Evaluating growth failure with diffusion tensor imaging in pediatric survivors of high-risk neuroblastoma treated with high-dose cis-retinoic acid.

Abstract

The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure. To assess physeal abnormalities in children with high-risk neuroblastoma in comparison to normal controls by using diffusion tensor imaging (DTI) of the distal femoral physis and adjacent metaphysis. We prospectively obtained physeal DTI at 3.0T in 20 subjects (mean age: 12.4years, 7 females) with high-risk neuroblastoma treated with high-dose cis-retinoic acid, and 20 age- and gender-matched controls. We compared fractional anisotropy (FA), normalized tract volume (cm3/cm2) and tract concentration (tracts/cm2) between the groups, in relation to height Z-score and response to growth hormone therapy. Tractography images were evaluated qualitatively. DTI parameters were significantly lower in high-risk neuroblastoma survivors compared to controls (P<0.01), particularly if the patients were exposed to both cis-retinoic acid and total body irradiation (P<0.05). For survivors and controls, DTI values were respectively [mean ± standard deviation]: tract concentration (tracts/cm2), 23.2±14.7 and 36.7±10.5; normalized tract volume (cm3/cm2), 0.44±0.27 and 0.70±0.21, and FA, 0.22±0.05 and 0.26±0.02. High-risk neuroblastoma survivors responding to growth hormone compared to non-responders had higher FA (0.25±0.04 and 0.18±0.03, respectively, P=0.02), and tract concentration (tracts/cm2) (31.4±13.7 and 14.8±7.9, respectively, P<0.05). FA, normalized tract volume and tract concentration were linearly related to height Z-score (R2>0.31; P<0.001). Qualitatively, tracts were nearly absent in all non-responders to growth hormone and abundant in all responders (P=0.02). DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.