Journal of Neuro-Oncology

, Volume 75, Issue 3, pp 301–307 | Cite as

Considerations on the Role of Chemotherapy and Modern Radiotherapy in the Treatment of Childhood Low Grade Glioma

  • Giorgio Perilongo
Childhood Brain Tumors


The treatment of childhood low grade glioma (LGG), if not amenable to complete resection, quite often is a relevant clinical challenge. LGG in many instances are indeed slow growing tumors, which, if not controlled, can cause severe morbidity and ultimately jeopardize life. Most of the time children bearing an unresectable LGG can be considered affected by a chronic disease, deserving protracted cures. The treatment philosophy, which has dictated the treatment of malignant cancers, has also inspired the therapeutic concepts for managing childhood LGG. However, it is getting more and more evident that different strategies are needed for them. LGG represent a highly heterogeneous group of neoplasm and comprehensive treatment concepts rarely meet the individual patient’s needs. After more than 20 years of clinical research it can be stated with confidence that for unresectable, progressive LGG, chemotherapy (CT) represents an effective treatment modality. It delays tumor growth and postpones the use of radiotherapy (RT), thus sparing the deleterious effects of irradiation on a developing brain. However, CT rarely cures LGG and definitively obviates the need of RT or aggressive surgery. Furthermore, little is known on the actual impact of CT on patients’ overall health status. Recent progresses in RT delivering techniques, which allow reducing the safety margins, are tempering the concerns related to the use of this treatment modality in children. This manuscript reviews and expands these data, trying to combine them in a coherent picture that it is hoped can help in directing future research in this field.


chemotherapy hypothalamic glioma low grade glioma optic glioma pilocytic astrocytoma radiotherapy 


