Investigation of the effect of natural tumor cell death on radiotherapy outcomes. (9th October 2018)

• Record Type: Journal Article
• Authors: Stavrev, Pavel; Stavreva, Nadejda; Penev, Dimitar; Nahum, Alan; Ruggieri, Ruggero; Pressyanov, Dobromir
• Is Part Of: Physics in medicine & biology. Volume 63:Number 20(2018:Oct.)
• Publication Date: 2018-10-09
• Subjects: tumor control probability (TCP) -- cell death -- Monte-Carlo -- data analysis; Biophysics -- Periodicals; Medical physics -- Periodicals; 610.153
• DOI: 10.1088/1361-6560/aae05d
• Languages: English
• ISSNs: 0031-9155

Abstract

Abstract: The aim of the work is to investigate the impact of radiation-independent (natural or spontaneous) tumor cell death on tumor control probability (TCP) during and following fractionated external-beam radiotherapy employing both analytical and numerical methods. The analytical method solves a TCP model accounting for tumor repopulation and non-radiation tumor cell death during fractionated external-beam radiotherapy. The numerical method is based on a Monte Carlo simulation of the processes of radiation-induced cell kill, as well as cell division and natural cell death randomly taking place in the time interval between fractions. Distributions of the number of surviving cells are constructed using the Monte Carlo method for cases with and without natural cell death. The analytically and numerically calculated values of TCP were found to be in excellent agreement (as shown in the Method and materials section), thereby validating both methods. The TCP model is then fitted to two different experimental data sets with the aim of determining the model parameter values, primarily the natural death rate. Two versions of the linear-quadratic model of cell damage—with and without assumed re-sensitization of the tumor cells during treatment—are used. In two of the fits a strong correlation between the repopulation and spontaneous cell death rates is observed. It was possible to determine separately the values of the two rates only in the fit of the model with resensitization to the most diversified data set consisting of seven different fractionation regimes. The observed correlation together with a theoretical consideration leads to the conclusion that in most cases it is the net effect of the two processes of birth and death rather than the processes separately that determines treatment outcome. However, depending on the values of the rates of the two processes and the duration of the treatment, the treatment outcome may be more accurately determined by the absolute values of the two rates rather than just by their difference.