Modeling progression in radiation-induced lung adenocarcinomas |
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Authors: | Hatim Fakir Werner Hofmann Rainer K Sachs |
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Institution: | (1) London Regional Cancer Program, 790 Commissioners Rd. E., London, ON, N6A 4L6, Canada;(2) Department of Mathematics, University of California, Berkeley, CA, USA;(3) Division of Physics and Biophysics, Department of Materials Engineering and Physics, University of Salzburg, Salzburg, Austria |
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Abstract: | Quantitative multistage carcinogenesis models are used in radiobiology to estimate cancer risks and latency periods (time
from exposure to clinical cancer). Steps such as initiation, promotion and transformation have been modeled in detail. However,
progression, a later step during which malignant cells can develop into clinical symptomatic cancer, has often been approximated
simply as a fixed lag time. This approach discounts important stochastic mechanisms in progression and evidence on the high
prevalence of dormant tumors. Modeling progression more accurately is therefore important for risk assessment. Unlike models
of earlier steps, progression models can readily utilize not only experimental and epidemiological data but also clinical
data such as the results of modern screening and imaging. Here, a stochastic progression model is presented. We describe,
with minimal parameterization: the initial growth or extinction of a malignant clone after formation of a malignant cell;
the likely dormancy caused, for example, by nutrient and oxygen deprivation; and possible escape from dormancy resulting in
a clinical cancer. It is shown, using cohort simulations with parameters appropriate for lung adenocarcinomas, that incorporating
such processes can dramatically lengthen predicted latency periods. Such long latency periods together with data on timing
of radiation-induced cancers suggest that radiation may influence progression itself. |
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