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Second cancers after fractionated radiotherapy : Stochastic population dynamics effects
SACHS Rainer K. ; SHURYAK Igor ; BRENNER David ; ...
When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well-characterized doses of a well-studied carcinogen, followed by long-term monitoring. In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation, can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/ proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze if radiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this IIP model. Combining Monte-Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance»mean, even when pre-malignant clones a
PMID : 17897680 ISSN : 0022-5193 CODEN : JTBIAP
Journal of theoretical biology A. 2007, vol. 249, n° 3, pp. 518-531 [14 pages]
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