Advertisement

Journal of Radiation Oncology

, Volume 7, Issue 2, pp 187–193 | Cite as

Musculoskeletal outcomes and the effect of radiation to the vertebral bodies on growth trajectories for long-term survivors of high-risk neuroblastoma

  • Matthew J. Ferris
  • Sibo Tian
  • Jeffrey M. Switchenko
  • Nicholas A. Madden
  • Bree R. Eaton
  • Natia Esiashvili
Original Research
  • 16 Downloads

Abstract

Objective

Here, we report musculoskeletal outcomes and the impact of radiotherapy dose on vertebral body growth for an institutional series of long-term survivors of high-risk neuroblastoma.

Methods

We conducted a retrospective study of 23 patients who were disease-free and at least 36 months from the end of treatment. The patients were initially treated from July 2003 to May 2012. Patient records were reviewed for growth percentiles (obtained at approximately 6-month intervals from onset of treatment to the last follow-up) and musculoskeletal comorbidities. RT plans and most recent surveillance CT scans were reviewed for locations of in-field vertebral bodies and corresponding vertebral growth patterns.

Results

The median follow-up was 7.93 years. The median prescribed radiation dose was 21.6 Gy. Musculoskeletal abnormalities included scoliosis (5 patients), muscular hypoplasia (3), and hypodontia (1). The median growth percentile at treatment onset was 35.5 (range, 4.7–100) versus 10 (0–94.1) at the last follow-up. The median numbers of vertebral bodies encompassed (by at least half of their volume) by the 5-, 10-, 15-, and 20-Gy isodose lines were 7 (mean, 6.78), 7 (6.56), 6 (6.17), and 6 (5.52), respectively. Sixteen patients (70.0%) had in-field abnormalities in vertebral body growth, manifesting as stretches of successive vertebral bodies at the same height, while normally there is a gradual vertebral body height increase progressing caudally down the spinal column.

Conclusions

Musculoskeletal abnormalities, below average height, and stunted in-field vertebral body growth are routine in long-term survivors of high-risk neuroblastoma. Sparing vertebral bodies when feasible may lead to improvement in patient growth trajectories.

Keywords

High-risk neuroblastoma Vertebral body radiation Growth trajectories Musculoskeletal effects Survivor effects 

Abbreviations

NB

Neuroblastoma

RT

Radiotherapy

NWTSG

National Wilms’ Tumor Study Group

IMRT

Intensity-modulated radiotherapy

CT

Computed tomography

CDC

Center for Disease Control and Prevention

PACS

Picture archiving and communication system

GEE

Generalized estimating equation

VMAT

Volumetric-modulated arc therapy

AP/PA

Anterior-posterior/posterior-anterior

3DCRT

3D conformal radiotherapy

Notes

Compliance with ethical standards

Funding

This study was funded in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under the award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. Approval for this retrospective pediatric outcomes study was obtained from our institutional review board.

Informed consent

Statement of informed consent was not applicable since the manuscript does not contain any patient data. Patient identifiers were not included to protect identities.

