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Target-cell hypothesis
In vitro
studies of single mammalian cells growing into colonies demonstrated
gradual loss of colony-forming capacity with an increasing single dose of
ionizing radiation to the cells
Mechanism of radiation damage: direct cell kill and loss of vascular endothelial
cells infarcts / vascular collapse poor organ function
What to do?
Intervene
before
RT seemed the only way
Modify dose-fractionation schedules to exploit differences in the shape
of the target-cell survival curve for tumours and late-responding normal
tissues. Many hyperfractionated randomized controlled trials especially
in H&N were thus conducted in the 1990s