Biological Effect of Single, Very Large Dose Fractions as Used in Intraoperative Radiotherapy (IORT)

Abstract

Intraoperative radiotherapy differs from conventional fractionated radiotherapy by giving a large dose in a single fraction. Various studies suggest that biological effects of dose fractions larger than 5-10 Gy may be different from those induced by conventional fraction sizes. Here, we classify the clinical dose response for different patterns of tumor cells left after surgery. Isoeffective doses of single fractions estimated from fractionated radiotherapy by using the linear-quadratic formalism are consistent with clinical experience from tumor control after radiosurgery. Using a model cell line in vitro, we show that the DNA repair response induced by 6-18 Gy differs from that after 0-2 Gy suggesting saturation of the repair machinery. Possible influences of the tumor microenvironment that may contribute to making very large dose fractions more effective than predicted from clonogenic cell inactivation alone are reviewed.