Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity.
Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes (alpha/beta of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to < or = 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an alpha/beta of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the alpha/beta value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes > or = 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Radiation Oncology, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Canada.
C S
CS
Wong
Y
Y
Hao
R P
RP
Hill
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005552:Forelimb / Q000528:radiation effects; D007668:Kidney / Q000528:radiation effects; D016014:Linear Models; D016015:Logistic Models; D051379:Mice; D009336:Necrosis; D010243:Paralysis / Q000209:etiology; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology; D011836:Radiation Tolerance; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000528:radiation effects; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors