Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Treatment Options in Neurology
Published in: Current Treatment Options in Neurology 4/2012

01-08-2012 | NEURO-ONCOLOGY (NEUROPLASMS) (M ROSENFELD, SECTION EDITOR)

Medulloblastoma

Authors: Katja von Hoff, MD, Stefan Rutkowski, MD

Published in: Current Treatment Options in Neurology | Issue 4/2012

Login to get access

Opinion statement

The mainstay of medulloblastoma treatment is high-quality interdisciplinary collaboration in diagnosis, treatment, and aftercare by all involved disciplines. The first step in treatment of medulloblastoma is a maximal safe surgery, followed by thorough staging. Surgery should only be performed in experienced neurosurgical centers, with age-appropriate postoperative care. As optimal risk stratification is based on histopathological and neuroradiological assessments, these should be performed or confirmed by experienced specialists. Central review of histopathological subtype, as well as review of staging evaluations is highly desirable. For young children with desmoplastic/nodular (DMB), or extensive nodular medulloblastoma, craniospinal or any radiotherapy should be avoided. For young children with classic medulloblastoma (CMB), large cell, or anaplastic medulloblastoma (LC/A MB) optimized strategies with high-dose chemotherapy and autologous stem cell rescue with or without local radiotherapy are under investigation. For older clinical standard risk patients (without metastases, without postoperative residual tumor >1.5 cm2) with CMB or DMB, craniospinal radiotherapy with 23.4 Gy and boost to the posterior fossa to 54 Gy, followed by maintenance chemotherapy can be regarded as a standard therapy besides other currently applied regimen, such as the use of intensified chemotherapy after irradiation. Older children with LC/A MB, metastatic medulloblastoma, and/or large residual tumor can be regarded as high-risk patients and should receive intensified treatment: intensified chemotherapeutic regimen before or after radiotherapy with increased dose (36-Gy CSI normofractionated, or 40-Gy hyperfractionated) is used. For treatment to be effective, quality control of radiotherapy is of high relevance. Information on long-term sequelae is essential and appropriate multidisciplinary follow-up and support, including rehabilitation and help for reintegration, is necessary. Whenever possible, patients should be included in prospective studies, and tumor material should be sampled to facilitate further research on medulloblastoma biology, which will significantly influence the stratification criteria and the introduction of targeted therapies in standard treatment recommendations in the future.
Literature
1.
Kaatsch P, Rickert CH, Kuhl J, et al. Population-based epidemiologic data on brain tumors in German children. Cancer. 2001;92(12):3155–64.PubMedCrossRef
2.
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(4):464–9.PubMed
3.
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(4):572–82.PubMedCrossRef
4.
Bailey CC, Gnekow A, Wellek S, et al. 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. 1995;25(3):166–78.PubMedCrossRef
5.
Louis DN, Ohgaki H, Wiestler O, et al., editors. WHO Classification of tumours of the central nervous system. Lyon: IARC; 2007.
6.••
Rutkowski S, von Hoff K, Emser A, et al. Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. J Clin Oncol 2010:28(33):4961–4968.PubMedCrossRef
7.
Brown HG, Kepner JL, Perlman EJ, et al. “Large cell/anaplastic” medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol. 2000;59(10):857–65.PubMed
8.
Giangaspero F, Wellek S, Masuoka J, et al. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol (Berl). 2006;112(1):5–12.CrossRef
9.••
Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012:123(4):465–472.PubMedCrossRef
10.
Thompson MC, Fuller C, Hogg TL, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol. 2006;24(12):1924–31.PubMedCrossRef
11.
Kool M, Koster J, Bunt J, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One. 2008;3(8):e3088.PubMedCrossRef
12.
Northcott PA, Korshunov A, Witt H, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 2010;29(11):1408–14.PubMedCrossRef
13.
