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

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 3.0 T in 20 subjects (mean age: 12.4 years, 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.