Fractionation in radiotherapy

Abstract

Soon after the discovery of X-rays by Conrad Rijntgen in 1895, clinicians started experiments with the use of X-ray therapy for malignant tumors. In these early days two schools emerged, each promoting a different treatment approach. The first and most influential school until 1920 promoted the delivery of a large, single dose. The biological justification was the assumption that recovery from radiation injury was more efficient in rapidly growing tumor cells than in normal tissues and the fear that a fractionated dose might cause normal tissue injury because of accumulation of radiation damage. The second school used fractionated treatments using multiple low-dose-rate fractions. It was assumed that fractionation would increase the chance that tumor cells were irradiated in the more sensitive mitotic phase. The first experimental demonstration of the therapeutic benefit of fractionation came from the work of Regaud and Ferroux in 1927. They showed that with fractionated irradiation of the scrotum it was possible to sterilize a ram with less skin damage than after a single dose. In 1929, Coutard achieved the first cures of deep-seated tumors, mainly in the head and neck, using fractionated low-dose-rate regimens that were individually adapted depending on the patients skin and mucosal reaction. His workwas responsible for the definitive breakthrough of fractionated radiotherapy. Based on economic grounds, however, many centers had to discontinue the original Coutard’s low-dose-rate fractionation method in favour of fractionated high-dose-rate treatment. Baclesse, who succeeded Coutard at the lnstitut Curie, demonstrated that the fraction size rather than the dose rate had the greatest influence on the intensity of acute skin reactions. He also showed that severe skin and mucosal reactions could be avoided by extending the overall treatment time. It is the Baclesse method that forms the basis of what is presently called ‘conventional’ fractionation. The work of Strandqvist published in 1944 (54) was important in the establishment of the relationship between dose and time in the development of acute radiation reactions. During the following years it became apparent that time-dose-fractionation parameters of acutely responding tissues differed from those of latereacting tissues. This led to the development of a number of isoeffect formulae for various types of tissues. The most widely used mathematical model to describe the