Clinical Interest in Determinations of Cellular Radiation Sensitivity

Abstract

Determinations of cell sensitivity in terms of survival fraction after doses employed in clinical radiation therapy, say 1-3 Gy, are of increasing interest to clinicians as they provide direct experimental data which can be employed without reference to models of cell inactivation. SF2 values are expected ultimately to prove valuable as response predictors. Even so, SF2 values would surely be combined with other predictors also under development to give the best feasible estimate of response of tumor and normal tissue. There are, however, several concerns with the SF2 data currently available. These include: SF2 depends upon the cell system employed (established cell lines vs primary cultures) and the method of assaying survival fraction (colony formation vs population growth); dose-response curves for inactivation of tumors characterized by the reported distribution of SF2 values are, in many instances, not close to those judged to obtain in clinical practice; the broad distribution of SF2 values indicates a rather flatter dose-response curve for tumor control or normal tissue than seems true from clinical experience. There appears to be a potential for clinical gain by determination of sensitivity of normal tissues in order to identify patients who are of increased sensitivity (for example heterozygotes for AT, 5-oxoprolinuria, etc.). Although the absolute SF2 values obtained by current technologies of culturing human cells often appear to be poorly related to values expected from observed radiation response in patients, intensive research on cell viability assays will almost certainly yield more realistic results.