Radio-prevention of micrometastases

In developed countries, the cancer incidence is about 150 000 cases per yea r and half of people with cancer may die from the extension of the primary tumour in secondary deposits. This disaster costs more than 2 billion euro per year. People with cancer are often treated with surgery and/or radiothe rapy of localized primary tumour and chemo-prevention of occult disseminate d micrometastases. Since chemotherapy essentially targets cycling tumour ce lls, quiescent micrometastases which may contain only one cell may escape. We previously reported that human melanoma clones with high metastatic pote ntial and low gangliosides content appeared very radiosensitive to low-dose ionizing radiation both in culture and in immunosuppressed animals. This e xquisite radiosensitivity was observed with the highly metastatic single ce lls which were resting at the time of irradiation. These data are consisten t with the dose-response relationship for the radiotherapy of secondary dep osits which appears linear with no threshold. Highly metastatic cells at an early stage of growth also appear very sensitive to chemicals and activate d immune cells. We propose the medical hypothesis according to which the sp read of resting micrometastases should be prevented by a single fraction of total-body irradiation delivered at a dose sufficiently low (below 0.2 Gy) to avoid normal tissue radiotoxicity. Radio-prevention may complement stan dard treatments for patients with metastases and may be delivered even for patients in whom no distant metastases were detected on tumour diagnosis (M O stage). (C) 2001 Harcourt Publishers Ltd.