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Neutron radiobiology and clinical consequences.

The present day rationale for anticipating a therapeutic advantage of neutrons over X-rays is reviewed. It is based on the following characteristics of tumorous tissue: hypoxia, poor cell cycle redistribution, large repair capacity and rapid growth. It is obvious that not all of the possible reasons why X-ray therapy may fail can be circumvented by the use of neutrons. Therefore the practical consequences of the mentioned rationales must be the planning of randomized clinical trials. With patients selected for poorly reoxygenating tumors, tumors in which clonogens proliferate slowly and others where they grow rapidly and/or show an early regenerative response. Predictive assays for such a selection are, however, only scarcely available and need to be developed to supplement the indication given by conventional staging and grading. Other important consequences of radiobiological considerations are finally concerning treatment strategies. Regardless of the exact dose per fraction chosen, it seems prudent to use relatively low doses per fraction initially to maximize the chance of detecting any benefit inherent in the use of neutrons, before exploring increased doses for reasons of improved cost-effectiveness.