Lack of influence of sequence of top-up doses on repair kinetics in rat spinal cord.

BACKGROUND AND PURPOSE

The rat spinal cord model was used to determine whether repair kinetics changed during a course of fractionated radiotherapy if twice daily doses were given either at the initial or final period of a concomitant boost irradiation schedule.

MATERIALS AND METHODS

The rat cervical spinal cord was irradiated from C2-T2 in 870 animals with top-up doses of three daily fractions of 9 Gy representing 75% of the biologic dose at the ED50 level for white matter necrosis. To simulate concomitant boost protocols, these top-up doses were given either preceding (initial top-up) or following (final top-up) a b.i.d. schedule of 1 Gy/F delivered at 0, 1, 2, 4, 8 or 24 h interfraction intervals. The end point was forelimb paralysis secondary to white matter necrosis.

RESULTS

For interfraction intervals of 0, 1, 2, 4, 8 and 24 h, the initial top-up schedules yielded ED50 values of 18.2, 19.2, 23.7, 21.3, 27.2 and 29.7 Gy, respectively; the corresponding ED50s from the final top-up schedules were 17.5, 19.0, 20.7, 21.2, 26.9 and 30.3 Gy, respectively. A 10% reduction in the ED50 value from pooled data was observed when the interfraction interval was reduced from 24 (ED50 = 30.3 Gy) to 8 h (ED50 = 27.1 Gy). Fitting the incomplete repair (IR) version of the LQ model with mono-exponential repair kinetics gave alpha/beta values of 1.4 and 1.5 Gy, and similar repair half-times of 4.3 and 5.0 h for the initial and final top-up experiments, respectively. The IR model with bi-exponential repair kinetics did not provide a better fit to the data.

CONCLUSIONS

We conclude that the sequence of top-up doses has no apparent influence on radiation sensitivity or repair kinetics in the rat spinal cord. The clinical implication is that the interfraction interval but not the timing of the boost is a critical determinant of spinal cord tolerance in concomitant boost protocols.