Large-dose fractionation (hypofractionation)

Abstract

Fractionation is a radiotherapeutic "modality" that may be manipulated to attempt to improve control of malignant tumors or to decrease effects on normal tissues. In addition, some fractionation regimen must be selected as the basis for addition of any other modality such as radiosensitizers or hyperthermia. Considerable literature derived from clinical experiences with reduced numbers of large fractions has become available in the last 15 years. A review of this literature is focused on tumor control and effects on normal tissues resulting from hypofractionation (fewer than five fractions/week), rapid fractionation (large daily fractions treated five times/week), and rapid split-course regimens that include a rest interval in the course of treatment. The evidence available indicates that a decrease in tumor control is associated with each of these large-dose fractionation approaches. At the same time, late effects on normal tissues are increased as the result of the large-sized fractions. The overall reduction in therapeutic ratio suggests that this avenue of clinical research should no longer be pursued and that such regimens should be adopted with caution for purposes of combining radiosensitizers or hyperthermia. Conversely, clinical research in radiotherapy justifiably can explore the effects of increased numbers of small fractions.