A kinetic model of tumor growth and its radiation response with an application to Gamma Knife stereotactic radiosurgery

TL;DR

This paper presents a mathematical kinetic model for tumor growth and radiation response, successfully simulating tumor dynamics in rats and humans after Gamma Knife radiosurgery, and identifying potential predictors of treatment outcome.

Contribution

The study introduces a novel mathematical model incorporating vascular growth and cell clearance, applied to both experimental and clinical data to predict tumor response to radiation therapy.

Findings

Model accurately replicates tumor growth and response in rat and human cases.

Identifies alpha-value and vascular growth retardation factor as potential predictors.

Highlights the need for larger clinical studies to validate predictors.

Abstract

We developed a mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. We made several key assumptions of the model. Tumor volume is composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time, Td) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, theta. Upon irradiation the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time, Tcl. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumor and metastatic brain tumors of five patients who were treated by Gamma Knife stereotactic radiosurgery (GKSRS). By selecting appropriate model parameters, we showed the temporal variation of the tumors for both the rat experiment and the clinical GKSRS cases could be easily replicated by the simple model. Additionally, the application of our model to the GKSRS cases showed that the alpha-value, which is an indicator of radiation sensitivity in the LQ model, and the retardation factor theta could be predictors of the post-treatment volume change. Since there is a large statistical uncertainty of this result due to the small sample size, a future clinical study with a larger number of patients is needed to confirm this finding.