The volume effect in radiotherapy--its biological significance

Volume-related effects are an important consideration in clinical radiotherapy. The early rationale for the need to consider treatment volume has become clouded by the lack of clarity and a misinterpretation of some early clinical findings. In particular, there is a need to separate our understanding of biologically iso-effective radiation responses from the clinical concept of normal tissue tolerance, as they relate to changes in treatment volume. Animal data, including those for large animals, are reviewed. These animal studies indicate the need for caution in extrapolating retrospective clinical data to new treatment situations, since the conclusions reached may have been dictated by dogma and not by careful consideration of different factors that may have been involved. These include anatomical and physiological factors, and variations in the dose distribution pattern to a specific organ or tissue. These biological factors could limit the general applicability of simple approaches based on mathematical models to the volume effect relationship in radiotherapy.