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Mathematical modelling of radiotherapy strategies for early breast cancer

Research output: Contribution to journalArticlepeer-review

Author(s)

Heiko Enderling, Alexander R. A. Anderson, Mark A. J. Chaplain, Alastair J. Munro, Jayant S. Vaidya

School/Research organisations

Abstract

Targeted intraoperative radiotherapy (Targit) is a new concept of partial breast irradiation where single fraction radiotherapy is delivered directly to the tumour bed. Apart from logistic advantages, this strategy minimizes the risk of missing the tumour bed and avoids delay between surgery and radiotherapy. It is presently being compared with the standard fractionated external beam radiotherapy (EBRT) in randomized trials. In this paper we present a mathematical model for the growth and invasion of a solid tumour into a domain of tissue (in this case breast tissue), and then a model for surgery and radiation treatment of this tumour. We use the established linear-quadratic (LQ) model to compute the survival probabilities for both tumour cells and irradiated breast tissue and then simulate the effects of conventional EBRT and Targit. True local recurrence of the tumour could arise either from stray tumour cells, or the tumour bed that harbours morphologically normal cells having a predisposition to genetic changes, such as a loss of heterozygosity (LOH) in genes that are crucial for tumourigenesis, e.g. tumour suppressor genes (TSGs). Our mathematical model predicts that the single high dose of radiotherapy delivered by Targit would result in eliminating all these sources of recurrence, whereas the fractionated EBRT would eliminate stray tumour cells, but allow (by virtue of its very schedule) the cells with LOH in TSGs or cell-cycle checkpoint genes to pass on low-dose radiation-induced DNA damage and consequently mutations that may favour the development of a new tumour. The mathematical model presented here is an initial attempt to model a biologically complex phenomenon that has until now received little attention in the literature and provides a ?proof of principle? that it is possible to produce clinically testable hypotheses on the effects of different approaches of radiotherapy for breast cancer.
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Details

Original languageEnglish
Pages (from-to)158-171
Number of pages14
JournalJournal of Theoretical Biology
Volume241
Issue number1
DOIs
Publication statusPublished - Jul 2006

    Research areas

  • Mathematical modelling, Breast cancer, Radiotherapy, Targit, Intraoperative radiotherapy, Targeted intraoperative radiotherapy (Targit)

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