Cancer Information

Childhood Medulloblastoma Treatment (PDQ®)


Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood medulloblastoma. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board.

Information about the following is included in this summary:

  • Cellular classification.
  • Stage information.
  • Treatment options.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version, which is written in less-technical language, and in Spanish. The PDQ childhood brain tumor treatment summaries are in the process of being substantially revised. This revision process was prompted by changes in the nomenclature and classification for pediatric central nervous system tumors. New PDQ childhood brain tumor treatment summaries will be added and some existing summaries will be replaced or their content combined with other PDQ childhood brain tumor treatment summaries in the near future.

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General Information

This PDQ summary contains content that is also included in the new PDQ Childhood Central Nervous System Embryonal Tumors summary. In the future, the PDQ Childhood Medulloblastoma summary will be removed from the National Cancer Institute's (NCI's) Cancer.gov Website, and the content contained in this summary will be found in the PDQ Childhood Central Nervous System Embryonal Tumors summary.

The NCI provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ Late Effects of Treatment for Childhood Cancer summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in the tumor diagnosis and classification.

Refer to the PDQ Childhood Brain and Spinal Cord Tumors Treatment Overview summary for information about the general classification of childhood brain and spinal cord tumors.

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Cellular Classification

The classification of brain tumors is based on both histopathological characteristics and location in the brain. Undifferentiated neuroectodermal tumors of the cerebellum have historically been referred to as medulloblastomas, while tumors of identical histology in the pineal region are diagnosed as pineoblastomas, and cortical lesions have been called central neuroblastomas or cortical primitive neuroectodermal tumors. There are different molecular genetic aberrations in the tumor cells of medulloblastomas and supratentorial primitive neuroectodermal tumors.[1][2][3] The nomenclature of pediatric brain tumors is controversial and potentially confusing. Some pathologists advocate abandoning the traditional morphologically based classifications such as medulloblastoma in favor of a terminology that relies more extensively on the phenotypic characteristics of the tumor. In such a system, medulloblastoma is referred to as primitive neuroectodermal tumor and then subdivided on the basis of cellular differentiation.[4][5][6][7] The most recent World Health Organization classification of brain tumors maintains the term medulloblastoma for posterior fossa undifferentiated tumors.[7][8] It also maintains separate categories for cerebral primitive neuroectodermal tumors and for pineal small round cell tumors (pineoblastomas). The pathologic classification of pediatric brain tumors is a specialized area that is undergoing evolution; review of the diagnostic tissue by a neuropathologist who has particular expertise in this area is strongly recommended.

1Russo C, Pellarin M, Tingby O, et al.: Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors. Cancer 86 (2): 331-9, 1999.2Nicholson JC, Ross FM, Kohler JA, et al.: Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours. Br J Cancer 80 (9): 1322-31, 1999.3Pomeroy SL, Tamayo P, Gaasenbeek M, et al.: Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415 (6870): 436-42, 2002.4Rorke LB: The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. J Neuropathol Exp Neurol 42 (1): 1-15, 1983.5Gilles FH: Classifications of childhood brain tumors. Cancer 56 (7 Suppl): 1850-7, 1985.6Dehner LP: Peripheral and central primitive neuroectodermal tumors. A nosologic concept seeking a consensus. Arch Pathol Lab Med 110 (11): 997-1005, 1986.7Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.8Burger PC, Scheithauer BW: Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology,1994.

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Stage Information

Medulloblastoma

This tumor usually originates in the cerebellum. It may spread contiguously to the cerebellar peduncle, floor of the fourth ventricle, into the cervical spine, or above the tentorium. In addition, it may spread via the cerebrospinal fluid (CSF) intracranially and/or to the spinal cord. Every patient with medulloblastoma should be evaluated with diagnostic imaging of the entire neuraxis, and when possible, lumbar CSF analysis for free-floating tumor cells.[1] The most sensitive method available for evaluating spinal cord subarachnoid metastasis is spinal magnetic resonance imaging performed with gadolinium. Because medulloblastoma occasionally metastasizes outside the central nervous system, especially to bone, a bone scan with plain film correlation as well as a bone marrow aspiration and biopsy may be useful in symptomatic patients or in those with abnormal blood cell counts at diagnosis. CSF shunts at the time of surgery have not been shown to increase the risk of leptomeningeal relapse. The most commonly used staging system has been proposed in a system that rates the tumor by an intraoperative evaluation of both size and extent as well as by the presence of metastatic disease. Alternative postoperative staging systems are now being used that are based on surgical impression and postoperative imaging studies. Patients with disseminated disease at diagnosis are clearly at highest risk for disease relapse.[2] Other factors that may portend an unfavorable outcome include younger age at diagnosis, brain stem involvement, subtotal resection, and anaplastic histologic features.[2][3][4][5] These prognostic variables must be evaluated in the context of the treatment received.

