A Primer on Dose-Response Data Modeling in Radiation Therapy.

An overview of common approaches used to assess a dose response for radiation therapy-associated endpoints is presented, using lung toxicity data sets analyzed as a part of the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic effort as an example. Each component presented (eg, data-driven analysis, dose-response analysis, and calculating uncertainties on model prediction) is addressed using established approaches. Specifically, the maximum likelihood method was used to calculate best parameter values of the commonly used logistic model, the profile-likelihood to calculate confidence intervals on model parameters, and the likelihood ratio to determine whether the observed data fit is statistically significant. The bootstrap method was used to calculate confidence intervals for model predictions. Correlated behavior of model parameters and implication for interpreting dose response are discussed.