The kinetics of tumour cell proliferation and radiotherapy

The radiosensitivity of a cell varies throughout the cell cycle, and the effects of a course of radiotherapy depend therefore on the distribution of the proliferating cells into the various phases of the cell cycle and on the proportion and characteristics of the quiescent cells. This is true not only of the first dose of radiation, but also applies when the subsequent doses are delivered. The difference in cell cycle durations between normal and malignant tissues and between different experimental and human tumour types is relatively small. It cannot be evoked to explain the wide range of tumour doubling times, which seems largely to be due to differences in the proportions of proliferating cells (growth fraction) and rates of cell loss. The slowing down of the growth rate of a solid tumour depends on these two parameters. In solid tumours, these parameters may vary from the centre of the tumour to its periphery and appear to be influenced by environmental factors. At least four types of factors can influence the growth rate of a tumour: immune reactions against tumour cells, metabolic conditions, cell crowding and specific inhibitors or stimulators. Various types of quiescent non-cycling cells may exhibit differences in radiosensitivity and repair capacity after sublethal damage. Irradiation or cytotoxic drugs produce a disturbance of the kinetics of tumour cell proliferation. An acceleration of the growth rate of surviving tumour cells has been observed both in man and in the experimental animal. This may be due either to depopulation which in itself increases the availability of nutrients or to the liberation of growth stimulating substances by necrotic cells. This repopulating ability of some tumours during a fractionated course of radiotherapy may be a reason for local failure. A better understanding of this phenomenon may help in the choice of the optimum type of fractionation.