Seminars in Oncology
Volume 31, Issue 5 , Pages 666-675 , October 2004

Current treatment of medulloblastoma: Recent advances and future challenges

  • Brian R. Rood

      Affiliations

    • Division of Hematology/Oncology, Center for Cancer Research, Children’s National Medical Center, Washington, DC, USA.
    • Corresponding Author InformationAddress reprint requests to Brian R. Rood, MD, Division of Hematology/Oncology, 111 Michigan Ave, NW, Washington, DC 20010.
    • ,
  • Tobey J. MacDonald

      Affiliations

    • Division of Hematology/Oncology, Center for Cancer Research, Children’s National Medical Center, Washington, DC, USA.
    • ,
  • Roger J. Packer

      Affiliations

    • Division of Hematology/Oncology, Center for Cancer Research, Children’s National Medical Center, Washington, DC, USA.

References 

  1. CBTRUS . 1995–1999 Statistical Report (Primary Brain Tumors in the United States) . Hinsdale, IL: Central Brain Tumor Registry of the United States; 2002;
  2. Chan AW , Tarbell NJ , Black PM , et al.   Adult medulloblastoma (Prognostic factors and patterns of relapse) . Neurosurgery . 2000;47:623–631
  3. Allen JC , Epstein F . Medulloblastoma and other primary malignant neuroectodermal tumors of the CNS. The effect of patients’ age and extent of disease on prognosis . J Neurosurg . 1982;57:446–451
  4. Deutsch M , Reigel DH . The value of myelography in the management of childhood medulloblastoma . Cancer . 1980;45:2194–2197
  5. Bloom HJ . Medulloblastoma (Prognosis and prospects) . Int J Radiat Oncol Biol Phys . 1977;2:1031–1033
  6. Evans AE , Jenkin RD , Sposto R , et al.   The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone . J Neurosurg . 1990;72:572–582
  7. Vezina LG , Packer RJ . Infratentorial brain tumors of childhood . Neuroimaging Clin North Am . 1994;4:423–436
  8. MacDonald TJ , Rood BR , Santi MR , et al.   Advances in the diagnosis, molecular genetics, and treatment of pediatric embryonal CNS tumors . Oncologist . 2003;8:174–186
  9. Giangaspero F , Bigner S , Kleihues P . Medulloblastoma . In:  Kleihues P ,  Cavenee W editor. Pathology and Genetics: Tumours of the Nervous System: World Health Organization Classification of Tumours . Lyon, France: IARC Press; 2000;p. 129–139
  10. Pietsch T , Waha A , Koch A , et al.   Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of drosophila patched . Cancer Res . 1997;57:2085–2088
  11. Pomeroy SL , Tamayo P , Gaasenbeek M , et al.   Prediction of central nervous system embryonal tumour outcome based on gene expression . Nature . 2002;415:436–442
  12. Brown HG , Kepner JL , Perlman EJ , et al.   “Large cell/anaplastic” medulloblastomas (A Pediatric Oncology Group study) . J Neuropathol Exp Neurol . 2000;59:857–865
  13. Segal RA , Goumnerova LC , Kwon YK , et al.   Expression of the neurotrophin receptor trkc is linked to a favorable outcome in medulloblastoma . Proc Natl Acad Sci USA . 1994;91:12867–12871
  14. Grotzer MA , Janss AJ , Fung K , et al.   Trkc expression predicts good clinical outcome in primitive neuroectodermal brain tumors . J Clin Oncol . 2000;18:1027–1035
  15. Kim JY , Sutton ME , Lu DJ , et al.   Activation of neurotrophin-3 receptor trkc induces apoptosis in medulloblastomas . Cancer Res . 1999;59:711–719
  16. Gilbertson RJ , Pearson AD , Perry RH , et al.   Prognostic significance of the c-erbb-2 oncogene product in childhood medulloblastoma . Br J Cancer . 1995;71:473–477
  17. Gilbertson RJ , Perry RH , Kelly PJ , et al.   Prognostic significance of her2 and her4 coexpression in childhood medulloblastoma . Cancer Res . 1997;57:3272–3280
  18. MacDonald TJ , Brown KM , LaFleur B , et al.   Expression profiling of medulloblastoma (PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease) . Nat Genet . 2001;29:143–152
  19. Andrae J , Hansson I , Afink GB , et al.   Platelet-derived growth factor receptor-alpha in ventricular zone cells and in developing neurons . Mol Cell Neurosci . 2001;17:1001–1013