Biologic tumor characteristics have been associated with prognosis, though not all reports have consistently identified prognostic significance for the same markers. Nuclear expression of p53 and disruption of the p53/ARF tumor suppressor pathway, HER2/ErbB2 expression, and survivin expression have been associated with poor prognosis.[6][7][8][9] Amplification and overexpression of MYCC/MYCN have been associated with poor prognosis in some studies,[10][11][12][13][14] but not others.[8] Conversely, TrkC mRNA or protein expression has been linked to favorable outcome,[6][15] though not universally.[8] Gene expression profiling can also provide prognostic information that is independent of clinical variables.[16] There is no consensus for how these biological features should be applied to direct therapeutic decisions, though ongoing studies are seeking to provide data that will allow a valid risk classification scheme to be developed based on biological characteristics.[8][17]

Two major risk group categories defined by clinical criteria are now being used:

  • Average risk: Children older than 3 years with posterior fossa tumors; tumor is totally or near-totally resected (<1.5 cc of residual disease) ; no dissemination.[3]
  • High risk: Children aged 3 years and younger or those with metastatic disease and/or subtotal resection (>1.5 cc of residual disease) and/or nonposterior fossa location.[13]
1Fouladi M, Gajjar A, Boyett JM, et al.: Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 17 (10): 3234-7, 1999.2Albright AL, Wisoff JH, Zeltzer PM, et al.: Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery 38 (2): 265-71, 1996.3Yao MS, Mehta MP, Boyett JM, et al.: The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population. Int J Radiat Oncol Biol Phys 38 (3): 469-76, 1997.4Packer RJ, Siegel KR, Sutton LN, et al.: Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Ann Neurol 24 (4): 503-8, 1988.5Giangaspero F, Wellek S, Masuoka J, et al.: Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol 112 (1): 5-12, 2006.6Ray A, Ho M, Ma J, et al.: A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res 10 (22): 7613-20, 2004.7Frank AJ, Hernan R, Hollander A, et al.: The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell anaplastic medulloblastoma. Brain Res Mol Brain Res 121 (1-2): 137-40, 2004.8Gajjar A, Hernan R, Kocak M, et al.: Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22 (6): 984-93, 2004.9Haberler C, Slavc I, Czech T, et al.: Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome. Eur J Cancer 42 (17): 2996-3003, 2006.10Grotzer MA, Hogarty MD, Janss AJ, et al.: MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma. Clin Cancer Res 7 (8): 2425-33, 2001.11Aldosari N, Bigner SH, Burger PC, et al.: MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children's Oncology Group. Arch Pathol Lab Med 126 (5): 540-4, 2002.12Herms J, Neidt I, Lüscher B, et al.: C-MYC expression in medulloblastoma and its prognostic value. Int J Cancer 89 (5): 395-402, 2000.13Lamont JM, McManamy CS, Pearson AD, et al.: Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res 10 (16): 5482-93, 2004.14Eberhart 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 63 (5): 441-9, 2004.15Grotzer MA, Janss AJ, Fung K, et al.: TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J Clin Oncol 18 (5): 1027-35, 2000.16Fernandez-Teijeiro A, Betensky RA, Sturla LM, et al.: Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomas. J Clin Oncol 22 (6): 994-8, 2004.17Fisher PG, Burger PC, Eberhart CG: Biologic risk stratification of medulloblastoma: the real time is now. J Clin Oncol 22 (6): 971-4, 2004.

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Treatment Option Overview

Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those previously obtained with existing therapy.

Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, treatment planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Both surgery and radiation therapy of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in these areas in order to ensure optimal results. Less than optimal techniques have resulted in failure at the junction of the brain and spine radiation fields or in the cribriform plate region.[1] Patients should be treated in a center experienced with this therapy.

