Skip to main content

Advertisement

SpringerLink
Log in

Brain Tumors in Children- Current Therapies and Newer Directions

  • Symposium on Pediatric Oncology : Malignant Solid Tumors
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Brain tumors are the second most common malignancy and the major cause of cancer related mortality in children. Though significant advances in neuroimaging, neurosurgery, radiation therapy and chemotherapy have evolved over the years, overall survival rate remains less than 75%. Malignant gliomas, high risk medulloblastoma with recurrence and infant brain tumors continue to be a major cause of therapeutic frustration. Even today diffuse pontine gliomas are universally fatal. Though tumors like low grade glioma have an overall excellent survival, recurrences and progression in eloquent areas pose therapeutic challenges. As research continues to unravel the biology including key molecules and signaling pathways responsible for the oncogenesis of different childhood brain tumors, novel targeted therapies are profiled. Identification of major targets like the Epidermal Growth factor Receptor (EGFR), Platelet Derived Growth Factor Receptor (PDGFR), Vascular Endothelial Growth factor (VEGF) and key signaling pathways like the MAPK and PI3K/Akt/mTOR has enabled us over the recent years to better understand tumor behavior and design tailored therapy. These efforts have improved overall survival of children with brain tumors. This review article discusses the current status of common brain tumors in children and the newer therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Young J, Percy C, Assire A. Cancer incidence and mortality in the United States 1973–1977. Washington: National Cancer Institute; 1981.

    Google Scholar 

  2. Russel D, Rubinstein L. Pathology of the tumors of the nervous system. 5th ed. Baltimore: Williams & Wilkins; 1989.

    Google Scholar 

  3. Cha S. Neuroimaging in neuro-oncology. Neurotherapeutics. 2009;6:465–77.

    Article  PubMed  CAS  Google Scholar 

  4. Noda SE, El-Jawahri A, Patel D, et al. Molecular advances of brain tumors in radiation oncology. Semin Radiat Oncol. 2009;19:171–8.

    Article  PubMed  Google Scholar 

  5. Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brain stem glioma: two challenges for the pediatric oncologist. Oncologist. 2004;9:197–206.

    Article  PubMed  Google Scholar 

  6. Bredel M, Pollack IF, Hamilton RL, et al. Epidermal growth factor receptor expression and gene amplification in high-grade non-brain stem gliomas of childhood. Clin Cancer Res. 1999;5:1786–92.

    PubMed  CAS  Google Scholar 

  7. Pollack IF, Finkelstein SD, Woods J, et al. Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med. 2002;346:420–7.

    Article  PubMed  CAS  Google Scholar 

  8. Raffel C, Frederick L, O’Fallon JR, et al. Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. Clin Canc Res. 1999;5:4085–90.

    CAS  Google Scholar 

  9. Sposto R, Ertel IJ, Jenkin RD, et al. The effectiveness of chemotherapy for treatment of high grade astrocytoma children: results of a randomized trial. A report from the childrens cancer study group. J Neurooncol. 1989;7:165–77.

    Article  PubMed  CAS  Google Scholar 

  10. Finlay JL, Boyett JM, Yates AJ, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Children’s cancer group. J Clin Oncol. 1995;13:112–23.

    PubMed  CAS  Google Scholar 

  11. MacDonald TJ, Arenson EB, Ater J, et al. Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of children’s cancer group study 9933. Cancer. 2005;104:2862–71.

    Article  PubMed  CAS  Google Scholar 

  12. Cohen KJ, Pollack IF, Zhou T, et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the children’s oncology group. Neuro Oncol. 2011;13:317–23.

    Article  PubMed  CAS  Google Scholar 

  13. Walker DA, Punt JA, Sokal M. Clinical management of brain stem glioma. Arch Dis Child. 1999;80:558–64.

    Article  PubMed  CAS  Google Scholar 

  14. Kaplan AM, Albright AL, Zimmerman RA, et al. Brain stem gliomas in children. A children’s cancer group review of 119 cases. Pediatr Neurosurg. 1996;24:185–92.

    Article  PubMed  CAS  Google Scholar 

  15. Sandri A, Sardi N, Genitori L, et al. Diffuse and focal brain stem tumors in childhood: prognostic factors and surgical outcome. Experience in a single institution. Childs Nervous Syst. 2006;22:1127–35.

    Article  CAS  Google Scholar 

  16. Albright AL, Price RA, Buthkelch AN. Brain stem gliomas of children. Cancer. 1983;52:2313–9.

    Article  PubMed  CAS  Google Scholar 

  17. Sirachainan N, Pakakasama S, Visudithbhan A, et al. Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma. Neuro Oncol. 2008;10:577–82.

    Article  PubMed  CAS  Google Scholar 

  18. Broniscer A, Baker JN, Tagen M, et al. Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol. 2010;28:4762–8.

    Article  PubMed  CAS  Google Scholar 

  19. Gururangan S, Chi SN, Young PT, et al. Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brain stem glioma: A pediatric brain tumor consortium study. J Clin Oncol. 2010;28:3069–75.