  20. Grotzer MA , Hogarty MD , Janss AJ , et al.   Myc messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma . Clin Cancer Res . 2001;7:2425–2433
  21. Herms J , Neidt I , Luscher B , et al.   C-myc expression in medulloblastoma and its prognostic value . Int J Cancer . 2000;89:395–402
  22. Raffel C , Jenkins RB , Frederick L , et al.   Sporadic medulloblastomas contain Ptch mutations . Cancer Res . 1997;57:842–845
  23. Dong J , Gailani MR , Pomeroy SL , et al.   Identification of patched mutations in medulloblastomas by direct sequencing . Hum Mutat . 2000;16:89–90
  24. Wetmore C , Eberhart DE , Curran T . Loss of p53 but not Arf accelerates medulloblastoma in mice heterozygous for patched . Cancer Res . 2001;61:513–516
  25. Taipale J , Chen JK , Cooper MK , et al.   Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine . Nature . 2000;406:1005–1009
  26. Taylor MD , Liu L , Raffel C , et al.   Mutations in Sufu predispose to medulloblastoma . Nat Genet . 2002;31:306–310
  27. Liu J , Guo L , Luo Y , et al.   All trans-retinoic acid suppresses in vitro growth and down-regulates Lif gene expression as well as telomerase activity of human medulloblastoma cells . Anticancer Res . 2000;20:2659–2664
  28. Hallahan AR , Pritchard JI , Chandraratna RA , et al.   Bmp-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect . Nat Med . 2003;9:1033–1038
  29. Wales MM , Biel MA , el Deiry W , et al.   P53 activates expression of Hic-1, a new candidate tumour suppressor gene on 17p13.3 . Nat Med . 1995;1:570–577
  30. Rood BR , Zhang H , Weitman DM , et al.   Hypermethylation of Hic-1 and 17p allelic loss in medulloblastoma . Cancer Res . 2002;62:3794–3797
  31. Biegel JA . Cytogenetics and molecular genetics of childhood brain tumors . Neurooncology . 1999;1:139–151
  32. Bayani J , Zielenska M , Marrano P , et al.   Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping . J Neurosurg . 2000;93:437–448
  33. Gajjar A , Fouladi M , Walter AW , et al.   Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors . J Clin Oncol . 1999;17:1825–1828
  34. Packer RJ , Cogen P , Vezina G , et al.   Medulloblastoma (Clinical and biologic aspects) . Neurooncology . 1999;1:232–250
  35. Deutsch M . Medulloblastoma (Staging and treatment outcome) . Int J Radiat Oncol Biol Phys . 1988;14:1103–1107
  36. Saran FH , Driever PH , Thilmann C , et al.   Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation . Int J Radiat Oncol Biol Phys . 1998;42:959–967
  37. Duffner PK , Horowitz ME , Krischer JP , et al.   Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors . N Engl J Med . 1993;328:1725–1731
  38. Albright AL , Wisoff JH , Zeltzer PM , et al.   Effects of medulloblastoma resections on outcome in children (A report from the Children’s Cancer Group) . Neurosurgery . 1996;38:265–271
  39. Packer RJ , Sutton LN , Elterman R , et al.   Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy . J Neurosurg . 1994;81:690–698
  40. Packer RJ , Rood BR , MacDonald TJ . Medulloblastoma (Present concepts of stratification into risk groups) . Pediatr Neurosurg . 2003;39:60–67
  41. Bouffet E , Gentet JC , Doz F , et al.   Metastatic medulloblastoma (The experience of the French Cooperative M7 Group) . Eur J Cancer . 1994;10:1478–1483
  42. Kortmann RD , Kuhl J , Timmermann B , et al.   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
  43. Zeltzer PM , Boyett JM , Finlay JL , et al.   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
  44. Pollack IF , Polinko P , Albright AL , et al.   Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children (Incidence and pathophysiology) . Neurosurgery . 1995;37:885–893
  45. Patterson RFR . Cerebellar medulloblastomas (Treatment by irradiation of the whole central nervous system) . Acta Radiol . 1953;39:323–336
  46. Deutsch M , Thomas PR , Krischer J , et al.   Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cgy/20) with reduced neuraxis irradiation (2,340 cgy/13) in patients with low-stage medulloblastoma. A combined Children’s Cancer Group-Pediatric Oncology Group study . Pediatr Neurosurg . 1996;24:167–176
