Radio-prevention of micrometastases.

ABSTRACT

In developed countries, the cancer incidence is about 150,000 cases per year 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 radiotherapy of localized primary tumour and chemo-prevention of occult disseminated micrometastases. Since chemotherapy essentially targets cycling tumour cells, quiescent micrometastases which may contain only one cell may escape. We previously reported that human melanoma clones with high metastatic potential and low gangliosides content appeared very radiosensitive to low-dose ionizing radiation both in culture and in immunosuppressed animals. This exquisite radiosensitivity was observed with the highly metastatic single cells which were resting at the time of irradiation. These data are consistent with the dose-response relationship for the radiotherapy of secondary deposits which appears linear with no threshold. Highly metastatic cells at an early stage of growth also appear very sensitive to chemicals and activated immune cells. We propose the medical hypothesis according to which the spread 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 standard treatments for patients with metastases and may be delivered even for patients in whom no distant metastases were detected on tumour diagnosis (M0 stage).