A 100-year Nordic perspective on the dose-time problem in radiobiology

The therapeutic use of x-rays began almost immediately after their discovery by Röntgen, and within a few years two Swedish physicians could report the first successful treatment of human skin cancer by radiotherapy. Almost from the start it was clear that the biological effect of ionizing radiation depended critically on the exact distribution of the dose in time. The present paper reviews the historical development of dose-time concepts in radiotherapy as seen from a Nordic perspective. Among the topics reviewed are the discussion of single versus fractionated doses, Strandqvist's thesis and the development of power-law biological dose formulas, the effect of dose per fraction and of overall treatment time. It is only within the last 10-15 years that biologically and clinically important dissociation between the radiobiology of early- and late-responding human normal tissues has been appreciated. Biological developments have led to the proposal of altered fractionation schedules, hyperfractionation and accelerated fractionation, that are currently undergoing clinical trial.