The Radiobiology of Small Fraction Numbers
David J Brenner, Columbia University Medical Center, New York, NYTH-A-BRB-1 Thursday 8:00:00 AM - 9:55:00 AM Room: Ballroom B
There is much interest in reducing fraction numbers in radiotherapy, both in the context of single-fraction radiosurgery, and also for hypofractionation - for example for prostate, lung and breast. We will discuss what radiobiology can tell us about the use and optimization of these new approaches in radiotherapy.
From 1900 to the 1920s radiotherapeutic practice was dominated by the German Erlangen school, which advocated the use of a single large “castrating” dose, as well as pioneering the “crossfire” technique to spare normal tissue - the two keystones of modern stereotactic radiotherapy. By the 1930s, the classic studies of Regaud and Coutard resulted in widespread use of larger fraction numbers, and this has remained the state of the art in most radiotherapeutic settings. We will review the key biological factors that determine radiotherapeutic response, and discuss their application to single-fraction radiosurgery - for malignant tumors, for benign tumors, and for vascular lesions. We conclude that, unless the target lesion is very large, vascular lesions and benign tumors can be well treated with a single dose fraction. For malignant tumors, however, fractionated radiotherapy should always result in a better outcome than a single fraction, particular from the perspective of inactivating hypoxic tumor cells, present in almost all tumors.
Hypofractionation, typically using 5 to 10 rather than 30 to 35 fractions, is becoming increasingly popular for treating some malignant tumors. In the context of the same radiobiology discussed earlier, we will discuss the rationale for hypofractionation for prostate, for breast, and for lung. We conclude that there is a strong biological rationale for hypofractionation of prostate cancer, relating to the paucity of dividing cells in most prostate tumors, which makes them respond to changes in fractionation very much like surrounding normal tissue. In other sites, one might expect hypofractionation to be a possible option for malignancies which are a) low grade, and b) small, and in a parallel-type organ. Hypofractionation of small, low-grade lung / breast tumors meet some of these criteria, and may well be at least non-inferior to more conventional fractionation regimes.
1. Understand the radiobiological principles underlying responses to changes in fractionation
2. Understand their application to single-fraction radiosurgery
3. Understand their application to hypofractionation