A novel analytical population TCP model includes cell density and volume variations: application to canine brain tumor

Abstract

TCP models based on Poisson statistics are characterizing the distribution of the surviving clonogens. It enables the calculation of TCP for individuals. In order to describe clinically observed survival data of patient cohorts it is necessary to extend the model. This is typically done by either incorporating variations of various model parameters, or by using an empirical logistic model. The purpose of this work is the development of an analytical population TCP model by mechanistic extension of the Poisson model.The frequency distribution of GTVs is used to incorporate tumor volume variations into the TCP model. Additionally the tumor cell density variation is incorporated. Both versions of the population TCP model were fitted to clinical data and compared to literature. It was shown that clinically observed brain tumor volumes of dogs undergoing radiotherapy are exponentially distributed. The average GTV size was 3.37 cm$^3$. Fitting the population TCP model including the volume variation LQ and track-event model yielded $\alpha=0.36 ~Gy^{-1}$, $\beta=0.045~Gy^{-2}$, $a=0.9$, $T_D=5.0~d$ and $p = 0.36~Gy^{-1}$, $q=0.48~Gy^{-1}$, $a=0.80$, $T_D = 3.0~d$, respectively. Fitting the population TCP model including both the volume and cell density variation yields $\alpha=0.43~Gy^{-1}$, $\beta=0.0537~Gy^{-2}$, $a=2.0$, $T_D=3.0~d$, $\sigma=2.5$ and $p=0.43~ Gy^{-1}$, $q=0.55~Gy^{-1}$, $a=2.0$, $T_D=2.0~d$, $\sigma=3.0$ respectively. Two sets of radiobiological parameters were obtained which can be used for quantifying the TCP for radiation therapy of dog brain tumors. We established a mechanistic link between the poisson statistics based individual TCP model and the logistic TCP model. This link can be used to determine the radiobiological parameters of patient specific TCP models from published fits of logistic models to cohorts of patients.