Fractionation sensitivity (alpha/beta ratio) of human melanoma xenografts.

Abstract

The fractionation sensitivity (alpha/beta) of ten human melanoma xenograft lines was measured in vivo and related to cellular radiation sensitivity measured in vitro. Xenografted tumours were irradiated under clamped conditions with 2, 4, 8 or 16 fractions within a constant overall treatment time of 5 days. At least three different fractional doses were used for each schedule. Tumour regrowth delay was used as endpoint. Isoeffective total doses were determined from plots of tumour regrowth delay versus total radiation dose and subjected to FE analysis for the determination of alpha/beta values. Single cell suspensions prepared by disaggregation of xenografted tumours were irradiated in vitro. Cell survival was measured by using the Courtenay soft agar colony assay. The alpha/beta ratio in vivo, divided by an oxygen enhancement ratio of 2.8, ranged from 1.0 +/- 0.2 Gy to 33.0 +/- 6.7 Gy. Seven lines showed alpha/beta values similar to or higher than those of acutely responding normal tissues. The alpha/beta values of the remaining three lines were similar to or lower than those of late responding normal tissues. The alpha/beta ratio in vivo showed statistically significant correlations to the alpha/beta ratio and the cell surviving fraction at 2.0 Gy (SF2) in vitro. High alpha/beta values in vivo corresponded to low SF2 values in vitro. Optimum radiation therapy of malignant melanoma requires an individualized treatment strategy. SF2 values measured in vitro might be useful guidelines for selection of the optimum fractionation schedule.