Modelling radiation effects in the gastrointestinal epithelium: Applications to radiotherapy scheduling optimisation

A problem presented at the VPH NoE SG Nottingham 2009.

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Presented by:
Prof Alastair Munro (Department of Surgery and Oncology, Ninewells Hospital, University of Dundee)
Dr Ingeborg van Leeuwen (Department of Surgery and Oncology, Ninewells Hospital, University of Dundee)
Participants:
RE Alcantara, JR King, DE Morris, AJ Munro, AJ Narracott, Y Shen, B Stransky, MZ Ullah, IMM van Leeuwen, JP Ward, M Zachariou

Problem Description

Cancer therapy with drugs and/or radiation can damage the structure and functional integrity of the gastrointestinal epithelium, the extent of the damage being dependent upon a number of identifiable variables. Such damage is dose-limiting, while limitations on dose may compromise the effectiveness of treatment. There have been extensive studies on the kinetics of damage and repair of the gastrointestinal epithelium following a variety of insults. Some of these data have already been incorporated into mathematical models.

Assessing dose-limiting bystander effects in the gut epithelium Radiotherapy protocols are generally planned based solely on the tolerance of normal tissues directly exposed to the beam. Recent experimental evidence suggest, however, that cells outside the exposure field are subject to radiation-induced bystander effects, resulting from cell-cell and cell-matrix interactions. The spatial propagation of bystander effects is particularly relevant at low doses, as under these conditions only a small number of cells suffer a “direct hit”. We propose to use mathematical modelling to quantify such DNA-damage-independent effects and estimate the resulting net tolerance of the normal tissue.

Devising optimal treatment schedules for patients with cancer Most schedules currently used in clinical practice have been derived empirically and are employed in a standard fashion, with little account taken of patient-to-patient variation. We suggest that it should be possible, using available biological data in conjunction with mathematical modelling, to devise an approach to treatment scheduling that is more individually based and takes account of patient-to-patient variation in susceptibility to harm. In essence it may be possible to increase the intensity of scheduling for patients who are at lower risk of treatment-related gastrointestinal damage and, conversely, decrease intensity for patients considered to be particularly susceptible to the adverse effects of treatment.

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Study Group Report

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