Failure of hyperfractionated radiotherapy to reduce bone growth arrest in rats

Abstract Purpose : Radiotherapy of the craniospinal axis is causing an age dependent growth arrest in children. The purpose of this paper was to examine in an animal model, whether hyperfractionated radiotherapy, given with twice daily fractions in conventional overall treatment time, would cause less growth arrest of the spinal column than a regular treatment schedule. Methods and Materials : The time-dose-fraction schedule for the treatment of the craniospinal axis of children with medulloblastomas was used as model for the treatment of the spine in rats. The entire spine of weanling rats received either 3570 cGy in 21 daily fractions of the 170 cGy, 5 times per week over 27 days, or 3630 cGy in 33 fractions of 110 cGy, given twice daily with 6-hr intervals over 21 days. Results : Both fraction schedules were isoeffective and caused a growth inhibition of 9.5%. The growth arrest was complete after 1870–2420 cGy. The alpha/beta ratio for the growing rat vertebrae was 3400 cGy. This result contrasts with the growth sparing effect observed with hyperfractionation of accelerated treatment schedules. Conclusion : Growing bone is a fast proliferating tissue. Hyperfractionation with 110 cGy BID compared to 170 cGy given once a day, has no sparing effect on bone growth in rats if given in conventional overall treatment time.