Rausch T, Jones DT, Zapatka M, et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell. 2012;148(1–2):59–71.PubMedCrossRef
14.
Monje M, Beachy PA, Fisher PG. Hedgehogs, flies, Wnts and MYCs: the time has come for many things in medulloblastoma. J Clin Oncol. 2011;29(11):1395–8.PubMedCrossRef
15.
Wells EM, Khademian ZP, Walsh KS, et al. Postoperative cerebellar mutism syndrome following treatment of medulloblastoma: neuroradiographic features and origin. J Neurosurg Pediatr. 2010;5(4):329–34.PubMedCrossRef
16.•
Gudrunardottir T, Sehested A, Juhler M, et al. Cerebellar mutism: review of the literature. Childs Nerv Syst 2011:27(3):355–363.PubMedCrossRef
17.
Robertson PL, Muraszko KM, Holmes EJ, et al. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg. 2006;105(6 Suppl):444–51.PubMed
18.
Garre ML, Cama A, Bagnasco F, et al. Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome–a new clinical perspective. Clin Cancer Res. 2009;15(7):2463–71.PubMedCrossRef
19.
Bhatia R, Tahir M, Chandler CL. The management of hydrocephalus in children with posterior fossa tumours: the role of pre-resectional endoscopic third ventriculostomy. Pediatr Neurosurg. 2009;45(3):186–91.PubMedCrossRef
20.
21.
Due-Tonnessen BJ, Helseth E. Management of hydrocephalus in children with posterior fossa tumors: role of tumor surgery. Pediatr Neurosurg. 2007;43(2):92–6.PubMedCrossRef
22.
Riva-Cambrin J, Detsky AS, Lamberti-Pasculli M, et al. Predicting postresection hydrocephalus in pediatric patients with posterior fossa tumors. J Neurosurg Pediatr. 2009;3(5):378–85.PubMedCrossRef
23.
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(24):1725–31.PubMedCrossRef
24.
Rutkowski S, Gerber NU, von Hoff K, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol. 2009;11(2):201–10.PubMedCrossRef
25.
Rutkowski S, Bode U, Deinlein F, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005;352(10):978–86.PubMedCrossRef
26.
Geyer JR, Sposto R, Jennings M, et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol. 2005;23(30):7621–31.PubMedCrossRef
27.
Grill J, Sainte-Rose C, Jouvet A, et al. Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol. 2005;6(8):573–80.PubMedCrossRef
28.
Grundy RG, Wilne SH, Robinson KJ, et al. Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial. Eur J Cancer. 2010;46(1):120–33.PubMedCrossRef
29.
Dhall G, Grodman H, Sands S, et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer. 2008;50(6):1169–75.
30.
von Bueren AO, von Hoff K, Pietsch T, et al. 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. 2011;13(6):669–79.CrossRef
31.
Leary SE, Zhou T, Holmes E, et al. Histology predicts a favorable outcome in young children with desmo-plastic medulloblastoma: a report from the children’s oncology group. Cancer. 2011;117(14):3262–3267.
32.
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(3):832–45.PubMed
33.•
Lannering B, Rutkowski S, doz F, et al. HIT-SIOP PNET4 - A randomised multicentre study of hyperfractionated (HFRT) versus standard radiotherapy (STRT) in children with standard risk medulloblastoma. Neuro-Oncol. 2010;6(12):ii5 (abstr). This prospective, randomized trial compared the use of conventional and hyperfractionated radiotherapy for treatment of standard risk medulloblastoma patients. Clinical risk factors were analyzed.
34.
Warmuth-Metz M, Bison B, Leykamm S. Neuroradiologic review in pediatric brain tumor studies. Klin Neuroradiol. 2009;19(4):263–73.PubMedCrossRef
35.
Knauth M, Aras N, Wirtz CR, et al. Surgically induced intracranial contrast enhancement: potential source of diagnostic error in intraoperative MR imaging. AJNR Am J Neuroradiol. 1999;20(8):1547–53.PubMed
36.
Chang CH, Housepian EM, Herbert Jr C. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology. 1969;93(6):1351–9.PubMed
37.
Gajjar A, Chintagumpala M, Ashley D, et al. 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. 2006;7(10):813–20.PubMedCrossRef
38.
von Hoff K, Hinkes B, Gerber NU, et al. Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer. 2009;45(7):1209–17.CrossRef
39.
Verlooy J, Mosseri V, Bracard S, et al. Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study. Eur J Cancer. 2006;42(17):3004–14.PubMedCrossRef
40.
