The Power of Radiation Biophysics—Let's Use It

Abstract

Two recent editorials in this Journal about the linear quadratic (LQ) model (1, 2) have debated its use on essentially empirical grounds. Missing are its roots in biophysics and what they state about how it can (and cannot) be used. In the 1970s, 2 roads led to analysis of in vitro cell killing by ionizing radiation in terms of the underlying mechanisms. Kellerer and Rossi (3) explored the statistics of energy deposition in small volumesdthe microdosimetric approach. Chadwick and Leenhouts (4) related cell killing to lesions in 2-stranded DNAdthe biophysical approach. Both approaches postulate that radiation can kill cells by 2 distinct processes, a 1-hit mechanism and another that requires 2 independent events. We began to use the LQ equation in 1973 for the pragmatic reason that it fits the survival data better than the other models we tested (5). It soon emerged that, if key factors were controlled, this equation offers insights into the mechanisms involved in cell death and survival during and after irradiation. Here, we reviewed 4 forms of this equation that describe cell survival in specific circumstances and how they might help those working to improve radiotherapeutic protocols. The basic LQ equation states that the cell surviving fraction (S) is the product of 2 Poisson escape probabilities. The mean numbers of events for the underlying mechanisms are proportional to the first and second powers of dose, D, respectively.