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  1. 1.
    Rosenstock, JG, Evans, AE, Schut, L 1976Response to vincristine of recurrent brain tumors in childrenJ Neurosurg45135140PubMedGoogle Scholar
  2. 2.
    Rosenstock, JG, Packer, RJ, Bilaniuk, L, Bruce, DA, Radcliffe, JL, Savino, P 1985Chiasmatic optic glioma treated with chemotherapy. A preliminary reportJ Neurosurg63862866PubMedGoogle Scholar
  3. 3.
    Friedman, HS, Krischer, JP, Burger, P, Oakes, WJ, Hockenberger, B, Weiner, MD, Falletta, JM, Norris, D, Ragab, AH, Mahoney, DH,Jr,  et al. 1992Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a pediatric oncology group randomized phase II studyJ Clin Oncol10249256PubMedGoogle Scholar
  4. 4.
    Moghrabi, A, Friedman, HS, Burger, PC, Tien, R, Oakes, WJ 1993Carboplatin treatment of progressive optic pathway gliomas to delay radiotherapyJ Neurosurg79223227PubMedGoogle Scholar
  5. 5.
    Aquino, VM, Fort, DW, Kamen, BA 1999Carboplatin for the treatment of children with newly diagnosed optic chiasm gliomas: a phase II studyJ Neuro-Oncol41255259CrossRefGoogle Scholar
  6. 6.
    Gururangan, S, Cavazos, CM, Ashley, D, Herndon, JE,2nd, Bruggers, CS, Moghrabi, A, Scarcella, DL, Watral, M, Tourt-Uhlig, S, Reardon, D, Friedman, HS 2002Phase II study of carboplatin in children with progressive low grade gliomasJ Clin Oncol2029512958CrossRefPubMedGoogle Scholar
  7. 7.
    McCowage, G, Tien, R, McLendon, R, Felsberg, G, Fuchs, H, Graham, ML, Kurtzberg, J, Moghrabi, A, Ferrell, L, Kerby, T, Duncan-Brown, M, Stewart, E, Robertson, PL, Colvin, OM, Golembe, B, Bigner, DD, Friedman, HS 1996Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose cyclophosphamideMed Pediatr Oncol273239CrossRefPubMedGoogle Scholar
  8. 8.
    Longee, DC, Friedman, HS, Albright, RE, Burger, PC, Oakes, WJ, Moore, JO, Schold, SC 1990Treatment of patients with recurrent gliomas with cyclophosphamide and vincristineJ Neurosurg72583588PubMedGoogle Scholar
  9. 9.
    Kadota, RP, Kun, LE, Langston, JW, Burger, PC, Cohen, ME, Mahoney, DH, Walter, AW, Rodman, JH, Parent, A, Buckley, E, Kepner, JL, Friedman, HS 1999Cyclophosphamide for the treatment of progressive low grade-astrocytoma: a pediatric oncology group phase II studyJ Pediatr Hematol Oncol21198202CrossRefPubMedGoogle Scholar
  10. 10.
    Heideman, RL, Douglass, EC, Langston, JA, Krischer, JP, Burger, PC, Kovnar, EH, Kun, LE, Friedman, HS, Kadota, R 1995A phase II study of every other day high-dose ifosfamide in pediatric brain tumors: a pediatric oncology group studyJ Neuro-oncol257784CrossRefGoogle Scholar
  11. 11.
    Reddy, AT, Packer, JP 1999Chemotherapy for low grade gliomaChild Nerv Syst15506513CrossRefGoogle Scholar
  12. 12.
    Mulne, AF, Ducore, JM, Elterman, RD, Friedman, HS, Krischer, JP, Kun, LE, Shuster, JJ, Kadota, RP 2000Oral methotrexate for recurrent brain tumors in children: a pediatric oncology group studyJ Pediatr Hematol Oncol224144CrossRefPubMedGoogle Scholar
  13. 13.
    Blaney, SM, Philipps, PC, Packer, RJ, Heideman, RL, Berg, SL, Adamson, PC, Allen, JC, Sallan, SE, Jakacki, RJ, Lange, JB, Reaman, GH, Horowitz, ME, Poplack, DG, Balis, FM 1996Phase II evaluation of topotecan for pediatric central nervous system tumorsCancer78527531CrossRefPubMedGoogle Scholar
  14. 14.
    Kadota, RP, Stewart, CF, Horn, M, Kuttesch, JF,Jr, Burger, PC, Kepner, J, Kun, LE, Friedman, HS, Heideman, RL 1999Topotecan for the treatment of progressive central nervous system tumors – a pediatric oncology group phase II studyJ Neuro-oncol434347CrossRefGoogle Scholar
  15. 15.
    Chamberlain, MC, Grafe, MR 1995Recurrent chiasmatic-hypothalamic glioma treated with oral etoposideJ Clin Oncol1320722076PubMedGoogle Scholar
  16. 16.
    Chamberlain, MC 1997Recurrent cerebellar gliomas: salvage therapy with oral etoposideJ Child Neurol12200204PubMedGoogle Scholar
