Low-Grade Glioma in Children: Effects of Radiotherapy

  • Erin S. Murphy
  • Thomas E. Merchant
Part of the Pediatric Cancer book series (PECA, volume 3)


Low-grade gliomas are a heterogeneous group of tumors that overall have a better prognosis than WHO grade III and IV tumors. However, these tumors can devastate a child because of progression in proximity to critical structures, or the long-term consequences of therapy. Observation after complete surgical resection is standard of care. Tumors may demonstrate an indolent natural history after incomplete resection, but progression-free survival at 5 years is only 56%. The choice of treatment remains controversial, particularly for younger children because of the anticipated adverse effects of therapy including neurocognitive dysfunction, endocrinopathy, hearing loss, vasculopathy, and malignant transformation. Advances in radiotherapy and thoughtful planning techniques seek to minimize these long-term sequelae and maintain a good quality of life for children with low-grade gliomas.


Growth Hormone Deficiency Precocious Puberty Optic Pathway Glioma Optic Glioma Subependymal Giant Cell Astrocytoma 
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. Alvord EC Jr, Lofton S (1988) Gliomas of the optic nerve or chiasm: outcome by patients’ age, tumor site, and treatment. J Neurosurg 68(1):85–98PubMedCrossRefGoogle Scholar
  2. Bloom HJ, Glees J, Bell J, Ashley SE, Gorman C (1990) The treatment and long-term prognosis of children with intracranial tumors: a study of 610 cases, 1950–1981. Int J Radiat Oncol Biol Phys 18(4):723–745PubMedCrossRefGoogle Scholar
  3. Brauner R, Malandry F, Rappaport R, Zucker JM, Kalifa C, Pierre-Kahn A, Bataini P, Dufier JL (1990) Growth and endocrine disorders in optic glioma. Eur J Pediatr 149(12):825–828PubMedCrossRefGoogle Scholar
  4. Broniscer A, Baker SJ, West AN, Fraser MM, Proko E, Kocak M, Dalton J, Zambetti GP, Ellison DW, Kun LE, Gajjar A, Gilbertson RJ, Fuller CE (2007) Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. J Clin Oncol 25(6):682–689PubMedCrossRefGoogle Scholar
  5. Chadderton RD, West CG, Schuller S, Quirke DC, Gattamaneni R, Taylor R (1995) Radiotherapy in the treatment of low-grade astrocytomas. II. The physical and cognitive sequelae. Childs Nerv Syst 11(8):443–448PubMedCrossRefGoogle Scholar
  6. Collet-Solberg PF, Sernyak H, Satin-Smith M, Katz LL, Sutton L, Molloy P, Moshang T Jr (1997) Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma. Clin Endocrinol (Oxf) 47(1):79–85CrossRefGoogle Scholar
  7. Douw L, Klein M, Fagel SS, van den Heuvel J, Taphoorn MJ, Aaronson NK, Postma TJ, Vandertop WP, Mooij JJ, Boerman RH, Beute GN, Sluimer JD, Slotman BJ, Reijneveld JC, Heimans JJ (2009) Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 8(9):810–818PubMedCrossRefGoogle Scholar
  8. Fisher BJ, Leighton CC, Vujovic O, Macdonald DR, Stitt L (2001) Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys 51(3):704–710PubMedCrossRefGoogle Scholar
  9. Fouladi M, Hunt DL, Pollack IF, Dueckers G, Burger PC, Becker LE, Yates AJ, Gilles FH, Davis RL, Boyett JM, Finlay JL (2003) Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children’s Cancer Group high-grade glioma study CCG-945. Cancer 98(6):1243–1252PubMedCrossRefGoogle Scholar
  10. Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE (1997) Low-grade astrocytoma: a decade of experience at St. Jude Children’s Research Hospital. J Clin Oncol 15(8):2792–2799PubMedGoogle Scholar
  11. Gnekow AK, Kortmann RD, Pietsch T, Emser A (2004) Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy – report from the multicenter treatment study for children and adolescents with a low grade glioma – HIT-LGG 1996 – of the Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr 216(6):331–342PubMedCrossRefGoogle Scholar
  12. Grill J, Couanet D, Cappelli C, Habrand JL, Rodriguez D, Sainte-Rose C, Kalifa C (1999) Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol 45(3):393–396PubMedCrossRefGoogle Scholar
  13. Janss AJ, Grundy R, Cnaan A, Savino PJ, Packer RJ, Zackai EH, Goldwein JW, Sutton LN, Radcliffe J, Molloy PT (1995) Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up. Cancer 75(4):1051–1059PubMedCrossRefGoogle Scholar
  14. Jenkin D, Angyalfi S, Becker L, Berry M, Buncic R, Chan H, Doherty M, Drake J, Greenberg M, Hendrick B et al (1993) Optic glioma in children: surveillance, resection, or irradiation? Int J Radiat Oncol Biol Phys 25(2):215–225PubMedCrossRefGoogle Scholar
  15. Kidd EA, Mansur DB, Leonard JR, Michalski JM, Simpson JR, Perry A (2006) The efficacy of radiation therapy in the management of grade I astrocytomas. J Neurooncol 76(1):55–58PubMedCrossRefGoogle Scholar
