Causes and consequences of inhomogeneous dose distributions in radiation therapy.

Reasons for delivering a non-uniform dose to the target volume are discussed. These include deliberate tailoring of dose to a non-uniform tumor burden or to a non-uniform expectation of the presence of disease, and undesired but unavoidable non-uniformities due to: technical factors; set-up uncertainty; and the need to avoid sensitive organs abutting the target volume. The consequences of non-uniform dose distributions are reviewed and it is suggested that: tumor control may be better characterized by the mean rather than the minimum target absorbed dose when the dose non-uniformity is not too great; modest dose deficits to small sub-volumes of the target volume may not be too deleterious; and modest dose increments to substantial sub-volumes of the target volume may be advantageous. Further modeling, and animal experiments in which tumors are non-uniformly irradiated are required to validate these hypotheses.