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Development of methods for rapid analysis of tumour oxygenation to allow treatment stratification

Objective

OBJECTIVE:The objective of the project is to increase the overall success of cancer radiotherapy by selection of patients on the basis of the oxygenation status of their tumours for adjuvant therapies designed to eliminate hypoxic (radioresistant) cells. Specific objectives include:&L1.To establish standard protocols for the inter-comparison of techniques for measuring tissue oxygenation.&L2. To study the feasibility of introducing new technologies for measuring oxygen into the clinic.&L3. To determine the predictive power of different methods for measuring oxygen.&L4. To assess the importance of tumour oxygenation as an underlying mechanism influencing tumour progression and response to treatment.

The aim of this Concerted Action is to bring together the intellectual and technical resources of 17 research groups within Europe to develop methods to identify radiotherapy patients with hypoxic radio resistant tumours. The success of radiotherapy depends on the dose of radiation that can be administered and on the radio sensitivity of the tumour. One of the major factors leading to radio resistant tumours is the presence of significant numbers of poorly oxygenated (hypoxic) cells and tumour hypoxia has been definitively linked to failures of radiotherapy to achieve local tumour control. Reducing tumour hypoxia by adjuvant therapies such as allowing patients to breathe carbogen, transfusing anaemic patients or eliminating hypoxic cells by administering bioreductive drugs should significantly increase the number of patients whose tumours are controlled, but all such additional treatments also carry the risk of increased side effects and normal tissue morbidity. Therefore, selection of patients for adjuvant therapies on the basis of the oxygenation status of their tumours would be highly desirable and would allow prescription of anti-hypoxia therapies to those patients likely to benefit from them while sparing patients with better oxygenated tumours from unnecessary extra treatments and risks. Although several methods of identifying hypoxic tumours have been proposed and in some cases evaluated in cancer patients, routine measurements of tumour oxygenation status 5 are not generally used in clinical practice throughout Europe.

Prospective measurement of 1tumour hypoxia has not been accepted as a diagnostic tool on which to base cancer treatment strategies. It is our intention to develop rapid, reliable methods of measuring tumour oxygenation, which can easily be transferred to health care centres where laboratory facilities are limited at present. Measuring the oxygen status of patients' tumours is expected to lead to significant improvements in health care. Firstly, it will be possible to modify treatment of radiotherapy patients with tumours containing significant numbers of hypoxic cells, by administering adjuvant therapies designed to eliminate these hypoxic cells or to make them more sensitive to radiotherapy. This should improve the proportion of patients in whom local tumour control is achieved with benefits both for the individual patients and also for the health services because of the reduction in patients with recurrent tumours requiring additional health care. A second anticipated benefit will be the improved quality of clinical trials of novel anticancer therapies designed to eliminate the hypoxic component of tumours. At present, such therapies are evaluated without knowledge of the degree of hypoxia in patients' tumours, and therefore the degree to which they could be expected to benefit. Stratification of patients in clinical trials on the basis of the oxygenation status of their tumours will improve evaluation of the results of such trials and help to identify sub-groups of patients who will especially benefit from novel therapies.

Keywords: Predictive testing, tumour hypoxia, radiosensitivity, bioreductive drug.

Coordinator

GRAY LABORATORY CANCER RESEARCH TRUST
Address
Mount Vernon Hospital
HA6 2JR Northwood
United Kingdom