Abstract
Purpose
Most pediatric spinal tumors are low-grade gliomas (LGGs). Characterization of these tumors has been difficult given their heterogeneity and rare incidence. The objective was to characterize such tumors diagnosed at our institution.
Methods
Spinal tumors diagnosed in our pediatric patients between 1984 and 2014 were reviewed retrospectively. Demographics, presentation, pathology, imaging, management, and sequelae were examined.
Results
Forty patients had spinal LGG tumors, 24 (62%) of which were pilocytic astrocytomas. The most common initial presentations were pain (n = 15), partial extremity paralysis (n = 13), and ataxia (n = 11), with the diagnosis frequently delayed by months (median = 5.9 months, range 4 days–6.2 years). Twenty-nine patients had some tumor resection, and 8 required adjuvant therapy with chemotherapy (n = 4) or radiation (n = 4) post-resection. Ten other patients received only biopsy for histologic diagnosis, who were treated with chemotherapy (n = 4) or radiation (n = 5) post biopsy. Tumor progression was noted in 16 patients (2 after gross-total resection; 10, partial resection; and 4, biopsy). During the evaluation period, 3 patients died secondary to tumor progression. BRAF status could have shortened progression-free survival: patients with BRAFV600E mutations (n = 3) all experienced progression within 10 months. Long-term sequelae of the disease/treatment were mostly residual neurologic deficits (paresthesia, paralysis), chemotherapy-induced hearing loss, and scoliosis.
Conclusions
Spinal LGG is a rare entity with significant long-term effects. Although surgery is the most common initial treatment option, more in-depth analysis of molecular biomarkers may improve stratification and prognostication.
Similar content being viewed by others
References
Ostrom QT, Gittleman H, Xu J et al (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 18(suppl_5):v1–v75. https://doi.org/10.1093/neuonc/now207
Qaddoumi I, Sultan I, Gajjar A (2009) Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the surveillance, epidemiology, and end results database. Cancer 115(24):5761–5770. https://doi.org/10.1002/cncr.24663
Ahmed R, Menezes AH, Awe OO et al (2014) Long-term incidence and risk factors for development of spinal deformity following resection of pediatric intramedullary spinal cord tumors. J Neurosurg Pediatr 13(6):613–621. https://doi.org/10.3171/2014.1.PEDS13317
Schneider C, Hidalgo ET, Schmitt-Mechelke T et al (2014) Quality of life after surgical treatment of primary intramedullary spinal cord tumors in children. J Neurosurg Pediatr 13(2):170–177. https://doi.org/10.3171/2013.11.PEDS13346
Arnautovic A, Billups C, Broniscer A et al (2015) Delayed diagnosis of childhood low-grade glioma: causes, consequences, and potential solutions. Childs Nerv Syst 31(7):1067–1077. https://doi.org/10.1007/s00381-015-2670-1
Armstrong GT, Conklin HM, Huang S et al (2011) Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro Oncol 13(2):223–234. https://doi.org/10.1093/neuonc/noq178
Khalil J, Chuanying Z, Qing Z et al (2017) Primary spinal glioma in children: Results from a referral pediatric institution in Shanghai. Cancer Radiother 21(4):261–266. https://doi.org/10.1016/j.canrad.2016.11.005
Merchant TE, Kiehna EN, Thompson SJ et al (2000) Pediatric low-grade and ependymal spinal cord tumors. Pediatr Neurosurg 32(1):30–36. https://doi.org/10.1159/000028894
Broniscer A, Baker SD, Wetmore C et al (2013) Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. Clin Cancer Res 19(11):3050–3058. https://doi.org/10.1158/1078-0432.CCR-13-0306
Bouffet E, Pierre-Kahn A, Marchal JC et al (1998) Prognostic factors in pediatric spinal cord astrocytoma. Cancer 83(11):2391–2399
Hayden Gephart MG, Lober RM, Arrigo RT et al (2012) Trends in the diagnosis and treatment of pediatric primary spinal cord tumors. J Neurosurg Pediatr 10(6):555–559. https://doi.org/10.3171/2012.9.PEDS1272
Kutluk T, Varan A, Kafali C et al (2015) Pediatric intramedullary spinal cord tumors: a single center experience. Eur J Paediatr Neurol 19(1):41–47. https://doi.org/10.1016/j.ejpn.2014.09.007
Constantini S, Houten J, Miller DC et al (1996) Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 85(6):1036–1043. https://doi.org/10.3171/jns.1996.85.6.1036
