treatment of radioresistant hypoxic tumors.

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