The role of chemotherapy in the treatment of pediatric brain tumors

Jae-Wook Lee; Nack-Gyun Chung

doi:10.5124/jkma.2012.55.5.420

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Lee and Chung: The role of chemotherapy in the treatment of pediatric brain tumors

Focused Issue of This Month

Pediatric Brain Tumors

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2012; 55(5): 420-429.

Published online: 16 May 2012

DOI: https://doi.org/10.5124/jkma.2012.55.5.420

The role of chemotherapy in the treatment of pediatric brain tumors

Jae-Wook Lee, MD, Nack-Gyun Chung, MD

Department of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Corresponding author: Nack-Gyun Chung, cngped@catholic.ac.kr

Received 2 April 2012 Accepted 16 April 2012

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The past 20 to 30 years have seen significant developments in the diagnosis and treatment of pediatric brain tumors, the most common solid organ tumor in children. Advances have been made in imaging methodologies, such as magnetic resonance imaging, surgical approaches to treatment, classification of brain tumors according to pathological and molecular features, and overall understanding of pertinent prognostic factors. Translation of our knowledge into appropriate therapy for each type of brain tumor has resulted in an overall improved survival. However, subtypes of brain tumor that have actually shown enhanced survival are few, and the overall prognosis for children with brain tumors remains poor compared to that of patients treated for other pediatric malignancies. Recent clinical trials aim to minimize treatment-related toxicity for brain tumors with superior survival, while attempting to improve the cure rate for those tumors with continued poor prognosis through intensified treatment, introduction of novel chemotherapeutic drugs, or targeted treatment based on identified molecular markers. This review outlines the overall role of chemotherapy in the treatment of childhood brain tumors, with an emphasis on recently identified molecular markers and current trends in treatment.

Keywords: Brain neoplasms, Child, Central nervous system, Drug therapy, Targeted therapy

Figures and Tables

Table 1

World Health Organization grades of common pediatric brain tumors

From International Agency for Research on Cancer, et al. WHO classification of tumours of the central nervous system. Lyon: International Agency for Research on Cancer; 2007 [3].

References

1. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, Jemal A, Anderson RN, Ajani UA, Edwards BK. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst. 2011. 103:714–736.

2. Annual report of cancer statistics in Korea [Internet]. Korea Central Cancer Registry. 2002-2008. cited 2012 Apr 30. Goyang: National Cancer Center;Available from: http://ncc.re.kr/manage/manage03_033_list.jsp.

3. Kleihues P, Louis DN, Wiestler OD, Burger PC, Scheithauer BW. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. International Agency for Research on Cancer. WHO grading of tumours of the central nervous system. WHO classification of tumours of the central nervous system. 2007. 4th ed. Lyon: International Agency for Research on Cancer;10–13.

4. Blaney SM, Kun LE, Hunter J, Rorke-Adams LB, Lau C, Strother D, Pollack IF. Pizzo PA, Poplack DG, editors. Tumors of the central nervous system. Principles and practice of pediatric oncology. 2006. 5th ed. Philadelphia: Lippincott Williams and Wilkins;786–864.

5. Dubuc AM, Northcott PA, Mack S, Witt H, Pfister S, Taylor MD. The genetics of pediatric brain tumors. Curr Neurol Neurosci Rep. 2010. 10:215–223.

6. Varan A. Risk-adapted chemotherapy in childhood medulloblastoma. Expert Rev Anticancer Ther. 2011. 11:771–780.

7. Pan E, Pellarin M, Holmes E, Smirnov I, Misra A, Eberhart CG, Burger PC, Biegel JA, Feuerstein BG. Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. Clin Cancer Res. 2005. 11:4733–4740.

8. Pizer B, Clifford S. Medulloblastoma: new insights into biology and treatment. Arch Dis Child Educ Pract Ed. 2008. 93:137–144.

9. Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999. 17:832–845.

10. Kortmann RD, Kuhl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Sorensen N, Warmuth-Metz M, Bamberg M. Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. Int J Radiat Oncol Biol Phys. 2000. 46:269–279.

11. Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Walker DA, Pizer BL, Imeson J, Lashford LS. International Society of Paediatric Oncology. United Kingdom Children's Cancer Study Group. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study. J Clin Oncol. 2003. 21:1581–1591.