  17. 17.
    Packer, RJ, Sutton, LN, Bilaniuk, LT, Radcliffe, J, Rosenstock, JG, Siegel, KR, Bunin, GR, Savino, PJ, Bruce, DA, Schut, L 1988Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an updateAnn Neurol237985CrossRefPubMedGoogle Scholar
  18. 18.
    Packer, RJ, Lange, B, Ater, J, Nicholson, J, Allen, J, Walker, R, Prados, M, Jakacki, R, Reaman, GR, Needles, MN, Phillips, PC, Ryan, J, Boyett, JM, Geyer, R, Finlay, J 1993Carboplatin and vincristine for progressive low grade gliomas of childhoodJ Clin Oncol11850857PubMedGoogle Scholar
  19. 19.
    Packer, RJ, Ater, J, Allen, J, Phillips, P, Geyer, R, Nicholson, HS, Jakacki, R, Kurczynski, E, Needle, M, Finlay, J, Reaman, G, Boyett, JM 1997Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low grade gliomasJ Neurosurg86747754PubMedGoogle Scholar
  20. 20.
    Castello, MA, Schiavetti, A, Padula, A, Varrasso, G, Properzi, E, Trasimeni, G, Operamolla, P, Gualdi, GF, Clerico, A 1995Does chemotherapy have a role in low grade glioma management?Med Pediatr Oncol25102108PubMedGoogle Scholar
  21. 21.
    Bouffet, E, Amat, D, Devaux, Y, Desuzinges, C 1997Chemotherapy for spinal cord astrocytomaMed Pediatr Oncol29560562CrossRefPubMedGoogle Scholar
  22. 22.
    Massimino, M, Spreafico, F, Cefalo, G,  et al. 2002High response rate to cisplatin/etoposide regimen in childhood low-grade gliomaJ Clin Oncol2042094216CrossRefPubMedGoogle Scholar
  23. 23.
    Pons, MA, Finlay, JL, Walker, RW, Puccetti, D, Packer, RJ, McElwain, M 1992Chemotherapy with vincristine and etoposide in children with low grade astrocytomaJ Neuro-oncol14151158CrossRefGoogle Scholar
  24. 24.
    Walter, AW, Gajjar, A, Reardon, DA, Thompson, SJ, Langston, JW, Jones-Wallace, D, Kun, LE, Heideman, RL 2000Tamoxifen and carboplatin for children with low-grade gliomas: a pilot study at St Jude Children’s Research HospitalJ Pediatr Hematol Oncol3247251Google Scholar
  25. 25.
    Petronio, J, Edwards, MSB, Prados, M, Freyberger, S, Rabbitt, J, Silver, P, Levin, VA 1991Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapyJ Neurosurg74701708PubMedGoogle Scholar
  26. 26.
    Prados, MD, Edwards, MSB, Rabbitt, J, Lamborn, K, Davis, RL, Levin, VA 1997Treatment of pediatric low grade gliomas with a nitrosourea-based multiagent chemotherapy regimenJ Neuro-oncol32235241CrossRefGoogle Scholar
  27. 27.
    Laithier, V, Grill, J, Deley, MC, Ruchoux, MM, Couanet, D, Doz, F, Pichon, F, Rubie, H, Frappaz, D, Vannier, JP, Babin-Boilletot, A, Sariban, E, Chastagner, P, Zerah, M, Raquin, MA, Hartmann, O, Kalifa, C 2003French Society of Pediatric Oncology: progression-free survival in children with optic pathway tumours: dependence on age and the quality of the response to chemotherapy – results of the first french prospective study for the French Society of Pediatric OncologyJ Clin Oncol2145724578CrossRefPubMedGoogle Scholar
  28. 28.
    Gnekow AK, Packer RJ, Kortmann RD: Astrocytic tumors, low grade: treatment consideration by primary site and tumor dissemination. In: Walker DPerilongo GPunt JAG, Taylor RE (eds) Arnold publisher, London, pp. 259–276Google Scholar
  29. 29.
    Janss, AJ, Grundy, R, Cnaan, A, Savina, PJ, Packer, RJ, Zackai, EH, Goldwein, JW, Sutton, LN, Radcliffe, J, Molloy, PT, Phillips, PC, Lange, BJ 1995Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-upCancer7510511059PubMedGoogle Scholar
  30. 30.
    Fouladi, M, Hunt, DL, Pollack, IF, Dueckers, G, Burger, PC, Becker, LE, Yates, AJ, Gilles, FH, Davis, RL, Boyett, JM, Finlay, JL 2003Outcome 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-945Cancer9812431252CrossRefPubMedGoogle Scholar
  31. 31.
