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The development of predictive tests of normal tissue response to radiation therapy

Objectif

The aim of this concerted action is to bring together the intellectual and technical resources of 14 research groups within Europe to develop methods by which the patients, most at risk, of radiotherapy complications can be identified.

The success of curative radiotherapy depends critically on those patients who are most at risk of dose-limiting complications. At the present time, the standard approach for radiotherapy with curative intent is to prescribe the maximum dose that is judged by the radiotherapist to be within the limit of normal-tissue tolerance. This dose is chosen on the basis of clinical experience to be one that will not lead to serious complications in more than a few percent of cases. This project foreshadows an important change in the strategy of radiation therapy : the individualisation of dose prescription. Tissue and blood specimens will be taken before treatment begins and subjected in the laboratory to a series of tests aimed at achieving the best possible prediction of normal-tissue tolerance to radiation therapy. On the basis of these tests we aim to identify that sub-group of patients who are most at risk of damage. Two principal options will then become available to improve patient management : to reduce the intensity of treatment for the patients who are most at risk of damage, and to increase the intensity of treatment for the majority of patients, thereby increasing their likelihood of achieving local tumour control.

Patients who suffer complications of radiotherapy fall into 3 groups : those who show a severe early reaction to irradiation; those who show a level of late radiation damage that stands out as being excessive; and those who suffer early tissue effects that are so severe that treatment has to be curtailed. The first 2 categories represent patients whose sensitivity to radiation treatment is in the upper part of the normal range. These are the patients whose reactions limit the dose of radiation that can be given. Depending upon the tumour site (and therefore on the normal tissues at risk) they may amount to 2 - 5% of patients given radiotherapy with curative intent. Within Europe they could thus amount to approximately 3,400 to 8,4000 patients per year.

The specific objectives include the following :

- To establish a standardised experimental basis for the inter-comparison of results from the participating laboratories.
- To provide an agreed classification of patients' normal tissue responses to radiotherapy.
- To establish the range of individual cellular radiosensitivity and its relationship to the variation of normal-tissue response to radiatherapy.
- To evaluate and establish the reproducibility and accuracy of rapid assays of cellular radiosensitivity that may be applicable for clinical predictive assays of normal-tissue radiosensitivity.
- To agree methods of clinical evaluation of predictive assays tests of normal-tissue response prior to the introduction of prospective clinical trials.

Determination of the intrinsic radiosensitivity of individual patients is expected to lead to significant improvements in health care. Firstly, it will reduce the serious complications of radiotherapy which are a burden not only to the individual patients but also have significant cost implications for the health-care system. Secondly, it may lead to improved management of the majority of patients by increasing local tumour control.

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CON - Coordination of research actions

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Institute of Cancer Research
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Royaume-Uni

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