Beyond the linear quadratic model: Intraoperative radiotherapy and normal tissue tolerance

Objective: In recent years increasing number of patients are treated with intraoperative, high dose-low energy radiotherapy. The purpose of this review is to evaluate whether the linear-quadratic model (L-Q model) is appropriate for predictive modeling and relative biological effectiveness (RBE) calculations of this new radiation. Methods: All pertinent literature addressing radiobiological aspects of L-Q formulism on high dose-high energy hypofractions [including one fraction intraoperative radiotherapy (IORT)] and high dose-low energy radiation was reviewed and analyzed with regard to clinical utility. Results: Due to the lack of inclusion and experimental verification of a significant number of factors, biological (i.e., no SLD repair, no cell repopulation between fractions, no reoxygenation, long delivery time and steeper dose fall off which affects RBE)/physiological and systemic (i.e., effects on immune systems), which impact on the effectiveness of high dose-low energy radiation, would make the L-Q model inappropriate for predictive modeling of normal tissue complications. Conclusions: L-Q model is inappropriate to model biological effect of either high dose-high energy or high dose-low energy radiation.