A review of time-dose effects in radiation therapy

A historical review of conventional fractionation offers little confidence that such treatment is optimal for all tumors. Thus manipulation of time-dose schedules may provide a relatively inexpensive yet potentially useful technique for improving therapeutic results in radiation therapy. Consideration of basic radiobiological principles and animal model data illustrates the complex and heterogeneous nature of normal tissue and tumor response to time-dose effects and supports the hypothesis that better time-dose prescriptions can be found in clinical practice. The number of possible time-dose prescriptions is very large, and a review of the clinical trials using nonconventional fractionation demonstrates that the sampled portion of the total three-dimensional space of time, fraction number, and dose has been very small. Only carefully designed clinical trials can establish the therapeutic advantage of a new treatment schedule, and methods for selecting the most promising schedules are discussed. The use of simple data reduction formulas for time-dose effects should be discarded since they ignore the very complexity and heterogeneity of tissues and tumors which may form the basis of improved clinical results.