McAbee JH, Modica J, Thompson CJ et al (2015) Cervicomedullary tumors in children. J Neurosurg Pediatr 16(4):357–366. https://doi.org/10.3171/2015.5.PEDS14638
Nadkarni TD, Rekate HL (1999) Pediatric intramedullary spinal cord tumors. Critical review of the literature. Childs Nerv Syst 15(1):17–28
Reimer R, Onofrio BM (1985) Astrocytomas of the spinal cord in children and adolescents. J Neurosurg 63(5):669–675. https://doi.org/10.3171/jns.1985.63.5.0669
Yang RR, Aibaidula A, Wang WW et al (2018) Pediatric low-grade gliomas can be molecularly stratified for risk. Acta Neuropathol 136(4):641–655. https://doi.org/10.1007/s00401-018-1874-3
Choi GH, Oh JK, Kim TY et al (2012) The clinical features and surgical outcomes of pediatric patients with primary spinal cord tumor. Childs Nerv Syst 28(6):897–904. https://doi.org/10.1007/s00381-012-1718-8
Kothbauer KF (2007) Neurosurgical management of intramedullary spinal cord tumors in children. Pediatr Neurosurg 43(3):222–235. https://doi.org/10.1159/000098835
Lassaletta A, Zapotocky M, Mistry M et al (2017) Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas. J Clin Oncol 35(25):2934–2941. https://doi.org/10.1200/JCO.2016.71.8726
Cruz GR, Dias Oliveira I, Moraes L et al (2014) Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas. J Neurooncol 117(2):235–242. https://doi.org/10.1007/s11060-014-1398-1
Banerjee A, Jakacki RI, Onar-Thomas A et al (2017) A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study. Neuro Oncol 19(8):1135–1144. https://doi.org/10.1093/neuonc/now282
Upadhyaya SA, Robinson GW, Harreld JH et al (2018) Marked functional recovery and imaging response of refractory optic pathway glioma to BRAFV600E inhibitor therapy: a report of two cases. Childs Nerv Syst 34(4):605–610. https://doi.org/10.1007/s00381-018-3739-4
Ater JL, Zhou T, Holmes E et al (2012) Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 30(21):2641–2647. https://doi.org/10.1200/JCO.2011.36.6054
Gajjar A, Sanford RA, Heideman R et al (1997) Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. J Clin Oncol 15(8):2792–2799. https://doi.org/10.1200/JCO.1997.15.8.2792
Wilne S, Collier J, Kennedy C et al (2007) Presentation of childhood CNS tumours: a systematic review and meta-analysis. Lancet Oncol 8(8):685–695. https://doi.org/10.1016/S1470-2045(07)70207-3
Wilne S, Koller K, Collier J et al (2010) The diagnosis of brain tumours in children: a guideline to assist healthcare professionals in the assessment of children who may have a brain tumour. Arch Dis Child 95(7):534–539. https://doi.org/10.1136/adc.2009.162057
Kumandas S, Per H, Gumus H et al (2006) Torticollis secondary to posterior fossa and cervical spinal cord tumors: report of five cases and literature review. Neurosurg Rev 29(4):333–338 (discussion 338). https://doi.org/10.1007/s10143-006-0034-8
Fafara-Les A, Kwiatkowski S, Marynczak L et al (2014) Torticollis as a first sign of posterior fossa and cervical spinal cord tumors in children. Childs Nerv Syst 30(3):425–430. https://doi.org/10.1007/s00381-013-2255-9
Scheinemann K, Bartels U, Huang A et al (2009) Survival and functional outcome of childhood spinal cord low-grade gliomas Clinical article. J Neurosurg Pediatr 4(3):254–261. https://doi.org/10.3171/2009.4.PEDS08411
McCormick PC, Stein BM (1990) Intramedullary tumors in adults. Neurosurg Clin N Am 1(3):609–630
McCormick PC, Torres R, Post KD et al (1990) Intramedullary ependymoma of the spinal cord. J Neurosurg 72(4):523–532. https://doi.org/10.3171/jns.1990.72.4.0523
Acknowledgements
We would like to thank Cherise Guess, PhD, ELS, for scientific editing of the final manuscript, and Laura Patterson, AuD, for help with audiogram interpretation.
Funding
This work was supported, in part, by Cancer Center Support Grant CA21765 from the National Cancer Institute and the American Lebanese Syrian Associated Charities (ALSAC).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors report no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Our institutional review board reviewed and approved this retrospective chart review.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Carey, S.S., Sadighi, Z., Wu, S. et al. Evaluating pediatric spinal low-grade gliomas: a 30-year retrospective analysis. J Neurooncol 145, 519–529 (2019). https://doi.org/10.1007/s11060-019-03319-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-019-03319-4