The clinical significance of ratios of radiobiological parameters

Purpose: Interindividual heterogeneity of the radiobiological characteristics of malignant and normal tissues hampers the derivation of radiobiological parameters from clinical data, Focusing on the ratio Dprolif, i.e,, the dose to compensate 1 day of treatment interruption, this article investigates the hypothesis that ratios of parameters might be less sensitive to interpatient heterogeneity and may constitute a more reliable description of the radiobiological properties of tissues than the parameters themselves. Methods and Materials: Analytic calculations were performed in an idealized example in which the only source of heterogeneity was the number of clonogenic cells, Computer simulations were used to assess the effects of heterogeneity in radiosensitivity and in proliferative capacity, Treatment outcome was simulated in pseudopatients with increasing dose-time correlation. Results: Interindividual heterogeneity in clonogenic cell number, radiosensitivity, or proliferative ability results in a marked underestimation of the response parameters describing these processes. In contrast, the estimates of the ratio Dprolif were more stable. The coefficients of variation increased with increasing heterogeneity. However, this only became unacceptable when heterogeneity in radiosensitivity was marked, or when total dose and treatment time were closely correlated. Conclusion: Parameter ratios may provide more robust radiobiological information than single parameters estimated from clinical data except when interindividual heterogeneity is very large or when the treatment modalities are too highly correlated. As usual, caution is advised in the presence of patient selection, a correlation between treatment prescription and expected outcome, or limited ranges of dose-time treatment patterns.