The radiation response of heterogeneous tumors.

Heterogeneous tumors often have a wide spectrum of radiation sensitivities due to factors like their genetic make up, clonal distribution and degree of genetic instability, as well as gradients of oxygen and nutrients. Recent studies demonstrate that the radiation response of heterogeneous tumors can be rather well described by a single effective clonogen compartment when the dose-response relation at high doses is of main interest. When a correct description of the clonogen survival is important at both low and high doses, a description based on one sensitive and one resistant clonogen compartment will be necessary and generally sufficient and surprisingly accurate. Such a description is valuable for example when in vivo PET-CT data are acquired early in the treatment to predict the required curative radiation dose. Methods are given for derivation of the sensitive and resistant cell compartments based on clinically observed dose-response relations and the degree of hypoxia. Principal characteristics of heterogeneous tumors are derived, such as the dose D(t) describing the transition when sensitive cells are lost and resistant cells start to dominate the response resulting in a fast change in slope of the cell survival curve. Since the effective compartments are based on the whole spectrum of radiation resistance, they will take both low intermediate and high sensitivity values into account, thus providing an accurate description of the radiation response over the entire range of clinically relevant doses.