12. Tabori U, Sung L, Hukin J, Laperriere N, Crooks B, Carret AS, Silva M, Odame I, Mpofu C, Strother D, Wilson B, Samson Y, Bouffet E. Canadian Pediatric Brain Tumor Consortium. Medulloblastoma in the second decade of life: a specific group with respect to toxicity and management: a Canadian Pediatric Brain Tumor Consortium Study. Cancer. 2005. 103:1874–1880.

13. Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D, Ironside J, Pizer BL, Lashford LS. Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer. 2005. 41:727–734.

14. Jakacki RI, Feldman H, Jamison C, Boaz JC, Luerssen TG, Timmerman R. A pilot study of preirradiation chemotherapy and 1800 cGy craniospinal irradiation in young children with medulloblastoma. Int J Radiat Oncol Biol Phys. 2004. 60:531–536.

15. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005. 352:978–986.

16. Kim SY, Sung KW, Hah JO, Yoo KH, Koo HH, Kang HJ, Park KD, Shin HY, Ahn HS, Im HJ, Seo JJ, Lim YJ, Lee YH, Shin HJ, Lim do H, Cho BK, Ra YS, Choi JU. Reduced-dose craniospinal radiotherapy followed by high-dose chemotherapy and autologous stem cell rescue for children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor. Korean J Hematol. 2010. 45:120–126.

17. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol. 2009. 10:258–266.

18. Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J, Cox T, Chong WK, Campbell RH, Bailey CC, Gattamaneni R, Picton S, Thorpe N, Mallucci C, English MW, Punt JA, Walker DA, Ellison DW, Machin D. Children's Cancer and Leukaemia Group (formerly UKCCSG) Brain Tumour Committee. formerly UKCCSG) Brain Tumour Committee. Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol. 2007. 8:696–705.

19. Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, Broxson E, Donahue B, Finlay JL, Goldwein JW, Heier LA, Johnson D, Mazewski C, Miller DC, Packer R, Puccetti D, Radcliffe J, Tao ML, Shiminski-Maher T. Children's Cancer Group. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol. 2005. 23:7621–7631.

20. Pollack IF, Hamilton RL, James CD, Finkelstein SD, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL. Children's Oncology Group. Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children's Cancer Group 945 cohort. J Neurosurg. 2006. 105:5 Suppl. 418–424.

21. Okada H, Low KL, Kohanbash G, McDonald HA, Hamilton RL, Pollack IF. Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas. J Neurooncol. 2008. 88:245–250.

22. Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, Brat DJ, Rosenblum MK, Hamilton RL, Lavey RS, Heideman RL. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol. 2011. 13:317–323.

23. Ater J, Holmes E, Zhou T, Mazewski C, Roberts W, Vezina G, Booth T, Freyer D, Kadota R, Jakacki R, Packer R, Prados M, Pollack I. Results of COG protocol A9952: a randomized phase 3 study of two chemotherapy regimens for imcompletely resected low-grade glioma in young children. Neuro Oncol. 2008. 10:451–452.

24. Lee MJ, Ra YS, Park JB, Goo HW, Ahn SD, Khang SK, Song JS, Kim YJ, Ghim TT. Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide, in the treatment of low-grade gliomas in children. J Neurooncol. 2006. 80:277–284.

25. Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010. 363:1801–1811.

26. Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW. Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol. 2009. 27:385–389.

27. Tekautz TM, Fuller CE, Blaney S, Fouladi M, Broniscer A, Merchant TE, Krasin M, Dalton J, Hale G, Kun LE, Wallace D, Gilbertson RJ, Gajjar A. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol. 2005. 23:1491–1499.

28. Timmermann B, Kortmann RD, Kühl J, Meisner C, Dieckmann K, Pietsch T, Bamberg M. Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol. 2002. 20:842–849.

29. Marec-Berard P, Jouvet A, Thiesse P, Kalifa C, Doz F, Frappaz D. Supratentorial embryonal tumors in children under 5 years of age: an SFOP study of treatment with postoperative chemotherapy alone. Med Pediatr Oncol. 2002. 38:83–90.

30. Chintagumpala M, Hassall T, Palmer S, Ashley D, Wallace D, Kasow K, Merchant TE, Krasin MJ, Dauser R, Boop F, Krance R, Woo S, Cheuk R, Lau C, Gilbertson R, Gajjar A. A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET. Neuro Oncol. 2009. 11:33–40.

31. Kyritsis AP. Management of primary intracranial germ cell tumors. J Neurooncol. 2010. 96:143–149.

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