References

  1. 1.
    Mazloom A, Louis CU, Nuchtern J, Kim E, Russell H, Allen-Rhoades W, Krance R, Paulino AC (2014) Radiation therapy to the primary and postinduction chemotherapy MIBG-avid sites in high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 90:858–862CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Marcus KJ, Shamberger R, Litman H, von Allmen D, Grupp SA, Nancarrow CM, Goldwein J, Grier HE, Diller L (2003) Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants. J Pediatr Hematol Oncol 25:934–940CrossRefPubMedGoogle Scholar
  3. 3.
    Casey DL, Kushner BH, Cheung NK, Modak S, LaQuaglia MP, Wolden SL (2016) Local control with 21-Gy radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 96:393–400CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ferris MJ, Danish H, Switchenko JM, Deng C, George BA, Goldsmith KC, Wasilewski KJ, Cash WT, Khan MK, Eaton BR, Esiashvili N (2017) Favorable local control from consolidative radiation therapy in high-risk neuroblastoma despite gross residual disease, positive margins, or nodal involvement. Int J Radiat Oncol Biol Phys 97:806–812CrossRefPubMedGoogle Scholar
  5. 5.
    De Smet AA, Kuhns LR, Fayos JV, Holt JF (1976) Effects of radiation therapy on growing long bones. AJR Am J Roentgenol 127:935–939CrossRefPubMedGoogle Scholar
  6. 6.
    Gonzalez DG, Breur K (1983) Clinical data from irradiated growing long bones in children. Int J Radiat Oncol Biol Phys 9:841–846CrossRefPubMedGoogle Scholar
  7. 7.
    Makipernaa A, Heikkila JT, Merikanto J, Marttinen E, Siimes MA (1993) Spinal deformity induced by radiotherapy for solid tumours in childhood: a long-term follow up study. Eur J Pediatr 152:197–200CrossRefPubMedGoogle Scholar
  8. 8.
    Mayfield JK, Riseborough EJ, Jaffe N, Nehme ME (1981) Spinal deformity in children treated for neuroblastoma. J Bone Joint Surg Am 63:183–193CrossRefPubMedGoogle Scholar
  9. 9.
    Rate WR, Butler MS, Robertson WW Jr, D’Angio GJ (1991) Late orthopedic effects in children with Wilms’ tumor treated with abdominal irradiation. Med Pediatr Oncol 19:265–268CrossRefPubMedGoogle Scholar
  10. 10.
    Wallace WH, Shalet SM, Morris-Jones PH, Swindell R, Gattamaneni HR (1990) Effect of abdominal irradiation on growth in boys treated for a Wilms’ tumor. Med Pediatr Oncol 18:441–446CrossRefPubMedGoogle Scholar
  11. 11.
    Willman KY, Cox RS, Donaldson SS (1994) Radiation induced height impairment in pediatric Hodgkin’s disease. Int J Radiat Oncol Biol Phys 28:85–92CrossRefPubMedGoogle Scholar
  12. 12.
    Halperin EC, Cox EB (1986) Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967–1984. Int J Radiat Oncol Biol Phys 12:1829–1837CrossRefPubMedGoogle Scholar
  13. 13.
    Ducassou A, Gambart M, Munzer C et al (2015) Long-term side effects of radiotherapy for pediatric localized neuroblastoma: results from clinical trials NB90 and NB94. Strahlenther Onkol 191:604–612CrossRefPubMedGoogle Scholar
  14. 14.
    Paulino AC, Wen BC, Brown CK, Tannous R, Mayr NA, Zhen WK, Weidner GJ, Hussey DH (2000) Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239–1246CrossRefPubMedGoogle Scholar
  15. 15.
    Paulino AC, Fowler BZ (2005) Risk factors for scoliosis in children with neuroblastoma. Int J Radiat Oncol Biol Phys 61:865–869CrossRefPubMedGoogle Scholar
  16. 16.
    Kushner BH, Wolden S, LaQuaglia MP et al (2001) Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery. J Clin Oncol 19:2821–2828CrossRefPubMedGoogle Scholar
  17. 17.
    Hogeboom CJ, Grosser SC, Guthrie KA, Thomas PR, D’Angio GJ, Breslow NE (2001) Stature loss following treatment for Wilms tumor. Med Pediatr Oncol 36:295–304CrossRefPubMedGoogle Scholar
  18. 18.
    Kandula S, Sutter A, Prabhu RS, Jegadeesh N, Esiashvili N (2015) Reassessing dose constraints of organs at risk in children with abdominal neuroblastoma treated with definitive radiation therapy: a correlation with late toxicity. Pediatr Blood Cancer 62:970–975CrossRefPubMedGoogle Scholar
  19. 19.
    Kuczmarski RJ, Ogden CL, Guo SS et al (2000) CDC growth charts for the United States: methods and development. Vital Health Stat 11(2002):1–190Google Scholar
  20. 20.
    Limthongkul W, Karaikovic EE, Savage JW, Markovic A (2010) Volumetric analysis of thoracic and lumbar vertebral bodies. Spine J 10:153–158CrossRefPubMedGoogle Scholar
  21. 21.
    Paulino AC, Mayr NA, Simon JH, Buatti JM (2002) Locoregional control in infants with neuroblastoma: role of radiation therapy and late toxicity. Int J Radiat Oncol Biol Phys 52:1025–1031CrossRefPubMedGoogle Scholar
  22. 22.
    Gatcombe HG, Marcus RB Jr, Katzenstein HM, Tighiouart M, Esiashvili N (2009) Excellent local control from radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 74:1549–1554CrossRefPubMedGoogle Scholar
  23. 23.
    Bradfield SM, Douglas JG, Hawkins DS, Sanders JE, Park JR (2004) Fractionated low-dose radiotherapy after myeloablative stem cell transplantation for local control in patients with high-risk neuroblastoma. Cancer 100:1268–1275CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Matthew J. Ferris
    • 1
    • 2
    • 3
  • Sibo Tian
    • 1
    • 2
  • Jeffrey M. Switchenko
    • 2
    • 4
  • Nicholas A. Madden
    • 1
    • 2
  • Bree R. Eaton
    • 1
    • 2
  • Natia Esiashvili
    • 1
    • 2
  1. 1.Department of Radiation OncologyEmory UniversityAtlantaUSA
  2. 2.Winship Cancer InstituteEmory UniversityAtlantaUSA
  3. 3.The Emory ClinicAtlantaUSA
  4. 4.Department of Biostatistics & BioinformaticsEmory UniversityAtlantaUSA

Personalised recommendations