General Information

Cellular Classification

Stage Information

Treatment Option Overview

Untreated Childhood Medulloblastoma

Recurrent Childhood Medulloblastoma

The National Cancer Institute (NCI) has updated its cancer information delivery services. In the future, please use the Cancer.gov web site (Http: //cancer.gov/) to meet your cancer information needs. CancerMail users in the United States can obtain cancer information by telephone at 1-800-4-CANCER (1-800-422-6237).

The NCI will no longer support CancerMail after November 2002. If you have comments about the NCI's cancer information delivery services, contact us by e-mail at cancer.govstaff@mail.nih.gov or call 301-496-9096.

###########################################################################

GENERAL INFORMATION

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.

Approximately 50% of brain tumors in children are infratentorial, with three fourths of these located in the cerebellum or fourth ventricle. Common infratentorial (posterior fossa) tumors include the following:

1. cerebellar astrocytoma (usually pilocytic but also fibrillary and
high-grade)

2. medulloblastoma (primitive neuroectodermal tumor)

3. ependymoma (low-grade or anaplastic)

4. brain stem glioma (often diagnosed neuroradiographically without biopsy;
may be high-grade or low-grade)

5. atypical teratoid

Supratentorial tumors include those tumors that occur in the sellar or suprasellar region and/or other areas of the cerebrum. Sellar/suprasellar tumors comprise approximately 20% of childhood brain tumors and include the following:

1. craniopharyngioma

2. diencephalic (chiasm, hypothalamic, and/or thalamic) gliomas generally of
low grade

3. germ cell tumors (germinoma and nongerminomatous)

Other tumors that occur supratentorially include the following:

1. low-grade astrocytoma or glioma (grade 1 or grade 2)

2. high-grade or malignant astrocytoma (anaplastic astrocytomas, glioblastomas
multiforme (grade 3 or grade 4))

3. mixed glioma (low-grade or high-grade)

4. oligodendroglioma (low-grade or high-grade)

5. primitive neuroectodermal tumor (cerebral neuroblastoma)

6. ependymoma (low-grade or anaplastic)

7. meningioma

8. choroid plexus tumors (papilloma and carcinoma)

9. pineal parenchymal tumors (pineoblastoma, pineocytoma, or mixed pineal
parenchymal tumor)

10. neuronal and mixed neuronal glial tumor (ganglioglioma, desmoplastic
infantile ganglioglioma, dysembryoplastic neuroepithelial tumor)

11. metastasis (rare) from extra neural malignancies

Important general concepts that should be understood by those caring for a child with brain tumor include the following:

1. Selection of an appropriate therapy can only occur if the correct diagnosis
is made and the stage of the disease is accurately determined.

2. Children with primary brain tumors represent a major therapy challenge that,
for optimal results, requires the coordinated efforts of pediatric specialists in fields such as neurosurgery, neurology, rehabilitation, neuropathology, radiation oncology, medical oncology, neuroradiology, endocrinology, and psychology, who have special expertise in the care of patients with these diseases.[1-3]

3. More than one half of children diagnosed with brain tumors will survive
5 years from diagnosis. In some subgroups of patients, an even higher rate of survival and cure is possible. Each child's treatment should be approached with curative intent, and the possible long-term sequela of the disease and its treatment should be considered before therapy is begun.

4. For the majority of childhood brain tumors, the optimal treatment regimen
has not been determined. Children who have brain tumors should be considered for enrollment in clinical trials when an appropriate study is available. Such clinical trials are being carried out by institutions and cooperative groups.

5. Guidelines for pediatric cancer centers and their role in the treatment of
pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[4]

6. The cause of the vast majority of childhood brain tumors remains
unknown.[5,6]

This summary discusses the treatment of childhood medulloblastoma, the single most common malignant childhood brain tumor.

Information about ongoing clinical trials is available from the NCI (Http: //cancer.gov/clinical_trials/).

