Impact of spinal cord repair kinetics on the practice of altered fractionation schedules.
The kinetics of repair of sublethal lesions in the spinal cord was assessed in detail using a rodent model. Experiments were designed to obtain the fractionation sensitivity, alpha/beta, and to quantify the kinetics of repair after a clinically relevant fraction size. Pairs of 2-Gy fractions at intervals ranging from 0 to 24 h were given from Monday through Friday, to cumulative doses of 40-84 Gy. In addition, two groups of animals received 1.5 or 1.2 Gy twice a day at 8-h intervals, 5 days a week, to total doses of 66-90 Gy and 67.2-98.4 Gy, respectively. All irradiations were followed by a top-up dose of 16 Gy. Analysis of the experimental data revealed that a bi-exponential repair model fit the experimental data significantly better than did the mono-exponential model (p = 0.002). The repair half times obtained were 0.7 (0.2-1.3) h and 3.8 (2.6-4.9) h, respectively. The proportion of injury repaired by the longer half time was estimated to be 0.62 (0.37-0.86). The data showed that delivering 2 fractions per day at 6- or 8-h intervals instead of one per day led to a 16.5% (11.8-21.1%) and 13.5% (9.1-17.8%) reduction in the tolerance, respectively. Finally, the results indicated that when incomplete repair between fractions was accounted for, the linear-quadratic (LQ) model was valid in describing fractionation response down to 1.2 Gy per fraction.
Ang
K K
KK
Department of Radiotherapy, U.T.M.D. Anderson Cancer Center, Houston 77030.
Jiang
G L
GL
Guttenberger
R
R
Thames
H D
HD
Stephens
L C
LC
Smith
C D
CD
Feng
Y
Y
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015994:Incidence; D016013:Likelihood Functions; D010243:Paralysis / Q000209:etiology / Q000503:physiopathology; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D011836:Radiation Tolerance; D051381:Rats; D011916:Rats, Inbred F344; D012018:Reflex / Q000528:radiation effects; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013118:Spinal Cord Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D003037:Cobalt Radioisotopes