Broad-shouldered survival curves of a human melanoma xenograft. Implications for radiation therapy in the absence and presence of misonidazole.

A human malignant melanoma (E.E.) was irradiated in vivo in athymic nude mice, with subsequent assay of single cell survival in vitro. By assuming the survival curves for the hypoxic as well as for the aerobic cells in the tumour to be of the form S = exp(-D/D1) X (1-[1-exp (-D/D2]n), theoretic survival curves were fitted to the experimental data for tumours irradiated in air-breathing mice. Assumptions were made about hypoxic fraction, oxygen enhancement ratio, sensitization by misonidazole, repair of potentially lethal damage, and reoxygenation, all based upon own experimental data on E.E. melanoma. Theoretic surviving fractions were calculated for several clinically relevant fractionation regimes, both for irradiation in the absence and in the presence of misonidazole. The results indicate that tumours with biologic parameters like those of E.E. melanoma are best treated with fractionation regimes with few fractions and high doses per fraction, whether misonidazole is present or not.