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

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Abstract

Background

The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure.

Objective

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.

Materials and methods

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.

Results

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).

Conclusion

DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.

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Acknowledgements

The study was supported by National Institutes of Health grants K07 CA166177 (SMM), St. Baldrick’s Foundation, the Clinical and Translational Science Award, and Translational Research Center (UL1-RR-024134).

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Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

    Jorge Delgado

  2. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Diego Jaramillo

  3. Department of Radiology, Penn State Medical Center, Hershey, PA, USA

    Nancy A. Chauvin

  4. Division of Oncology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA, USA

    Michelle Guo, Mackenzie S. Stratton, Hannah E. Sweeney & Sogol Mostoufi-Moab

  5. Department of Radiology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA, USA

    Christian A. Barrera

  6. Division of Endocrinology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, 2716 South St., 14th Floor, Philadelphia, PA, 19146, USA

    Sogol Mostoufi-Moab

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  1. Jorge Delgado
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  2. Diego Jaramillo
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  3. Nancy A. Chauvin
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  4. Michelle Guo
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  8. Sogol Mostoufi-Moab
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Correspondence to Sogol Mostoufi-Moab.

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Delgado, J., Jaramillo, D., Chauvin, N.A. et al. Evaluating growth failure with diffusion tensor imaging in pediatric survivors of high-risk neuroblastoma treated with high-dose cis-retinoic acid. Pediatr Radiol 49, 1056–1065 (2019). https://doi.org/10.1007/s00247-019-04409-1

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  • DOI: https://doi.org/10.1007/s00247-019-04409-1

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