    Article  PubMed  CAS  Google Scholar 

  20. Zarghooni M, Bartels U, Lee E, et al. Whole genome profiling of pediatric diffuse pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol. 2010;28:1337–44.

    Article  PubMed  CAS  Google Scholar 

  21. Hall WA, Sherr GT. Convection-enhanced delivery: targeted toxin treatment of malignant glioma. Neurosurg Focus. 2006;20:E10.

    Article  PubMed  Google Scholar 

  22. Chen HJ, Panigrahy A, Dhall G, et al. Apparent diffusion and fractional anisotrophy of diffuse intrinsic brain stem glioma. Am J Neuroradiol. 2010;31:1879–85.

    Article  PubMed  CAS  Google Scholar 

  23. Pollack IF, Claassen D, Al-Shboul Q, et al. Low grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg. 1995;82:536–54.

    Article  PubMed  CAS  Google Scholar 

  24. Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24:1397–408.

    Article  PubMed  Google Scholar 

  25. Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997;5:747–54.

    Google Scholar 

  26. Dougherty MJ, Santi M, Brose MS, et al. Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas. Neuro oncol. 2010;12:621–30.

    Article  PubMed  CAS  Google Scholar 

  27. Warren KE, Goldman S, Pollack IF, et al. Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: pediatric brain tumor consortium study PBTC-018. J Clin Oncol. 2011;29:324–9.

    Article  PubMed  CAS  Google Scholar 

  28. Farwell JR, Dohrmann GJ, Flannery JT. Medulloblastoma in childhood: an epidemiological study. J Neurosurg. 1984;61:657–64.

    Article  PubMed  CAS  Google Scholar 

  29. Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: new biological advances. Lancet Neurol. 2007;6:1073–85.

    Article  PubMed  CAS  Google Scholar 

  30. Northcott PA, Korshunov A, Witt H, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 2011;29:1408–14.

    Article  PubMed  Google Scholar 

  31. Rutkowski S, Cohen B, Finlay J, et al. Medulloblastoma in young children. Pediatr Blood Cancer. 2010;54:635–7.

    Article  PubMed  Google Scholar 

  32. Chi SN, Zimmerman MA, Yao X, et al. Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumors. J Clin Oncol. 2009;27:385–9.

    Article  PubMed  Google Scholar 

  33. Allen JC, Siffert J, Hukin J. Clinical manifestations of childhood ependymoma: a multitude of syndromes. Pediatr Neurosurg. 1998;28:49–55.

    Article  PubMed  CAS  Google Scholar 

  34. Mc Lendon RE, Wiestler OD, Kros JM, et al. Ependymoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavanee WK, eds. WHO classification of tumors of the central nervous system. Lyon: IARC press; 2007. pp. 74–80.

    Google Scholar 

  35. Lehman NL. Central nervous system tumors with ependymal features: a broadened spectrum of primarily ependymal differentiation. J Neuropath Exp Neurol. 2008;67:177–88.

    Article  PubMed  Google Scholar 

  36. Mendrzyk F, Korshunov A, Benner A, et al. Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res. 2006;12:2070–9.

    Article  PubMed  CAS  Google Scholar 

  37. Massimino M, Buttarelli, Antonelli M, et al. Intracranial ependymoma: factors affecting outcome. Future Oncol. 2009;5:207–16.

    Article  PubMed  CAS  Google Scholar 

  38. Healey EA, Barnes PD, Kupsky WJ, et al. The prognostic significance of post-operative residual ependymoma. Neurosurgery. 1991;28:666–72.

    Article  PubMed  CAS  Google Scholar 

  39. Merchant TE, Mulheran RK, Krasin MJ, et al. Preliminary results from a phase II trial of conformaradiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol. 2004;22:3156–62.

    Article  PubMed  Google Scholar 

  40. Kyritsis AP. Management of intracranial germ cell tumors. J Neurooncol. 2010;96:143–9.

    Article  PubMed  Google Scholar 

  41. Echevarria ME, Fangusaro J, Goldman S. Pediatric central nervous germ cell tumors: a review. Oncologist. 2008;13:690–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Soumyadeep Khatua and Rosemary Silva for editing and helping with preparation of the manuscript.

Contributions

SK and TSV conceptualized the article; manuscript was written by SK, ZS, MP, SB and TSV, critically analyzed and finalized by SK.

Conflict of Interest

None.

Role of Funding Source

None.

Author information

Authors and Affiliations

  1. Division of Pediatric Neurooncology, Department of Pediatrics, Children’s Cancer Hospital, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 87, Houston, TX, 77030, USA

    Soumen Khatua, Zsila Sousan Sadighi, Michael L. Pearlman, Sunil Bochare & Tribhawan S. Vats

Authors
  1. Soumen Khatua
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zsila Sousan Sadighi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael L. Pearlman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunil Bochare
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tribhawan S. Vats
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Soumen Khatua.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khatua, S., Sadighi, Z.S., Pearlman, M.L. et al. Brain Tumors in Children- Current Therapies and Newer Directions. Indian J Pediatr 79, 922–927 (2012). https://doi.org/10.1007/s12098-012-0689-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-012-0689-9

Keywords

Search

Navigation