Late Skeletal Effects in Sheep Treated as Lambs With Targeted vs. Wide Symmetrical Spinal Fields

Abstract

<h3>Purpose/Objective(s)</h3> Craniospinal irradiation (CSI) is a standard treatment for pediatric medulloblastoma. The conventional CSI technique is associated with incidental radiotherapy (RT) to organs at risk (OARs). In growing children, RT can cause subsequent skeletal abnormalities such as curvature and bone growth retardation. However, these effects have not been sufficiently studied for children receiving symmetrical spinal fields. We tested the null hypothesis that narrow spinal fields (NSFs) typical of CSI would cause in 10 degrees increased curvature and 10 cm less spinal growth longitudinally than standard wide spinal fields (WSFs), with lambs as an animal model for children. <h3>Materials/Methods</h3> RT treatment plans were designed for 6 MV photon fields and delivered to lambs of ages 6 weeks or younger—four receiving NSFs that targeted the thecal sac, four receiving wide fields, and four not receiving radiation. Half of the lambs in each set were male and half were female. We chose lambs as a model for children because of their skeletal behavioral resemblance to that of humans. RT fields were expanded laterally with 3 mm margins to produce planning target volumes. RT dose was 27 Gy in 8 fractions, biologically equivalent to the standard total dose of 36 Gy in 20 fractions. Every 6 months and at 2 years, after full growth of lambs in all three arms of the study, thoracic scoliosis Cobb angle, thoracic and lumbar kyphosis Cobb angle, and vertebral hypoplasia in the thoracic spine were measured using computed tomography and compared. <h3>Results</h3> Although differences were observed between the experimental and control (no RT) sets, our hypothesis was found to be false for each spinal abnormality measure. Specifically, between the sheep receiving NSF and WSF, less than 10 degrees increased curvature and 10 cm shorter spinal growth was observed. Mean scoliosis Cobb angles were 0.7, 4.0 and 4.7 degrees for the control, WSF and NSF arms, respectively. Mean thoracic kyphosis Cobb angles were 10.7, 9.0 and 7.0 degrees for the control, WSF and NSF arms, respectively. Mean lumbar kyphosis Cobb angles were 12.3, 7.7 and 9.3 degrees for the control, WSF and NSF arms, respectively. Spinal lengths from occipital bone to sacrum were 78, 70 and 66 cm, for the control, WSF and NSF arms, respectively. <h3>Conclusion</h3> We found no differences in spinal curvature or length in fully-grown sheep between targeted and wide spinal RT characteristic of CSI that had been irradiated as young lambs. This suggests that targeted photon fields may be applied to children receiving CSI, potentially reducing their risks of long-term toxicities, including secondary malignancies. Studies on human subjects are needed to confirm the same findings with children receiving CSI.