The Four R's of Radiotherapy

Radiotherapy given as multiple doses are effective in sterilizing cancers, but the processes whereby the neoplasm is eradicated and the normal tissues are preserved are not fully understood. The differential between normal tissue and tumor response is enhanced by dose fractionation, single doses resulting in severe normal tissue injury when the dose is sufficient to control a proportion of treated tumors. This chapter focuses on the four Rs that influence the outcome of fractionated-dose radiotherapy, one or more of which may account for the relative sparing of normal tissues. These are repair of sublethal injury in normal and neoplastic cells, reoxygenation of the tumor, redistribution through the division cycle, and regeneration of surviving normal and malignant cells between dose fractions. These have been called the four Rs of fractionated radiotherapy. Other factors are involved in the outcome of multifraction radiotherapy—for example, the maintenance of the architectural integrity of the normal tissues, the volume of tissue irradiated, the tumor bed, and the immunocompetence of the host are some other factors that play a significant role in the differential response.