References:

1. Heideman RL, Packer RJ, Albright LA, et al.: Tumors of the central nervous system. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. Philadelphia, Pa: Lippincott-Raven, 3rd ed., 1997, pp 633-697.
2. Pollack IF: Brain tumors in children. New England Journal of Medicine 331(22): 1500-1507, 1994.
3. Cohen ME, Duffman PK, eds: Brain Tumors in Children: Principles of Diagnosis and Treatment, 2nd ed. New York: Raven Press, 1994.
4. Sanders J, Glader B, Cairo M, et al.: Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99(1): 139-141, 1997.
5. Kuijten RR, Bunin GR: Risk factors for childhood brain tumors. Cancer Epidemiology, Biomarkers and Prevention 2(3): 277-288, 1993.
6. Kuijten RR, Strom SS, Rorke LB, et al.: Family history of cancer and seizures in young children with brain tumors: a report from the Childrens Cancer Group (United States and Canada). Cancer Causes and Control 4(5): 455-464, 1993.

CELLULAR CLASSIFICATION

References:

1. Russo C, Pellarin M, Tingby O, et al.: Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors. Cancer 86(2): 331-339, 1999.
2. Nicholson JC, Ross FM, Kohler JA, et al.: Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours. British Journal of Cancer 80(9): 1322-1331, 1999.
3. Rorke LB: The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. Journal of Neuropathology and Experimental Neurology 42(1): 1-15, 1983.
4. Gilles FH: Classification of childhood brain tumors. Cancer 56(7, Suppl): 1850-1857, 1985.
5. Dehner LP: Peripheral and central primitive neuroectodermal tumors: a nosologic concept seeking a consensus. Archives of Pathology and Laboratory Medicine 110(11): 997-1005, 1986.
6. Rorke LB, Gilles FH, Davis RL, et al.: Revision of the World Health Organization classification of brain tumors for childhood brain tumors. Cancer 56(7, Suppl): 1869-1886, 1985.
7. Burger PC, Scheithauer BW: Tumors of the central nervous system. Washington DC: Armed Forces Institute of Pathology. 1994.

STAGE INFORMATION

Medulloblastoma

Average risk - Children older than 3 years of age with posterior fossa tumors; tumor is totally or "near-totally" (<1.5 cubic centimeters of residual disease) resected; no dissemination.[3]

Poor risk - Children younger than 3 years of age or those with metastatic disease and/or subtotal resection (>1.5 cubic centimeters of residual disease) and/or nonposterior fossa location.[3]

References:

1. Fouladi 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. Journal of Clinical Oncology 17(10): 3234-3237, 1999.
2. 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 38(2): 265-271, 1996.
3. Laurent JP, Chang CH, Cohen ME: A classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. Cancer 56(7, Suppl): 1807-1809, 1985.
4. Packer RJ, Siegel KR, Sutton LN, et al.: Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Annals of Neurology 24(4): 503-508, 1988.
5. Zerbini C, Gelber RD, Weinberg D, et al.: Prognostic factors in medulloblastoma, including DNA ploidy. Journal of Clinical Oncology 11(4): 616-622, 1993.
6. Schofield DE, Yunis EJ, Geyer JR, et al.: DNA content and other prognostic features in childhood medulloblastoma: proposal of a scoring system. Cancer 69(5): 1307-1314, 1992.
7. Tomita T, Yasue M, Engelhard HH, et al.: Flow cytometric DNA analysis of medulloblastoma: prognostic implication of aneuploidy. Cancer 61(4): 744-749, 1988.
8. Gajjar AJ, Heideman RL, Douglass EC, et al.: Relation of tumor-cell ploidy to survival in children with medulloblastoma. Journal of Clinical Oncology 11(11): 2211-2217, 1993.
9. Grotzer MA, Janss AJ, Fung K, et al.: TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. Journal of Clinical Oncology 18(5): 1027-1035, 2000.
10. Grotzer MA, Hogarty MD, Janss AJ, et al.: MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma. Clinical Cancer Research 7(8): 2425-2433, 2001.
11. Gilbertson RJ, Perry RH, Kelly PJ, et al.: Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Research 57(15): 3272-3280, 1997.

TREATMENT OPTION OVERVIEW

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. Radiation therapy of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in that area in order to ensure optimal results. Less than optimal techniques have resulted in failure at the junction of the brain and spine 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 recurrent medulloblastomas. Prospective, randomized trials and large single-arm trials suggest that adjuvant chemotherapy given during and after radiation therapy may improve overall survival for the subset of children with medulloblastoma who have less favorable prognostic factors, and there has been enthusiasm for exploring the role of chemotherapy in the treatment of childhood brain tumors.[2-4] Children younger than 3 years of age 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.[5,6] 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.[2,7] Surveillance testing is presently a part of all ongoing medulloblastoma studies.[8] Secondary tumors have increasingly been diagnosed in long-term survivors.[9,10] 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.

References:

1. 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). International Journal of Radiation Oncology, Biology, Physics 45(2): 435-439, 1999.
2. 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. New England Journal of Medicine 328(24): 1725-1731, 1993.
3. Ater JL, van Eys J, Woo SY, et al.: MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children. Journal of Neuro-Oncology 32(3): 243-252, 1997.
4. Packer RJ, Sutton LN, Elterman R, et al.: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. Journal of Neurosurgery 81(5): 690-698, 1994.
5. 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. Journal of Neurosurgery 70(5): 707-713, 1989.
6. Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term survival in young children with medulloblastoma. Journal of Neurosurgery 80(6): 1004-1010, 1994.
7. Mason WP, Grovas A, Halpern S, et al.: Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. Journal of Clinical Oncology 16(1): 210-221, 1998.
8. Torres CF, Rebsamen S, Silber JH, et al.: Surveillance scanning of children with medulloblastoma. New England Journal of Medicine 330(13): 892-895, 1994.
9. Jenkin D: Long-term survival of children with brain tumors. Oncology (Huntington NY) 10(5): 715-719, (discussion 720, 722, 728), 1996.
10. Goldstein AM, Yuen J, Tucker MA: Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes and Control 8(6): 865-871, 1997.

UNTREATED CHILDHOOD MEDULLOBLASTOMA

Treatment options:[3]

Average risk:

The traditional postsurgical treatment for these patients has been radiation therapy consisting of 5,400 to 5,580 cGy to the posterior fossa and approximately 3,600 cGy 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 might be equally effective,[4] yet associated with reduced toxicity.[5,6] The minimal dose of radiation therapy needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 2,340 cGy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[7] Radiation therapy, 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.[8,9] 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.[10] Consult PDQ for information on clinical trials.

Poor risk:

In poor-risk patients, the addition of chemotherapy has improved the duration of disease-free survival.[11] Some studies show that approximately 50% to 60% of such patients will experience long-term disease control.[2] These are patients who, at diagnosis, have locally extensive and often unresectable tumor in the posterior fossa, brain stem involvement at diagnosis, and/or noncontiguous metastatic disease within or outside of the central nervous system. Adjuvant chemotherapy has improved progression-free survival for patients with these "poor-risk" parameters at diagnosis.[2,11] Such patients should be considered for entry into a clinical trial.[2,3] 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.[10] Consult PDQ for information on current clinical trials.

Children younger than 3 years of age:

Some patients younger than 3 years of age with newly diagnosed medulloblastoma will respond, at least partially, to chemotherapy.[12] Some patients, especially those with minimal residual postoperative disease, may have a long-lasting response.[3,12] Those children treated with chemotherapy alone may have better neurocognitive outcome than those treated with radiation therapy, with or without chemotherapy.[13] For this reason, strong consideration should be given to entering patients younger than 3 years of age in studies that use chemotherapy to delay, modify, or possibly obviate the need for radiation therapy.[12] High-dose chemotherapy with autologous bone marrow rescue followed by focal radiation therapy has been used with some success in young children with locally recurrent disease for whom primary chemotherapy has failed. Although chemotherapy is being used to prevent neurologic damage caused by radiation therapy in very young patients, neurologic deficits may be present in children prior to the initiation of therapy, and progressive neurologic damage has been noted during therapy.[14]

References:

1. 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 38(2): 265-271, 1996.
2. 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. Journal of Neurosurgery 72(4): 572-582, 1990.
3. 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 Children Cancer Group. Journal of Clinical Oncology 12(8): 1607-1615, 1994.
4. Fukunaga-Johnson N, Lee JH, Sandler HM, et al.: Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa? International Journal of Radiation Oncology, Biology, Physics 42(1): 143-146, 1998.
5. Huang E, Teh BS, Strother DR, et al.: Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. International Journal of Radiation Oncology, Biology, Physics 52(3): 599-605, 2002.
6. Fukunaga-Johnson N, Sandler HM, Marsh R, et al.: The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients with medulloblastoma. International Journal of Radiation Oncology, Biology, Physics 41(1): 77-82, 1998.
7. Thomas PR, Deutsch M, Kepner JL, et al.: Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. Journal of Clinical Oncology 18(16): 3004-3011, 2000.
8. 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. Journal of Clinical Oncology 19(15): 3470-3476, 2001.
9. 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. Journal of Clinical Oncology 17(7): 2127-2136, 1999.
10. Packer RJ, Boyett JM, Janss AJ, et al.: Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. Journal of Clinical Oncology 19(2): 480-487, 2001.
11. Packer RJ, Sutton LN, Elterman R, et al.: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. Journal of Neurosurgery 81(5): 690-698, 1994.
12. 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. New England Journal of Medicine 328(24): 1725-1731, 1993.
13. Copeland DR, deMoor C, Moore BD III, et al.: Neurocognitive development of children after a cerebellar tumor in infancy: a longitudinal study. Journal of Clinical Oncology 17(11): 3476-3486, 1999.
14. Mulhern RK, Horowitz ME, Kovnar EH, et al.: Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy. Journal of Clinical Oncology 7(11): 1660-1666, 1989.

RECURRENT CHILDHOOD MEDULLOBLASTOMA

References:

1. Jenkin D, Greenberg M, Hoffman H, et al.: Brain tumors in children: long-term survival after radiation treatment. International Journal of Radiation Oncology, Biology, Physics 31(3): 445-451, 1995.
2. Cangir A, Van Eys J, Berry DH, et al.: Combination chemotherapy with MOPP in children with recurrent brain tumors. Medical and Pediatric Oncology 4(3): 253-261, 1978.
3. Friedman HS, Oakes WJ: The chemotherapy of posterior fossa tumors in childhood. Journal of Neuro-Oncology 5(3): 217-229, 1987.
4. Needle MN, Molloy PT, Geyer JR, et al.: Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. Medical and Pediatric Oncology 29(1): 28-32, 1997.
5. Gaynon PS, Ettinger LJ, Baum ES, et al.: Carboplatin in childhood brain tumors: a Children's Cancer Study Group phase II trial. Cancer 66(12): 2465-2469, 1990.
6. Gentet 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). Medical and Pediatric Oncology 23(5): 422-427, 1994.
7. Dunkel IJ, Boyett JM, et al, for the Children's Cancer Group: High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Journal of Clinical Oncology 16(1): 222-228, 1998.

Browse and Submit Oncology Conferences

Sponsors: Health on the Net Foundation (Geneva) Landesregierung NRW (im Rahmen von HSP III) FAST Multimedia AG  Schnittpunkt

<A HREF ="deutsch/CancernetDSL.ram">Play clip using the stand-alone RealPlayer!</A><A HREF ="http://www.real.com/products/player/d1.html">Click here to download the latest RealPlayer!</A> small video clip about our work (200 Kbit/s)

Back to the Cancernet contents overview Questions? Mail them to us!

We subscribe to the HONcode principles of the Health On the Net Foundation

This page was last modified on Sunday, 02-Nov-2003 15:45:21 CET