Warmuth-Metz M, Kuhl J, Krauss J, et al. Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours. Neuroradiology. 2004;46(3):219–23.PubMedCrossRef
41.
Northcott PA, Hielscher T, Dubuc A, et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol. 2011;122(2):231–40.PubMedCrossRef
42.
von Hoff K, Hartmann W, von Bueren AO, et al. Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors. Pediatr Blood Cancer. 2009;54(3):369–76.CrossRef
43.
Eberhart CG, Kratz J, Wang Y, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63(5):441–9.PubMed
44.
Ryan SL, Schwalbe EC, Cole M, et al. MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma. Acta Neuropathol. 2012;123(4):501–513.
45.
Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24(25):4202–8.PubMedCrossRef
46.
Merchant TE, Kun LE, Krasin MJ, et al. Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma. Int J Radiat Oncol Biol Phys. 2008;70(3):782–7.PubMedCrossRef
47.
Gandola L, Massimino M, Cefalo G, et al. Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol. 2009;27(4):566–71.PubMedCrossRef
48.
Mulhern RK, Palmer SL, Merchant TE, et al. Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol. 2005;23(24):5511–9.PubMedCrossRef
49.
Grill J, Renaux VK, Bulteau C, et al. Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes. Int J Radiat Oncol Biol Phys. 1999;45(1):137–45.PubMedCrossRef
50.
Carrie C, Hoffstetter S, Gomez F, et al. Impact of targeting deviations on outcome in medulloblastoma: study of the French Society of Pediatric Oncology (SFOP). Int J Radiat Oncol Biol Phys. 1999;45(2):435–9.PubMedCrossRef
51.
Oyharcabal-Bourden V, Kalifa C, Gentet JC, et al. Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study. J Clin Oncol. 2005;23(21):4726–34.PubMedCrossRef
52.
Carrie C, Grill J, Figarella-Branger D, et al. Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: long-term results of MSFOP 98. J Clin Oncol. 2009;27(11):1879–83.PubMedCrossRef
53.
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(7):2127–36.PubMed
54.
Duffner PK. Risk factors for cognitive decline in children treated for brain tumors. Eur J Paediatr Neurol. 2010;14(2):106–15.PubMedCrossRef
55.
Palmer SL. Neurodevelopmental impact on children treated for medulloblastoma: a review and proposed conceptual model. Dev Disabil Res Rev. 2008;14(3):203–10.PubMedCrossRef
56.
Butler RW, Sahler OJ, Askins MA, et al. Interventions to improve neuropsychological functioning in childhood cancer survivors. Dev Disabil Res Rev. 2008;14(3):251–8.PubMedCrossRef
57.
Frange P, Alapetite C, G Gaboriaud, et al. From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980–2000). J Neurooncol. 2009;95(2):271–9.PubMedCrossRef
58.
Puget S, Boddaert N, Viguier D, et al. Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors. Cancer. 2009;115(6):1338–47.PubMedCrossRef
59.
Ribi K, Relly C, Landolt MA, et al. Outcome of medulloblastoma in children: long-term complications and quality of life. Neuropediatrics. 2005;36(6):357–65.PubMedCrossRef
60.
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(2):269–79.PubMedCrossRef
61.
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(2):480–7.PubMed
62.
Goldstein AM, Yuen J, Tucker MA. Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes Control. 1997;8(6):865–71.PubMedCrossRef
Metadata
Title
Medulloblastoma
Authors
Katja von Hoff, MD
Stefan Rutkowski, MD
Publication date
01-08-2012
Publisher
Current Science Inc.
Published in
Current Treatment Options in Neurology / Issue 4/2012
Print ISSN: 1092-8480
Electronic ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-012-0183-8

Other articles of this Issue 4/2012

Current Treatment Options in Neurology 4/2012 Go to the issue

EPILEPSY (E WATERHOUSE, SECTION EDITOR)

Treatment of Post-Traumatic Epilepsy

NEURO-ONCOLOGY (NEUROPLASMS) (M ROSENFELD, SECTION EDITOR)

Recent Innovations in the Management of Low-Grade Gliomas

NEURO-ONCOLOGY (NEUROPLASMS) (M ROSENFELD, SECTION EDITOR)

Leptomeningeal Metastases

EPILEPSY (E WATERHOUSE, SECTION EDITOR)

Antiepileptic Drug Selection for Partial-Onset Seizures

NEURO-ONCOLOGY (NEUROPLASMS) (M ROSENFELD, SECTION EDITOR)

Anaplastic Glioma

EPILEPSY (E WATERHOUSE, SECTION EDITOR)

Managing Epilepsy During Pregnancy: Assessing Risk and Optimizing Care