Brainstem Gliomas

  • Tiffany F. Lin
  • Michael PradosEmail author
Part of the Pediatric Oncology book series (PEDIATRICO)


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.


Epidermal Growth Factor Receptor Pilocytic Astrocytoma Epidermal Growth Factor Receptor Gene Diffuse Intrinsic Pontine Glioma Diffuse Glioma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 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):29–35CrossRefGoogle Scholar
  2. 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):1459–1465CrossRefGoogle Scholar
  3. 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):1358–1363CrossRefPubMedGoogle Scholar
  4. 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–e60CrossRefPubMedGoogle Scholar
  5. Bredlau AL, Korones DN (2014) Diffuse intrinsic pontine gliomas: treatments and controversies. Adv Cancer Res 121:235–259CrossRefPubMedGoogle Scholar
  6. 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):566–572CrossRefPubMedGoogle Scholar
  7. 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):1313–1319CrossRefPubMedGoogle Scholar
  8. 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):141–150CrossRefPubMedGoogle Scholar
  9. 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 27:900–910CrossRefGoogle Scholar
  10. 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. identifier NCT01189266. Accessed March 2016.Google Scholar
  11. 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):23–43CrossRefGoogle Scholar
  12. 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 2009Google Scholar
  13. Donaldson SS, Laningham F, Fischer PG (2008) Advances towards an understanding of brainstem gliomas. J Clin Oncol 24(8):1266–1272CrossRefGoogle Scholar
  14. Epstein FJ, Farmer JP (1993) Brain-stem glioma growth patterns. J Neurosurg 78(3):408–412Google Scholar
  15. 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):206–214CrossRefPubMedGoogle Scholar
  16. 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):253–266CrossRefGoogle Scholar
  17. 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); 259–269Google Scholar
  18. Freeman CR, Farmer JP (1998) Pediatric brain stem gliomas: a review. International journal of radiation oncology, biology, physics, 40(2): 265–271Google Scholar
  19. 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 27:197–206CrossRefPubMedGoogle Scholar
  20. 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):3620–3624PubMedGoogle Scholar
  21. Grill J, Puget S, Andreiuolo F et al (2012) Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58:489CrossRefPubMedGoogle Scholar
  22. Guillamo JS, Doz F, Delattre JY (2001) Brain stem gliomas. Curr Opin Neurol 14(6):711–715CrossRefPubMedGoogle Scholar
  23. 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):2951–2958CrossRefPubMedGoogle Scholar
  24. 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):310–317CrossRefPubMedGoogle Scholar
  25. 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):298–306CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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):305–313CrossRefGoogle Scholar
  27. Hashizume R, Andor N, Ihara Y et al (2014) Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med 20:1394–1396CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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):910–915CrossRefPubMedPubMedCentralGoogle Scholar
  29. Jallo GI, Biser Rohrbaugh A, Freed D (2004) Brainstem gliomas. Childs Nerv Syst 20(3):143–153CrossRefPubMedGoogle Scholar
  30. Jones C, Baker SJ (2014) Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer 14(10):651–661Google Scholar
  31. 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):185–192CrossRefPubMedGoogle Scholar
  32. Kebudi R, Cakir FB (2013) Management of diffuse pontine gliomas in children: recent developments. Pediatr Drugs 15(5):351–362CrossRefGoogle Scholar
  33. Khatua S, Moore KR, Vats TS et al (2011) Diffuse intrinsic pontine glioma – current status and future strategies. Childs Nerv Syst 27:1391–1397CrossRefPubMedGoogle Scholar
  34. Khaw SL, Coleman LT, Downie PA et al (2007) Temozolomide in pediatric low-grade glioma. Pediatr Blood Cancer 49(6):808–811CrossRefPubMedGoogle Scholar
  35. 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):872–879CrossRefPubMedGoogle Scholar
  36. 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):359Google Scholar
  37. 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 817CrossRefPubMedGoogle Scholar
  38. 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 340:857CrossRefPubMedPubMedCentralGoogle Scholar
  39. Lonser RR, Warren KE, Butman JA et al (2007) Real-time image-guided direct convective perfusion of intrinsic brain stem lesions. J Neurosurg 107:190–197CrossRefPubMedGoogle Scholar
  40. 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):507–515CrossRefPubMedGoogle Scholar
  41. 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):959–964CrossRefPubMedGoogle Scholar
  42. Masoudi A, Elopre M, Amini E et al (2008) Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res 28:2437–2442PubMedGoogle Scholar
  43. Mueller S, Hashizume R, Yang X et al (2014) Targeting Wee1 for the treatment of pediatric high-grade gliomas. Neuro-Oncology 16(3):352–360CrossRefPubMedGoogle Scholar
  44. 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):1542–1550CrossRefPubMedGoogle Scholar
  45. 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):1827–1834CrossRefPubMedGoogle Scholar
  46. 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 29:3999CrossRefPubMedPubMedCentralGoogle Scholar
  47. Pollack IF, Shultz B, Mulvihill JJ (1996) The management of brainstem gliomas in patients with neurofibromatosis 1. Neurology 46(6):1652–1660CrossRefPubMedGoogle Scholar
  48. 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 9:145–160CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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 32:85–91CrossRefPubMedGoogle Scholar
  50. 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, e30313CrossRefPubMedPubMedCentralGoogle Scholar
  51. 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):1895–1902PubMedPubMedCentralGoogle Scholar
  52. Ramos A, Hilario A, Lagares A et al (2013) Brainstem gliomas. Semin Ultrasound CT MRI 34:104–112CrossRefGoogle Scholar
  53. Robertson T, Koszyca B, Gonzales M (2011) Overview and recent advances in neuropathology. Part 1: central nervous system tumours. Pathology 43(2):88–92CrossRefPubMedGoogle Scholar
  54. 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):8–13PubMedPubMedCentralGoogle Scholar
  55. 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):397–405CrossRefPubMedGoogle Scholar
  56. Schomerus L, Merkenschlager A, Kahn T et al (2007) Spontaneous remission of a diffuse brainstem lesion in a neonate. Pediatr Radiol 37(4):399–402CrossRefPubMedGoogle Scholar
  57. Ullrich NJ, Raja AI, Irons MB et al (2007) Brainstem lesions in neurofibromatosis type 1. Neurosurgery 61(4):762–766; discussion 766CrossRefPubMedGoogle Scholar
  58. Walker DA, Punt JA, Sokal M (1999) Clinical management of brain stem glioma. Arch Dis Child 80:558–564CrossRefPubMedPubMedCentralGoogle Scholar
  59. Walker DA, Punt JAG, Sokal M (2004) Brainstem tumors. Arnold, LondonCrossRefGoogle Scholar
  60. 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):462–468CrossRefPubMedPubMedCentralGoogle Scholar
  61. 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):3607–3613CrossRefPubMedGoogle Scholar
  62. 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 44:251CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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):444–450CrossRefPubMedPubMedCentralGoogle Scholar
  64. 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):623–632CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Division of Hematology/Oncology, Department of PediatricsUniversity of California San Francisco & UCSF Benioff Children’s HospitalSan FranciscoUSA
  2. 2.Departments of Neurological Surgery & PediatricsUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations