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Treatment of Medulloblastoma: Chemotherapy

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Posterior Fossa Tumors in Children

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Abstract

Medulloblastoma (MB) is one of the most common malignant brain tumors in childhood. Its origin is from the cerebellar vermis or from one of cerebellar hemispheres. Its extracerebellar counterparts are the primitive neuroectodermal tumors known as PNETs. Among pediatric embryonal central nervous system tumors, MB generally shows a better prognosis with 5-year survival rates of up to 70 % in standard-risk patients. The standard risk identifies patients fulfilling following criteria: total or subtotal resection, age over 3 years, and localized disease without dissemination. Chemotherapy modified the prognosis of MB since 1976 when the first trial of the International Society of Paediatric Oncology (SIOP I) introduced adjuvant chemotherapy (vincristine, lomustine, and prednisone). Now, we consider MB a chemoresponsive tumor and chemotherapy plays a role together with surgery and radiotherapy. Resistance to treatments is on study: biological differences may explain different behavior of neoplastic cells and different fates between patients inside the same risk group. Ongoing research will point to the knowledge of deregulation of embryogenetic signalling pathways involved in the pathogenesis of MB and in self-maintenance of tumoral stem cells. Future therapeutic trials will have different stratification of patients based on biological markers.

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References

  1. Michiels EMC, Schouten-Van Meeteren AYN, Doz F et al (2010) Chemotherapy for children with medulloblastoma (Protocol). Cochrane Lib 1:1–8

    Google Scholar 

  2. Peris-Bonet R, Martinez-Garcia C, Lacour B et al (2006) Childhood central nervous system tumours-incidence and survival in Europe (1978–1997): report from Automated Childhood Cancer Information System project. Eur J Cancer 42:2064–2080

    Google Scholar 

  3. Gatta G, Zigon G, Capocaccia R et al (2009) Survival of European children and young adults with cancer diagnosed 1995–2002. Eur J Cancer 45:992–1005

    Article  PubMed  Google Scholar 

  4. Packer RJ, Rood BR, MacDonald TJ (2003) Medulloblastoma: present concepts of stratification into risk groups. Pediatr Neurosurg 39:60–67

    Article  PubMed  Google Scholar 

  5. Gajjar A, Hernan R, Kocak M et al (2004) Clinical, histopathologic and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22(6):984–993

    Article  CAS  PubMed  Google Scholar 

  6. Eberhart CG, Kepner JL, Goldthwaite PT et al (2000) Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer 94(2):552–560

    Article  Google Scholar 

  7. Massimino M, Antonelli M, Gandola L et al (2013) Histological variants of medulloblastoma are the most powerful clinical prognostic indicators. Pediatr Blood Cancer 60(2):210–216

    Article  PubMed  Google Scholar 

  8. McManamy CS, Lamont JM, Taylor RE et al (2003) Morphophenotypic variation predicts clinical behavior in childhood non-desmoplastic medulloblastomas. J Neuropathol Exp Neurol 62(6):627–632

    PubMed  Google Scholar 

  9. Von Bueren AO, Von Hoff K, Pietsch T et al (2011) Treatment of young children with localized medulloblastoma by chemotherapy alone: Results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro Oncol 13(6):669–679

    Article  Google Scholar 

  10. Taylor MD, Northcott P, Korshunov A et al (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123(4):465–472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Pietsch T, Schmidt R, Remke M et al (2014) Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 128(1):137–149

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Pizzo PA, Poplack DG (2011) Principles and practice of pediatric oncology. Lippincott Williams & Wilkins/Wolters Kluwer Business, Philadelphia

    Google Scholar 

  13. Bailey CC, Gnekow A, Wellek S et al (1995) Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol 25:166–178

    Article  CAS  PubMed  Google Scholar 

  14. Jakacki RI, Feldman H, Jamison C et al (2004) A pilot study of preirradiation chemotherapy and 1800 cGy craniospinal irradiation in young children with medulloblastoma. Int J Radiat Oncol Biol Phys 60(2):531–536

    Google Scholar 

  15. Taylor RE, Bailey CC, Robinson KJ et al (2005) Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer 41:727–734

    Article  CAS  PubMed  Google Scholar 

  16. Packer RJ, Goldwein J, Nicholson HS et al (1999) Treatment of children with medulloblastoma with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children’s Cancer Group study. J Clin Oncol 17(7):2127–2136

    CAS  PubMed  Google Scholar 

  17. Packer RJ, Gajjiar A, Vezina G et al (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24(25):4202–4208

    Article  CAS  PubMed  Google Scholar 

  18. Rutkowski S, Bode U, Deinlein F et al (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986

    Article  CAS  PubMed  Google Scholar 

  19. Pérez-Martinez A, Quintero V, Vicent MG et al (2004) High-dose chemotherapy with autologous stem cell rescue as first line of treatment in young children with medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol 67:101–106

    Article  PubMed  Google Scholar 

  20. Grill J, Sainte-Rose C, Jouvet A et al (2005) Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6:573–580

    Article  CAS  PubMed  Google Scholar 

  21. Massimino M, Giangaspero F, Garrè ML et al (2011) Childhood medulloblastoma. Crit Rev Oncol Hematol 79(1):65–83, Epub 2010 Dec 3

    Article  PubMed  Google Scholar 

  22. Lannering B, Rutkowski S, Doz F et al (2012) Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomised multicenter HIT-SIOP PNET 4 trial. J Clin Oncol 30(26):3187–3193

    Article  PubMed  Google Scholar 

  23. Carrie C, Muracciole X, Gomez F et al (2005) Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol Biol Phys 63:711–716

