The History and Radiobiology of Hypofractionation

The use of hypofractionation in radiation therapy dates back to the first third of the twentieth century, but was largely abandoned thereafter due to unacceptable normal tissue complications. In recent years however, it has been “repurposed” thanks to more than a century of advances in physics and imaging that now allow most normal tissues to be excluded from the radiation field. Advances in clinical radiobiology—in particular an improved understanding of the differing fractionation sensitivities of normal tissues and tumors—have also contributed to hypofractionation’s return. The biology of hypofractionation is controversial however, not only in terms of hypofractionation’s mechanism(s) of action, but also the appropriateness of using isoeffect models that were developed with conventional and hyperfractionated radiotherapy in mind. The possible roles vascular injury, microimmune effects and volume effects play in hypofractionation’s efficacy remain unclear, so some have questioned the continued use of conventional isoeffect formulae, based largely on the 5Rs of radiotherapy.