VOLUME EFFECTS IN THE IRRADIATED CANINE SPINAL-CORD - DO THEY EXIST WHEN THE PROBABILITY OF INJURY IS LOW

Purpose: The purpose of this study was to investigate volume effects i n the irradiated canine spinal cord. Materials and methods: Eighty-nin e beagle dogs were given 44-84 Gy photons in 4 Gy fractions to 4 or 20 cm lengths of thoracic spinal cord. As controls, 36 dogs were given 6 0-84 Gy in 2 Gy fractions to a 20 cm length of spinal cord and six dog s were unirradiated. Dogs were evaluated for clinical signs, and after euthanasia, for occurrence of gross lesions, severe lesions of massiv e hemorrhage, white matter necrosis and/or parenchymal atrophy and mil d lesions of focal fiber loss. White matter vacuoles, meningeal thickn ess and dorsal root ganglia lesions were quantified. Data were analyze d to test for an effect of volume on dose-response curves. Results: Si gnificant volume effects were found between 4 and 20 cm lengths of irr adiated spinal cord for gross lesions, severe lesions and mild lesions (8.3-15.0 Gy difference at the ED50 level). The ED50 in 4 Gy fraction s for severe lesions was 56.9 Gy (95% CI 53.1-60.6) for 20 cm and 68.8 Gy (95% CI 64.5-75.1) for 4 cm fields. Significant improvements in th e fit of data to dose-response curves resulted when using models with either parallel or non-parallel curves, but in either case an apprecia ble difference existed between curves at low probabilities of injury. Volume effects were present for meningeal thickness and slopes of dose -response curves were different. Clinical signs correlated well with s evere lesions for 20 cm (ED5O = 54.0 Gy), but not for 4 cm fields (ED5 0 = 77.6 Gy). Conclusions: Volume effects exist for the occurrence of pathologic lesions in irradiated canine spinal cord. Clinical compensa tion for pathologic lesions occur at small, but not large irradiated v olumes. There is insufficient data to support a decreased slope of dos e-response curves with decreased volume. Volume effects estimated at t he 50% level of spinal cord injury could also hold at low probabilitie s of injury characteristic of the clinic. (C) 1998 Elsevier Science Ir eland Ltd.