# A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: Approach

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Igor Shuryak, Jun 28, 2015 Available from:- [Show abstract] [Hide abstract]

**ABSTRACT:**The paper presents a computational stochastic model of virtual cells irradiation, based on Quasi-Markov Chain Monte Carlo method and using biophysical input. The model is based on a stochastic tree of probabilities for each cell of the entire colony. Biophysics of the cells is described by probabilities and probability distributions provided as the input. The adaptation of nucleation and catastrophe theories, well known in physics, yields sigmoidal relationships for carcinogenic risk as a function of the irradiation. Adaptive response and bystander effect, incorporated into the model, improves its application. The results show that behavior of virtual cells can be successfully modeled, e.g. cancer transformation, creation of mutations, radioadaptation or radiotherapy. The used methodology makes the model universal and practical for simulations of general processes. Potential biophysical curves and relationships are also widely discussed in the paper. However, the presented theoretical model does not describe the real cells and tissues. Also the exposure geometry (e.g., uniform or non-uniform exposure), type of radiation (e.g., X-rays, gamma rays, neutrons, heavy ions, etc.) as well as microdosimetry are not presently addressed. The model is focused mainly on creation of general and maximal wide mathematical description of irradiated hypothetical cells treated as complex physical systems. - [Show abstract] [Hide abstract]

**ABSTRACT:**Although the survival rate of cancer patients has significantly increased due to advances in anti-cancer therapeutics, one of the major side effects of these therapies, particularly radiotherapy, is the potential manifestation of radiation-induced secondary malignancies. In this work, a novel evolutionary stochastic model is introduced that couples short-term formalism (during radiotherapy) and long-term formalism (post treatment). This framework is used to estimate the risks of second cancer as a function of spontaneous background and radiation-induced mutation rates of normal and pre-malignant cells. By fitting the model to available clinical data for spontaneous background risk together with data of Hodgkins lymphoma survivors (for various organs), the second cancer mutation rate is estimated. The model predicts a significant increase in mutation rate for some cancer types, which may be a sign of genomic instability. Finally, it is shown that the model results are in agreement with the measured results for excess relative risk (ERR) as a function of exposure age, and that the model predicts a negative correlation of ERR with increase in attained age. This novel approach can be used to analyze several radiotherapy protocols in current clinical practice, and to forecast the second cancer risks over time for individual patients.Biophysik 10/2014; DOI:10.1007/s00411-014-0576-z · 1.58 Impact Factor - Biophysik 08/2011; 50(4). DOI:10.1007/s00411-011-0378-5 · 1.58 Impact Factor