The four Rs and accelerated repopulation

Rodney Withers set out in 1975 the four Rs of radiobiology that fractionation exploits: repair of sublethal damage (favouring normal tissue), redistribution of cells through the cell cycle, reoxygenation of hypoxic cells and repopulation of surviving clonogens. In 1988 Withers, Taylor and Maciejewski showed from head and neck cancer series that repopulation accelerates about four weeks into a course, so every extra day costs roughly 0.6 Gy of control, which is why treatment breaks are made up, overall time is kept short and accelerated schedules (DAHANCA 6 and 7, CHART in lung cancer) were tested. Time factors now sit in biologically effective dose calculations for fast-growing tumours.