THE CLINICAL-SIGNIFICANCE OF RATIOS OF RADIOBIOLOGICAL PARAMETERS

Purpose: Interindividual heterogeneity of the radiobiological characte ristics of malignant and normal tissues hampers the derivation of radi obiological parameters from clinical data, Focusing on the ratio Dprol if, i.e,, the dose to compensate 1 day of treatment interruption, this article investigates the hypothesis that ratios of parameters might b e less sensitive to interpatient heterogeneity and may constitute a mo re reliable description of the radiobiological properties of tissues t han the parameters themselves. Methods and Materials: Analytic calcula tions were performed in an idealized example in which the only source of heterogeneity was the number of clonogenic cells, Computer simulati ons were used to assess the effects of heterogeneity in radiosensitivi ty and in proliferative capacity, Treatment outcome was simulated in p seudopatients with increasing dose-time correlation. Results: Interind ividual heterogeneity in clonogenic cell number, radiosensitivity, or proliferative ability results in a marked underestimation of the respo nse parameters describing these processes. In contrast, the estimates of the ratio Dprolif were more stable. The coefficients of variation i ncreased with increasing heterogeneity. However, this only became unac ceptable when heterogeneity in radiosensitivity was marked, or when to tal dose and treatment time were closely correlated. Conclusion: Param eter ratios may provide more robust radiobiological information than s ingle parameters estimated from clinical data except when interindivid ual heterogeneity is very large or when the treatment modalities are t oo highly correlated. As usual, caution is advised in the presence of patient selection, a correlation between treatment prescription and ex pected outcome, or limited ranges of dose-time treatment patterns.