In the past, treatment has included surgery with radiation therapy. There is evidence to suggest that more extensive surgical resections are related to an improved rate of survival, primarily in children with nondisseminated posterior fossa disease at diagnosis. Chemotherapy has been shown to be active in patients with medulloblastomas. Prospective, randomized trials and large single-arm trials suggest that adjuvant chemotherapy given during and after radiation therapy improves overall survival for the subset of children with medulloblastoma who have less favorable prognostic factors, and there has been considerable data supporting the role of chemotherapy in the treatment of medulloblastoma.[2][3][4][5] Children aged 3 years and younger are particularly susceptible to the adverse effect of radiation on brain development. Debilitating effects on growth and neurologic development have frequently been observed, especially in younger children.[6][7][8][9] For this reason, the role of chemotherapy in allowing a delay in the administration of radiation therapy is under study, and preliminary results suggest that chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with medulloblastoma.[2][10] Surveillance testing is presently a part of all ongoing medulloblastoma studies.[11][12] Secondary tumors have increasingly been diagnosed in long-term survivors.[13][14][15] Long-term management of these patients is complex and requires a multidisciplinary approach.

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

1Carrie 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 45 (2): 435-9, 1999.2Duffner 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 328 (24): 1725-31, 1993.3Ater JL, van Eys J, Woo SY, et al.: MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. J Neurooncol 32 (3): 243-52, 1997.4Packer RJ, Sutton LN, Elterman R, et al.: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 81 (5): 690-8, 1994.5Taylor 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 21 (8): 1581-91, 2003.6Packer 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 70 (5): 707-13, 1989.7Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term survival in young children with medulloblastoma. J Neurosurg 80 (6): 1004-10, 1994.8Ris 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 19 (15): 3470-6, 2001.9Walter AW, Mulhern RK, Gajjar A, et al.: Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children's Research Hospital. J Clin Oncol 17 (12): 3720-8, 1999.10Mason 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 16 (1): 210-21, 1998.11Torres CF, Rebsamen S, Silber JH, et al.: Surveillance scanning of children with medulloblastoma. N Engl J Med 330 (13): 892-5, 1994.12Saunders DE, Hayward RD, Phipps KP, et al.: Surveillance neuroimaging of intracranial medulloblastoma in children: how effective, how often, and for how long? J Neurosurg 99 (2): 280-6, 2003.13Jenkin D: Long-term survival of children with brain tumors. Oncology (Huntingt) 10 (5): 715-9; discussion 720, 722, 728, 1996.14Goldstein AM, Yuen J, Tucker MA: Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes Control 8 (6): 865-71, 1997.15Stavrou T, Bromley CM, Nicholson HS, et al.: Prognostic factors and secondary malignancies in childhood medulloblastoma. J Pediatr Hematol Oncol 23 (7): 431-6, 2001.

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Untreated Childhood Medulloblastoma

Careful evaluation to determine fully the extent of disease must precede the treatment of medulloblastoma. Surgery should be an attempt at maximal tumor reduction; children without disseminated disease at diagnosis have improved progression-free survival if there is minimal residual disease present after surgery.[1] Surgery may be associated with temporary or permanent neurologic worsening due to postoperative infection, direct brain or cerebellar damage, or the development of the postoperative cerebellar mutism syndrome. This syndrome of delayed onset, typically hours after surgery, presents with mutism, emotional lability and usually hypotonia, dysphagia, ataxia supranuclear cranial neuropathy, and has been reported to occur in nearly 25% of patients. The etiology of posterior fossa mutism is unclear, but has been related to tumor brainstem invasion, and vermian damage and possibly disruption of the dentatothalamocortical pathways. It causes permanent sequelae in nearly one-half of all moderately to severely affected patients.[2] Postoperatively, studies should be conducted to determine whether the patient is at high risk of relapse. Risk criteria are outlined in the stage information section.[3][4] Patients with metastatic or significant local residual tumor should be considered at high risk for relapse and be treated on protocols specifically designed for them.

Treatment Options

The following describes treatment options by risk grouping:[4]

Average risk

The traditional postsurgical treatment for these patients has been radiation therapy consisting of 54 Gy to 55.8 Gy to the posterior fossa and approximately 36 Gy to the entire neuraxis (i.e., the whole brain and spine). While the standard boost in medulloblastoma is the entire posterior fossa, patterns of failure data suggest that the use of a tumor-bed boost would be equally effective [5] yet associated with reduced toxicity.[6][7] The minimal dose of radiation therapy needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 23.4 Gy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[8] The lower radiation dose to the neuraxis (23.4 Gy), when coupled with chemotherapy, has been shown to result in disease control in up to 80% of patients and may decrease the severity of neurocognitive sequelae.[9][10][11][12] Long-term survivors who were prepubertal at the time of diagnosis are at high risk for growth failure due to hypothalamic failure, and growth hormone replacement therapy has not been shown to increase the likelihood of disease relapse.[13]

Treatment options under clinical evaluation

The following is an example of a national and/or institutional clinical trial that is currently being conducted. For more information about clinical trials, please see the NCI Web site.

