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Mathematical modelling of radiotherapy strategies for early breast cancer

Enderling, H; Anderson, ARA; Chaplain, MAJ; Munro, AJ; Vaidya, JS; (2006) Mathematical modelling of radiotherapy strategies for early breast cancer. J THEOR BIOL , 241 (1) 158 - 171. 10.1016/j.jtbi.2005.11.015.

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Abstract

Targeted intraolperative 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. (c) 2005 Elsevier Ltd. All rights reserved.

Type: Article
Title: Mathematical modelling of radiotherapy strategies for early breast cancer
DOI: 10.1016/j.jtbi.2005.11.015
Keywords: mathematical modelling, tumour invasion, breast cancer, radiotherapy, targit, intraoperative radiotherapy, local recurrence, INDUCED GENOMIC INSTABILITY, INTRAOPERATIVE RADIOTHERAPY, CLINICAL-IMPLICATIONS, RANDOMIZED-TRIAL, DOSE-RESPONSE, NORMAL TISSUE, ALLELIC LOSS, RADIATION, HETEROZYGOSITY, IRRADIATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: http://discovery.ucl.ac.uk/id/eprint/170962
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