Studies of dose-fractionation on early and late responses in pig skin: A reappraisal of the importance of the overall treatment time and its effects on radiosensitization and incomplete repair

Randomised multicentre trials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. CHART Steering Committee

“…Completion of all radiotherapy before significant reaction was visible in the skin may have increased tolerance because when compensatory proliferation in the normal skin occurred it could proceed without inhibition by further irradiation. A similar finding has now been reported in the skin of pigs (Hopewell and Van Den Aardweg, 1991). The use of CHART in those patients where the full thickness of skin must be irradiated has given a well-tolerated reaction unlike that normally observed with conventional radiotherapy (Dische, 1992).…”

Changes in the effect of dose fractionation during daily fractionated irradiation: studies in mouse oral mucosa

“…In human skin, Turesson and Thames (19) observed an increase in the ␣/␤ value for acute erythema and desquamation from 7.5-11.2 Gy for overall treatment times Ͻ4 weeks to 18 -34.5 Gy for longer treatment times. In pig skin, ␣/␤ increased from 3.5 Gy for an overall treatment time of 16 days to 35 Gy for 39 days (20). In rat skin, Moulder and Fischer (21) found similar ED50 values for moist desquamation for irradiation with either 10 or 16 fractions within 3 weeks.…”

“…Recently, however, a number of studies have reported changes in recovery capacity after single conditioning doses in mouse oral mucosa (16), mouse skin (17), and rat skin (18). Moreover, data in human epidermis (19), pig skin (20), and rat skin (21) suggest variations in recovery capacity during the overall treatment time of fractionated irradiation.…”

Evidence for Two Forms of Substructure in the Cell Survival Curve: Mechanisms and Clinical Consequences

“…1b and 4 and shows that heterogeneity in radioresponsiveness of mixed cell populations necessarily leads to response substructure (or non-linearity) of the type that we have observed, even when homogeneous subpopulations follow a simple LQ dose-response function. More recent studies by Hopewell et al showed a similar non-linearity in the reciprocal isoeffect curve for the early reaction in pig skin, even when correction was made for possible incomplete repair (32). The a/b ratio at low dose per fraction was approximately 10-fold smaller than at high dose per fraction.…”

“…The a/b ratio at low dose per fraction was approximately 10-fold smaller than at high dose per fraction. Dermal necrosis, a late effect in pig skin (32) and late lung damage (reduced lung function) (33) also indicated a decreased a/b ratio at low dose per fraction. Studies by Wong et al (34,35) of the effects of small doses per fraction on rat spinal cord gave similar results: the value of a/b decreased sharply at low dose per fraction (down to 0.55 Gy/fraction).…”