  • The Children's Oncology Group (COG) is coordinating a phase III trial (COG-ACNS0331) randomly assigning children between the ages of 3 years and 8 years to receive between 18 Gy and 24 Gy of craniospinal radiation, and also randomly assigning children between the ages of 3 years and 21 years to receive conformal tumor-site versus posterior-fossa radiation therapy. In this study, children receive weekly vincristine during radiation therapy and lomustine, vincristine, cisplatin, etoposide, and cyclophosphamide after radiation therapy.

High risk

In poor-risk patients, the addition of chemotherapy has improved the duration of disease-free survival.[12][14] Some studies show that approximately 50% to 65% of such patients will experience long-term disease control.[3] These are patients who, at diagnosis, have locally extensive and often unresectable tumor in the posterior fossa and/or noncontiguous metastatic disease within or outside of the central nervous system. Adjuvant chemotherapy has improved progression-free survival for patients with these high-risk parameters at diagnosis.[3][12][14][15] Such patients should be considered for entry into a clinical trial.[3][4] Long-term survivors who were prepubertal at the time of diagnosis are at high risk for growth failure due to hypothalamic failure, and growth hormone replacement therapy has not been shown to increase the likelihood of disease relapse.[13]

Children aged 3 years and younger

Because of the reluctance to use extensive radiation therapy (especially craniospinal radiation therapy) in young children due to concerns about resultant severe neurocognitive deficits, chemotherapy has been extensively explored in children aged 3 years and younger, and in some studies in children aged 6 years and younger, with medulloblastoma.[4][16][17] Different chemotherapeutic regimens have been employed, and most have utilized an alkylator (cyclophosphamide or ifosfamide), cisplatin and/or carboplatin, oral or intravenous etoposide, and vincristine. Outcome of such treatment has been relatively disappointing, resulting in disease control in only 20% to 30% of patients. In some of the earlier studies, craniospinal and local boost radiation therapy were utilized after completion of chemotherapy or when the children reached the age of 3 years.[16] Despite this approach, overall disease control still remained only in the 30% to 35% range. Most of the children who had long-term benefit were those who had nondisseminated, totally resected disease.

In attempts to make chemotherapy even more effective, other drugs have been added to these multiagent approaches, including intravenous and intraventricular methotrexate.[18] In patients who had nondisseminated tumors that were completely resected, 5-year progression-free survival after the addition of methotrexate was approximately 60%. Studies have been completed suggesting improved survival rates in a similar subset of children using higher-dose chemotherapy without methotrexate, supported by peripheral stem cell rescue.[19] Given its potential neurotoxicity, methotrexate remains a problematic drug to incorporate in the treatment of children with medulloblastoma. In one study that used high-dose methotrexate and intraventricular methotrexate, a high incidence of leukoencephalopathy was found, although the significance of such leukoencephalopathy as regards long-term neurocognitive outcome was unclear.[18] There seems to be a subset of patients who can be effectively treated with chemotherapy alone, and it is likely that the wider availability and application of molecular genetic markers will, in time, better identify this subset.[20] Another approach for children aged 3 years or younger at diagnosis with localized medulloblastoma is the use of multiagent chemotherapy followed by conformal radiation therapy to the primary tumor site. Results from this study are still pending.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated childhood medulloblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1Albright AL, Wisoff JH, Zeltzer PM, et al.: Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery 38 (2): 265-71, 1996.2Robertson 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 105 (6): 444-51, 2006.3Evans 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 72 (4): 572-82, 1990.4Geyer 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 12 (8): 1607-15, 1994.5Fukunaga-Johnson N, Lee JH, Sandler HM, et al.: Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa? Int J Radiat Oncol Biol Phys 42 (1): 143-6, 1998.6Huang 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 52 (3): 599-605, 2002.7Fukunaga-Johnson N, Sandler HM, Marsh R, et al.: The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients with medulloblastoma. Int J Radiat Oncol Biol Phys 41 (1): 77-82, 1998.8Thomas 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 18 (16): 3004-11, 2000.9Ris 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 19 (15): 3470-6, 2001.10Packer 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 24 (25): 4202-8, 2006.11Oyharcabal-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 23 (21): 4726-34, 2005.12Gajjar 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 7 (10): 813-20, 2006.13Packer RJ, Boyett JM, Janss AJ, et al.: Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J Clin Oncol 19 (2): 480-7, 2001.14Packer RJ, Sutton LN, Elterman R, et al.: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 81 (5): 690-8, 1994.15Verlooy 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 42 (17): 3004-14, 2006.16Duffner 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 328 (24): 1725-31, 1993.17Dupuis-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 27 (1): 87-98, 1996.18Rutkowski S, Bode U, Deinlein F, et al.: Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352 (10): 978-86, 2005.19Thorarinsdottir HK, Rood B, Kamani N, et al.: Outcome for children <4 years of age with malignant central nervous system tumors treated with high-dose chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 48 (3): 278-84, 2007.20Grotzer MA, Janss AJ, Fung K, et al.: TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J Clin Oncol 18 (5): 1027-35, 2000.

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Recurrent Childhood Medulloblastoma

Recurrence is not uncommon and may develop many years after initial treatment.[1] Disease may recur at the primary tumor site or by cerebrospinal fluid (CSF) dissemination. Sites of noncontiguous relapse may include the spinal leptomeninges, intracranial sites, and CSF, in isolation, or in any combination, and is variably associated with primary tumor site relapse. Approximately 60% of patients with localized disease at diagnosis will have some component of disseminated disease at relapse, even after 36 Gy of craniospinal radiation therapy.[2] Extraneural disease relapse may occur, but is rare (1% to 2% of relapses), and is primarily reported in patients who were treated with radiation therapy alone.[2] Systemic relapse is rare, but may occur. At time of relapse, a complete evaluation for extent of recurrence is indicated for all malignant tumors and, at times, for more benign lesions. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities such as secondary tumor and treatment-related brain necrosis may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the lesion, and the clinical picture. Patients with recurrent medulloblastoma ,who have already received radiation and chemotherapy, may be candidates for salvage chemotherapy and/or stereotactic irradiation,[3] although long-term disease control is rare.[4][5][6] For select patients, primarily infants and young children who were treated at the time of diagnosis with chemotherapy alone and developed local recurrence, long-term disease control may be obtained after further treatment with high-dose chemotherapy plus local radiation therapy.[7] Entry into studies of novel therapeutic approaches including high-dose chemotherapy and autologous stem cell rescue at the time of relapse after radiation therapy alone or radiation therapy and chemotherapy should be considered.[8][9][10] Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood medulloblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1Jenkin D, Greenberg M, Hoffman H, et al.: Brain tumors in children: long-term survival after radiation treatment. Int J Radiat Oncol Biol Phys 31 (3): 445-51, 1995.2Taylor 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 21 (8): 1581-91, 2003.3Abe M, Tokumaru S, Tabuchi K, et al.: Stereotactic radiation therapy with chemotherapy in the management of recurrent medulloblastomas. Pediatr Neurosurg 42 (2): 81-8, 2006.4Cangir A, van Eys J, Berry DH, et al.: Combination chemotherapy with MOPP in children with recurrent brain tumors. Med Pediatr Oncol 4 (3): 253-61, 1978.5Friedman HS, Oakes WJ: The chemotherapy of posterior fossa tumors in childhood. J Neurooncol 5 (3): 217-29, 1987.6Needle MN, Molloy PT, Geyer JR, et al.: Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. Med Pediatr Oncol 29 (1): 28-32, 1997.7Ridola V, Grill J, Doz F, et al.: High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy. Cancer 110 (1): 156-63, 2007.8Gaynon PS, Ettinger LJ, Baum ES, et al.: Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Cancer 66 (12): 2465-9, 1990.9Gentet JC, Doz F, Bouffet E, et al.: Carboplatin and VP 16 in medulloblastoma: a phase II Study of the French Society of Pediatric Oncology (SFOP). Med Pediatr Oncol 23 (5): 422-7, 1994.10Dunkel 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 16 (1): 222-8, 1998.

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The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

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Changes to This Summary (08/18/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Purpose of This PDQ Summary

Added text about the levels-of-evidence designations that follows some reference citations.

Recurrent Childhood Medulloblastoma

Added text to state that for children who were treated at the time of diagnosis with chemotherapy alone and developed local recurrence, long-term disease control may be obtained after further treatment with high-dose chemotherapy plus local radiation therapy (cited Ridola et. al as reference 7).

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More Information

About PDQ

Additional PDQ Summaries

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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This information was last updated on 2008-08-18