Non-targeted radiation effects in radiotherapy--roles of radiation-induced genomic instability and of the bystander effect in cancer cure by radiotherapy.

Local tumour control by radiotherapy requires the complete sterilization of all tumour 'stem' cells in the tumour volume. Neither bystander effect nor radiation-induced genomic instability is able to contribute substantially to the probability of local tumour control of the primary cancer by radiotherapy. However, the progeny of these surviving tumour 'stem' cells are likely to suffer from radiation-induced genomic instability, which results in the persistent appearance of non-stem cells, i.e. a reduced probability of self-maintenance. This results in a slower growth rate of the recurrent tumour, a reduced stem-cell fraction and, as a consequence, an increased radiosensitivity of the recurrent tumour. In some recurrent tumours, particularly those that develop very late and grow very slowly, radiosensitivity may be further increased by increased intrinsic radiosensitivity, which could be related to the as yet poorly defined phenotype of 'small colony formation'.