  47. Thomas PR , Deutsch M , Kepner JL , et al.   Low-stage medulloblastoma (Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation) . J Clin Oncol . 2000;18:3004–3011
  48. Prados MD , Wara WM , Edwards MS , et al.   Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors (Early results of a pilot study) . Int J Radiat Oncol Biol Phys . 1994;28:431–438
  49. Allen JC , Donahue B , DaRosso R , et al.   Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors . Int J Radiat Oncol Biol Phys . 1996;36:1155–1161
  50. Huang E , Teh BS , Strother DR , et al.   Intensity-modulated radiation therapy for pediatric medulloblastoma (Early report on the reduction of ototoxicity) . Int J Radiat Oncol Biol Phys . 2002;52:599–605
  51. Tait DM , Thornton-Jones H , Bloom HJ , et al.   Adjuvant chemotherapy for medulloblastoma (The first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I)) . Eur J Cancer . 1990;26:464–469
  52. McIntosh S , Chen M , Sartain PA , et al.   Adjuvant chemotherapy for medulloblastoma . Cancer . 1985;56:1316–1319
  53. Strother D , Ashley D , Kellie SJ , et al.   Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy (Results of a collaborative study) . J Clin Oncol . 2001;19:2696–2704
  54. Taylor RE , Bailey CC , Robinson K , et al.   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
  55. Kunschner LJ , Kuttesch J , Hess K , et al.   Survival and recurrence factors in adult medulloblastoma (The M.D. Anderson cancer center experience from 1978 to 1998) . Neurooncology . 2001;3:167–173
  56. Packer RJ , Goldwein J , Nicholson HS , et al.   Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy (A Children’s Cancer Group study) . J Clin Oncol . 1999;17:2127–2136
  57. Goldwein JW , Radcliffe J , Johnson J , et al.   Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma) . Int J Radiat Oncol Biol Phys . 1996;34:899–904
  58. Geyer JR , Zeltzer PM , Boyett JM , et al.   Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day (A report from the Childrens Cancer Group) . J Clin Oncol . 1994;12:1607–1615
  59. Mason WP , Grovas A , Halpern S , et al.   Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors . J Clin Oncol . 1998;16:210–221
  60. Dupuis-Girod S , Hartmann O , Benhamou E , et al.   Will high dose chemotherapy followed by autologous bone marrow transplantation supplant cranio-spinal irradiation in young children treated for medulloblastoma? . J Neurooncol . 1996;27:87–98
  61. Finlay JL , Goldman S , Wong MC , et al.   Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children’s Cancer Group . J Clin Oncol . 1996;14:2495–2503
  62. Dunkel IJ , Boyett JM , Yates A , et al.   High-dose carboplatin, thiotepa, and etoposide with autologous stem- cell rescue for patients with recurrent medulloblastoma. Children’s Cancer Group . J Clin Oncol . 1998;16:222–228
  63. Packer RJ , Meadows AT , Rorke LB , et al.   Long-term sequelae of cancer treatment on the central nervous system in childhood . Med Pediatr Oncol . 1987;15:241–253
  64. Packer RJ , Sutton LN , Atkins TE , et al.   A prospective study of cognitive function in children receiving whole- brain radiotherapy and chemotherapy (2-year results) . J Neurosurg . 1989;70:707–713
  65. Ris MD , Packer R , Goldwein J , et al.   Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma (A Children’s Cancer Group study) . J Clin Oncol . 2001;19:3470–3476
  66. Packer RJ , Boyett JM , Janss AJ , et al.   Growth hormone replacement therapy in children with medulloblastoma (Use and effect on tumor control) . J Clin Oncol . 2001;19:480–487
  67. Goldstein AM , Yuen J , Tucker MA . Second cancers after medulloblastoma (Population-based results from the United States and Sweden) . Cancer Causes Control . 1997;8:865–871

PII: S0093-7754(04)00331-8

doi: 10.1053/j.seminoncol.2004.07.009

Seminars in Oncology
Volume 31, Issue 5 , Pages 666-675 , October 2004

Article Tools

* Image Usage & Resolution