Queueing models of potentially lethal damage repair in irradiated cells.

Some of the ideas arising in queueing theory are applied to describe the repair mechanisms responsible for recovery of cells from potentially lethal radiation damage. Two alternative versions are presented of a queueing model of damage repair after a single dose of irradiation. The first version represents a linear misrepair model, and the second invokes the idea of spontaneous lesion fixation. They are pieced together in the third model, allowing for both mechanisms. The consistency of the proposed models with published experimental data is tested.

A distribution of tumor size at detection and its limiting form.

A distribution of tumor size at detection is derived within the framework of a mechanistic model of carcinogenesis with the object of estimating biologically meaningful parameters of tumor latency. Its limiting form appears to be a generalization of the distribution that arises in the length-biased sampling from stationary point processes. The model renders the associated estimation problems tractable. The usefulness of the proposed approach is illustrated with an application to clinical data on premenopausal breast cancer.

A bivariate limiting distribution of tumor latency time.

The model of radiation carcinogenesis, proposed earlier by Klebanov, Rachev, and Yakovlev [8] substantiates the employment of limiting forms of the latent time distribution at high dose values. Such distributions arise within the random minima framework, the two-parameter Weibull distribution being a special case. This model, in its present form, does not allow for carcinogenesis at multiple sites. As shown in the present paper, a natural two-dimensional generalization of the model appears in the form of a Weibull-Marshall-Olkin distribution. Similarly, the study of a randomized version of the model based on the negative binomial minima scheme results in a bivariate Pareto-Marshall-Olkin distribution. In the latter case, an estimate for the rate of convergence to the limiting distribution is given.

A stochastic model of radiation carcinogenesis: latent time distributions and their properties.

A stochastic model of radiation carcinogenesis is proposed that has much in common with the ideas suggested by M. Pike as early as 1966. The model allows us to obtain a parametric family of substochastic-type distributions for the time of tumor latency that provides a description of the rate of tumor development and the number of affected individuals. With this model it is possible to interpret data on tumor incidence in terms of promotion and progression processes. The basic model is developed for a prolonged irradiation at a constant dose rate and includes short-term irradiation as a special case. A limiting form of the latent time distribution for short-term irradiation at high doses is obtained. This distribution arises in the extreme value theory within the random minima framework. An estimate for the rate of convergence to a limiting distribution is given. Based on the proposed latent time distributions, long-term predictions of carcinogenic risk do not call for information about irradiation dose. As shown by computer simulation studies and real data analysis, the parametric estimation of carcinogenic risk appears to be robust to the loss of statistical information caused by the right-hand censoring of time-to-tumor observations. It seems likely that this property, although revealed by means of a purely empirical procedure, may be useful in selecting a model for the practical purpose of risk prediction.

[Theoretical limits to the efficacy of radiotherapy]. / Teoreticheskie granitsy éffektivnosti luchevoi terapii.

The upper bound for expected cancer treatment efficacy expressed as the difference between weighted survival probabilities for normal and neoplastic cells has been obtained. The maximum value of this difference has been recorded in a fixed deviation of distributions of normal and neoplastic cell radiosensitivity.