  16. Klein M, Heimans JJ, Aaronson NK, van der Ploeg HM, Grit J, Muller M, Postma TJ, Mooij JJ, Boerman RH, Beute GN, Ossenkoppele GJ, van Imhoff GW, Dekker AW, Jolles J, Slotman BJ, Struikmans H, Taphoorn MJ (2002) Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet 360(9343):1361–1368PubMedCrossRefGoogle Scholar
  17. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCentralPubMedCrossRefGoogle Scholar
  18. Marcus KJ, Goumnerova L, Billett AL, Lavally B, Scott RM, Bishop K, Xu R, Young Poussaint T, Kieran M, Kooy H, Pomeroy SL, Tarbell NJ (2005) Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys 61(2):374–379PubMedCrossRefGoogle Scholar
  19. Massimino M, Spreafico F, Riva D, Biassoni V, Poggi G, Solero C, Gandola L, Genitori L, Modena P, Simonetti F, Potepan P, Casanova M, Meazza C, Clerici CA, Catania S, Sardi I, Giangaspero F (2010) A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neurooncol 100(1):65–71PubMedCrossRefGoogle Scholar
  20. Mehrkens JH, Kreth FW, Muacevic A, Ostertag CB (2004) Long term course of WHO grade II astrocytomas of the Insula of Reil after I-125 interstitial irradiation. J Neurol 251(12):1455–1464PubMedCrossRefGoogle Scholar
  21. Merchant TE, Hua CH, Shukla H, Ying X, Nill S, Oelfke U (2008) Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 51(1):110–117PubMedCrossRefGoogle Scholar
  22. Merchant TE, Conklin HM, Wu S, Lustig RH, Xiong X (2009a) Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits. J Clin Oncol 27(22):3691–3697PubMedCrossRefGoogle Scholar
  23. Merchant TE, Kun LE, Wu S, Xiong X, Sanford RA, Boop FA (2009b) Phase II trial of conformal radiation therapy for pediatric low-grade glioma. J Clin Oncol 27(22):3598–3604PubMedCrossRefGoogle Scholar
  24. Mishra KK, Puri DR, Missett BT, Lamborn KR, Prados MD, Berger MS, Banerjee A, Gupta N, Wara WM, Haas-Kogan DA (2006) The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas. Neuro Oncol 8(2):166–174PubMedCentralPubMedCrossRefGoogle Scholar
  25. Mishra KK, Squire S, Lamborn K, Banerjee A, Gupta N, Wara WM, Prados MD, Berger MS, Haas-Kogan DA (2010) Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update. J Neurooncol 100(1):121–127PubMedCentralPubMedCrossRefGoogle Scholar
  26. Packer RJ, Sutton LN, Bilaniuk LT, Radcliffe J, Rosenstock JG, Siegel KR, Bunin GR, Savino PJ, Bruce DA, Schut L (1988) Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol 23(1):79–85PubMedCrossRefGoogle Scholar
  27. Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, Jakacki R, Kurczynski E, Needle M, Finlay J, Reaman G, Boyett JM (1997) Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 86(5):747–754PubMedCrossRefGoogle Scholar
  28. Pollack IF, Claassen D, al-Shboul Q, Janosky JE, Deutsch M (1995) Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg 82(4):536–547PubMedCrossRefGoogle Scholar
  29. Shaw EG, Daumas-Duport C, Scheithauer BW, Gilbertson DT, O’Fallon JR, Earle JD, Laws ER Jr, Okazaki H (1989) Radiation therapy in the management of low-grade supratentorial astrocytomas. J Neurosurg 70(6):853–861PubMedCrossRefGoogle Scholar
  30. Stander M, Peraud A, Leroch B, Kreth FW (2004) Prognostic impact of TP53 mutation status for adult patients with supratentorial World Health Organization Grade II astrocytoma or oligoastrocytoma: a long-term analysis. Cancer 101(5):1028–1035PubMedCrossRefGoogle Scholar
  31. Tao ML, Barnes PD, Billett AL, Leong T, Shrieve DC, Scott RM, Tarbell NJ (1997) Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome. Int J Radiat Oncol Biol Phys 39(3):579–587PubMedCrossRefGoogle Scholar
  32. van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmstrom PO, Collette L, Pierart M, Mirimanoff R, Karim AB (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490):985–990PubMedCrossRefGoogle Scholar
  33. West CG, Gattamaneni R, Blair V (1995) Radiotherapy in the treatment of low-grade astrocytomas. I. A survival analysis. Childs Nerv Syst 11(8):438–442PubMedCrossRefGoogle Scholar
  34. Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE (2011) Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children’s Oncology Group. Neurosurgery 68(6):1548–1554PubMedCrossRefGoogle Scholar
  35. Yule SM, Hide TA, Cranney M, Simpson E, Barrett A (2001) Low grade astrocytomas in the West of Scotland 1987–1996: treatment, outcome, and cognitive functioning. Arch Dis Child 84(1):61–64PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Radiation OncologyTaussig Cancer InstituteClevelandUSA
  2. 2.Division of Radiation OncologySt. Jude Children’s Research HospitalMemphisUSA

Personalised recommendations