Abstract
Pediatric brainstem gliomas are a heterogeneous group of tumors that arise from either the midbrain, pons, or medulla. These tumors make up between 10 and 20 % of all pediatric central nervous system tumors (Jallo et al. 2004; Gilbertson et al. 2003). In the United States, this means that there are approximately 350 new cases each year (Khatua et al. 2011). The serious symptoms and signs produced by these tumors, which range from isolated specific cranial nerve palsies to quadriparesis, are a consequence of the many important neurologic pathways that originate or pass through the brainstem.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aoki Y, Hashizume R, Ozawa T, Banerjee A, Prados M, James CD et al (2012) An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing. J Neuro-Oncol 108(1):29–35
Barua NU, Lowis SP, Woolley M, O’Sullivan S, Harrison R, Gill SS (2013) Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochir (Wien) 155(8):1459–1465
Bouffet E, Jakacki R, Goldman S et al (2012) Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 30(12):1358–1363
Bradley KA, Zhou T, McNall-Knapp RY, Jakacki RI, Levy AS, Vezina G et al (2013) Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children’s oncology group phase 2 study. Int J Radiat Oncol Biol Phys 85(1):e55–e60
Bredlau AL, Korones DN (2014) Diffuse intrinsic pontine gliomas: treatments and controversies. Adv Cancer Res 121:235–259
Broniscer A, Laningham FH, Sanders RP, Kun LE, Ellison DW, Gajjar A (2008) Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113(3):566–572
Cage TA, Samagh SP, Mueller S et al (2013) Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst 29(8):1313–1319
Caretti V, Hiddingh L, Lagerweij T, Schellen P, Koken PW, Hulleman E et al (2013) WEE1 kinase inhibition enhances the radiation response of diffuse intrinsic pontine gliomas. Mol Cancer Ther 12(2):141–150
Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27:900–910
Children’s Oncology Group, National Cancer Institute. Vorinostat and radiation therapy followed by maintenance therapy with vorinostat in treating younger patients with newly diagnosed pontine glioma. ClinicalTrials.gov identifier NCT01189266. Accessed March 2016.
Cillekens JM, Beliën JA, van der Valk P et al (2000) A histopathological contribution to supratentorial glioma grading, definition of mixed gliomas and recognition of low grade glioma with Rosenthal fibers. J Neuro-Oncol 46(1):23–43
Cohen KJ (2009) Current clinical management of children diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG). In: Joint Meeting of the Pediatric and Oncologic Drugs Advisory Committees, 27 April 2009
Donaldson SS, Laningham F, Fischer PG (2008) Advances towards an understanding of brainstem gliomas. J Clin Oncol 24(8):1266–1272
Epstein FJ, Farmer JP (1993) Brain-stem glioma growth patterns. J Neurosurg 78(3):408–412
Farmer JP, Montes JL, Freeman CR, Meagher-Villemure K, Bond MC, O’Gorman AM (2001) Brainstem gliomas. A 10-year institutional review. Pediatr Neurosurg 34(4):206–214
Finlay JL, Zacharoulis S (2005) The treatment of high grade gliomas and diffuse intrinsic pontine tumors of childhood and adolescence: a historical – and futuristic – perspective. J Neuro-Oncol 75(3):253–266
Frazier JL, Lee J, Thomale UW et al (2009) Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. Journal of neurosurgery. Pediatrics 3(4); 259–269
Freeman CR, Farmer JP (1998) Pediatric brain stem gliomas: a review. International journal of radiation oncology, biology, physics, 40(2): 265–271
Freeman CR, Krischer JP, Sanford RA, Cohen ME, Burger PC, del Carpio R, Halperin EC, Munoz L, Friedman HS, Kun LE (1993) Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 27:197–206
Gilbertson RJ, Hill DA, Hernan R, Kocak M, Geyer R, Olson J et al (2003) ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res 9(10 Pt 1):3620–3624
Grill J, Puget S, Andreiuolo F et al (2012) Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58:489
Guillamo JS, Doz F, Delattre JY (2001) Brain stem gliomas. Curr Opin Neurol 14(6):711–715
Gururangan S, Cavazos CM, Ashley D et al (2002) Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol 20(13):2951–2958
Gururangan S, Fangusaro J, Poussaint TY et al (2014) Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas – a Pediatric Brain Tumor Consortium study. Neuro-Oncology 16(2):310–317
Haas-Kogan DA, Banerjee A, Poussaint TY et al (2011) Phase II trial of tipifarnib and radiation in children with newly diagnosed diffuse intrinsic pontine gliomas. Neuro Oncol 13(3):298–306
Hashizume R, Smirnov I, Liu S et al (2012) Characterization of a diffuse intrinsic pontine glioma cell line: implications for future investigations and treatment. J Neuro-Oncol 110(3):305–313
Hashizume R, Andor N, Ihara Y et al (2014) Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med 20:1394–1396
Jakacki RI, Bouffet E, Adamson PC et al (2011) A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children’s Oncology Group phase 1 consortium study. Neuro-Oncology 13(8):910–915
Jallo GI, Biser Rohrbaugh A, Freed D (2004) Brainstem gliomas. Childs Nerv Syst 20(3):143–153
Jones C, Baker SJ (2014) Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer 14(10):651–661
Kaplan AM, Albright AL, Zimmerman RA et al (1996) Brainstem gliomas in children. A Children’s Cancer Group review of 119 cases. Pediatr Neurosurg 24(4):185–192
Kebudi R, Cakir FB (2013) Management of diffuse pontine gliomas in children: recent developments. Pediatr Drugs 15(5):351–362
Khatua S, Moore KR, Vats TS et al (2011) Diffuse intrinsic pontine glioma – current status and future strategies. Childs Nerv Syst 27:1391–1397
Khaw SL, Coleman LT, Downie PA et al (2007) Temozolomide in pediatric low-grade glioma. Pediatr Blood Cancer 49(6):808–811
Kornreich L, Schwarz M, Karmazyn B, Cohen IJ, Shuper A, Michovitz S et al (2005) Role of MRI in the management of children with diffuse pontine tumors: a study of 15 patients and review of the literature. Pediatr Radiol 35(9):872–879
Korones DN, Kretschmar CS, Freeman CR, Fisher PG, Zhou T, Kepner J (2003) Treatment of children with diffuse intrinsic brain stem glioma with standard dose irradiation and vincristine plus oral VP-16. A Pediatric Oncology Group study. Eighth Annual meeting of Society for Neuro-Oncology, Keystone, Colorado, November 13–16, 2003. Neuro-Oncology 5(4):359
Lazareff JA, Bockhorst KH, Curran J et al (1998) Pediatric low-grade gliomas: prognosis with proton magnetic resonance spectroscopic imaging. Neurosurgery 43(4):809–817; discussion 817
Lewis PW, Müller MM, Koletsky MS et al (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:857
Lonser RR, Warren KE, Butman JA et al (2007) Real-time image-guided direct convective perfusion of intrinsic brain stem lesions. J Neurosurg 107:190–197
Louis DN, Rubio MP, Correa KM, Gusella JF, von Deimling A (1993) Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 52(5):507–515
Mandell LR, Kadota R, Freeman C, Douglass EC, Fontanesi J, Cohen ME et al (1999) There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43(5):959–964
Masoudi A, Elopre M, Amini E et al (2008) Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res 28:2437–2442
Mueller S, Hashizume R, Yang X et al (2014) Targeting Wee1 for the treatment of pediatric high-grade gliomas. Neuro-Oncology 16(3):352–360
Nicholson HS, Kretschmar CS, Krailo M et al (2007) Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 110(7):1542–1550
Packer RJ, Boyett JM, Zimmerman RA et al (1994) Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer 74(6):1827–1834
Paugh BS, Broniscer A, Qu C et al (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29:3999
Pollack IF, Shultz B, Mulvihill JJ (1996) The management of brainstem gliomas in patients with neurofibromatosis 1. Neurology 46(6):1652–1660
Pollack IF, Jakacki RI, Blaney SM et al (2007) Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol 9:145–160
Prados MD, Wara WM, Edwards MSB et al (1995) The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy. Int J Radiat Oncol Biol Phys 32:85–91
Puget S, Philippe C, Bax DA et al (2012) Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLoS ONE 7, e30313
Qi S, Yu L, Li H et al (2014) Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol Lett 7(6):1895–1902
Ramos A, Hilario A, Lagares A et al (2013) Brainstem gliomas. Semin Ultrasound CT MRI 34:104–112
Robertson T, Koszyca B, Gonzales M (2011) Overview and recent advances in neuropathology. Part 1: central nervous system tumours. Pathology 43(2):88–92
Sanghavi SN, Needle MN, Krailo MD, Geyer JR, Ater J, Mehta MP (2003) A phase I study of topotecan as a radiosensitizer for brainstem glioma of childhood: first report of the Children’s Cancer Group-0952. Neuro-Oncology 5(1):8–13
Schindler G, Capper D, Meyer J et al (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121(3):397–405
Schomerus L, Merkenschlager A, Kahn T et al (2007) Spontaneous remission of a diffuse brainstem lesion in a neonate. Pediatr Radiol 37(4):399–402
Ullrich NJ, Raja AI, Irons MB et al (2007) Brainstem lesions in neurofibromatosis type 1. Neurosurgery 61(4):762–766; discussion 766
Walker DA, Punt JA, Sokal M (1999) Clinical management of brain stem glioma. Arch Dis Child 80:558–564
Walker DA, Punt JAG, Sokal M (2004) Brainstem tumors. Arnold, London
Walker DA, Liu J, Kieran M et al (2013) A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro-Oncology 15(4):462–468
Warren K, Bent R, Wolters PL, Prager A, Hanson R, Packer R et al (2012) A phase 2 study of pegylated interferon alpha-2b (PEG-Intron((R))) in children with diffuse intrinsic pontine glioma. Cancer 118(14):3607–3613
Wu G, Broniscer A, McEachron TA et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251
Wu G, Diaz AK, Paugh BS et al (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46(5):444–450
Zaky W, Wellner M, Brown RJ et al (2013) Treatment of children with diffuse intrinsic pontine gliomas with chemoradiotherapy followed by a combination of temozolomide, irinotecan, and bevacizumab. Pediatr Hematol Oncol 30(7):623–632
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing
About this chapter
Cite this chapter
Lin, T.F., Prados, M. (2017). Brainstem Gliomas. In: Gupta, N., Banerjee, A., Haas-Kogan, D. (eds) Pediatric CNS Tumors. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-30789-3_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-30789-3_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-30787-9
Online ISBN: 978-3-319-30789-3
eBook Packages: MedicineMedicine (R0)