    Fouladi, M, Wallace, D, Langston, JW, Mulhern, R, Rose, SR, Gajjar, A, Sanford, RA, Merchant, TE, Jenkins, JJ, Kun, LE, Heideman, RL 2003Survival and functional outcome of children with hypothalamic/chiasmatic tumorsCancer9710841092CrossRefPubMedGoogle Scholar
  32. 32.
    Gajjar, A, Sanford, RA, Heideman, R, Jenkins, JJ, Walter, A, Li, Y, Langston, JW, Muhlbauer, M, Boyett, JM, Kun, LE 1997Low grade astrocytoma: a decade of experience at St. Jude Children’s Research HospitalJ Clin Oncol1527922799PubMedGoogle Scholar
  33. 33.
    Chan, MY, Foong, AP, Heisey, DM, Harkness, W, Hayward, R, Michalki, A 1998Potential prognostic factors of relapse-free survival in childhood optic pathway glioma: a multivariate analysisPediatr Neurosurg292329CrossRefPubMedGoogle Scholar
  34. 34.
    Komotar, RJ, Burger, PC, Carson, BS, Brem, H, Olivi, A, Goldthwaite, PT, Tihan, T 2004Pilocytic and pilomyxoid hypothalamic /chiasmatic astrocytomasNeurosurgery547280PubMedGoogle Scholar
  35. 35.
    Bowers, DC, Gargan, L, Kapur, P, Reisch, JS, Mulne, AF, Shapiro, KN, Elterman, RD, Winick, NJ, Margraf, LR 2003Labeling index as a predictor of tumor progression in plocytic astrocytomas in children and adolescentsJ Clin Oncol2129682973CrossRefPubMedGoogle Scholar
  36. 36.
    Sutton, LN, Molloy, PT, Sernyak, H, Goldwein, J, Phillips, PL, Rorke, LB, Moshang, T,Jr, Lange, B, Packer, RJ 1995Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgeryJ Neurosurg83583589PubMedGoogle Scholar
  37. 37.
    Gropman, AL, Packer, RJ, Nicholson, HS, Vezina, LG, Jakacki, R, Geyer, R, Olson, JM, Phillips, P, Needle, M, Broxson, EH,Jr, Reaman, G, Finlay, J 1998Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term controlCancer83166172CrossRefPubMedGoogle Scholar
  38. 38.
    Lacaze, E, Kieffer, V, Street, A, Lorenzi, C, Gentaz, E, Habrand, JL, Dellatolas, G, Kalifa, C, Grill, J 2003Neuropsychological outcome in children with optic pathway tumours when first line treatment is chemotherapyBr J Cancer8920382044CrossRefPubMedGoogle Scholar
  39. 39.
    Kiebert, GM, Curran, D, Aaronson, NK, Bolla, M, Menten, J, Rutten, EH, Nordman, E, Silvestre, ME, Pierart, M, Karim, AB 1998Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised phase III trial on dose response (EORTC trial 22844). EORTC radiotherapy co-operative groupEur J Cancer3419021909CrossRefPubMedGoogle Scholar
  40. 40.
    Kortmann, RD, Timmermann, B, Taylor, RE, Scarzello, G, Plasswill, P, Paulsen, F, Jeremic, B, Gnekow, AK, Diechmann, K, Kay, S, Bamberg, G 2003Current and future strategies in radiotherapy of childhood low grade glioma of the brain Part I: treatment modalities of radiotherapyStrahlenther Onkol179509520PubMedGoogle Scholar
  41. 41.
    Nishihori, T, Shirato, H, Aoyama, H, Onimaru, R, Komae, T, Ishii, N, Ikeda, J, Miyasaka, K, Sawamura, Y, Iwasaki, Y 2002Three-dimensional conformal radiotherapy for astrocytic tumors involving the eloquent area in children and young adultsJ Neuro-oncol60177183CrossRefGoogle Scholar
  42. 42.
    Merchant, TE, Zhu, Y, Thompson, SJ, Sontag, MR, Heideman, RL, Kun, LE 2002Preliminary results from a phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymomaInt J Radiat Oncol Biol Phys52325332CrossRefPubMedGoogle Scholar
  43. 43.
    Saran, FH, Baumert, BG, Khoo, VS, Adams, EJ, Garre, ML, Warrington, AP, Brada, M 2002Stereotactically guided conformal radiotherapy for progressive low-grade gliomas of childhoodInt J Radiat Oncol Biol Phys534351CrossRefPubMedGoogle Scholar
  44. 44.
    Hug, EB, Muenter, MW, Archambeau, JO, DeVries, A, Liwnicz, B, Loredo, LN, Grove, RI, Slater, JD 2002Conformal proton radiation therapy for pediatric low-grade astrocytomasStrahlenther Onkol1781017CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Neuro-oncology Program, Division of Haematology-Oncology, Department of PediatricsUniversity Hospital of PaduaPaduaItaly

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