    Article  PubMed  Google Scholar 

  24. Gajjar A, Chintagumpala M, Ashley D et al (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St. Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7(10):813–820

    Article  PubMed  Google Scholar 

  25. Packer RJ, Siegel KR, Sutton LN et al (1988) Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Ann Neurol 24:503–508

    Article  CAS  PubMed  Google Scholar 

  26. Verlooy J, Mosseri V, Bracard S et al (2006) Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study. Eur J Cancer 42:3004–3014

    Article  CAS  PubMed  Google Scholar 

  27. Zeltzer PM, Boyett JM, Finlay JL et al (1999) 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 17:832–845

    CAS  PubMed  Google Scholar 

  28. Kortmann RD, Kuhl J, Timmermann B et al (2000) 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 46:269–279

    Article  CAS  PubMed  Google Scholar 

  29. Strother D, Ashley D, Kellie SJ et al (2001) 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 19:2696–2704

    CAS  PubMed  Google Scholar 

  30. Dhodapkar K, Dunkel IJ, Gardner S et al (2002) Preliminary results of dose intensive pre-irradiation chemotherapy in patients older than 10 years of age with high risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Med Pediatr Oncol 38:47–48

    Article  PubMed  Google Scholar 

  31. Chi SN, Gardner SL, Levy AS et al (2004) Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol 22:4881–4887

    Article  CAS  PubMed  Google Scholar 

  32. Gandola L, Massimino M, Cefalo G et al (2009) Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol 27:566–571

    Article  CAS  PubMed  Google Scholar 

  33. Duffner PK, Horowitz ME, Krischer JP et al (1993) Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328:1725–1731

    Article  CAS  PubMed  Google Scholar 

  34. Ater JL, van Eys J, Woo SY et al (1997) MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. J Neurooncol 32:243–252

    Article  CAS  PubMed  Google Scholar 

  35. Garrè ML, Massimino M, Cefalo G et al (2003) High-risk malignant CNS tumours in infants: standard vs myeloablative chemotherapy: the experience of the Italian cooperative study for children <3 years of age. Neuro Oncol 1:40

    Google Scholar 

  36. Rutkowski S, Gerber NU, von Hoff K et al (2009) Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol 11:201–210

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Duffner PK, Horowitz ME, Krischer JP et al (1999) The treatment of malignant brain tumors in infants and very young children: an update of the Pediatric Oncology Group experience. Neuro Oncol 1:152–161

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Geyer JR, Sposto R, Jennings M et al (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23:7621–7631

    Article  PubMed  Google Scholar 

  39. Garrè ML, Cama A, Bagnasco F et al (2009) Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome–a new clinical perspective. Clin Cancer Res 15:2463–2471

    Article  PubMed  Google Scholar 

  40. Ridola V, Grill J, Doz F et al (2007) High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy. Cancer 110:156–163

    Article  PubMed  Google Scholar 

  41. Bouffet E, Doz F, Demaille MC et al (1998) Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse? Br J Cancer 77:1321–1326

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Massimino M, Gandola L, Spreafico F et al (2009) No salvage using high-dose chemotherapy plus/minus reirradiation for relapsing previously irradiated medulloblastoma. Int J Radiat Oncol Biol Phys 73:1358–1363

    Article  CAS  PubMed  Google Scholar 

  43. Saran F, Baumert BG, Creak AL et al (2008) Hypofractionated stereotactic radiotherapy in the management of recurrent or residual medulloblastoma/PNET. Pediatr Blood Cancer 50:554–560

    Article  PubMed  Google Scholar 

  44. Aguilera D, Mazewski C, Fangusaro J et al (2013) Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience. Childs Nerv Syst 29(4):589–596

    Article  PubMed Central  PubMed  Google Scholar 

  45. Kool M, Jones DTW, Jager N et al (2014) Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25(3):393–405

    Article  CAS  PubMed  Google Scholar 

  46. Gottardo NG, Hansford JR, McGlade JP et al (2014) Medulloblastoma down under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group. Acta Neuropathol 127:189–201

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Division of Pediatric Oncology, A.O.R.N. Santobono-Pausilipon Children’s Hospital, Via Posillipo n°226, 80123, Naples, Italy

    Lucia Quaglietta M.D., Virginia Vitale M.D., Antonio Verrico M.D. & Roberta Migliorati M.D.

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  1. Lucia Quaglietta M.D.
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  2. Virginia Vitale M.D.
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  3. Antonio Verrico M.D.
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  4. Roberta Migliorati M.D.
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Corresponding author

Correspondence to Lucia Quaglietta M.D. .

Editor information

Editors and Affiliations

  1. Neurosurgery, Acıbadem University, Istanbul, Istanbul, Turkey

    M. Memet Özek

  2. Pediatric Neurosurgery, Santobono Children's Hospital, Naples, Napoli, Italy

    Giuseppe Cinalli

  3. Dept. Neurosurgery, Royal Childrens Hospital, Melbourne, Victoria, Australia

    Wirginia Maixner

  4. Pediatric Neurosurgery, Hopital Necker-Enfants Malades, Paris, Paris, France

    Christian Sainte-Rose

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Quaglietta, L., Vitale, V., Verrico, A., Migliorati, R. (2015). Treatment of Medulloblastoma: Chemotherapy. In: Özek, M., Cinalli, G., Maixner, W., Sainte-Rose, C. (eds) Posterior Fossa Tumors in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-11274-9_18

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  • DOI: https://doi.org/10.1007/978-3-319-11274-9_18

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-11273-2

  • Online ISBN: 978-3-319-11274-9

  • eBook Packages: MedicineMedicine (R0)

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