Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®): Treatment - Health Professional Information [NCI]

General Information About Childhood Brain and Spinal Cord Tumors

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. The Central Brain Tumor Registry of the United States (CBTRUS) estimates that approximately 4,300 U.S. children are diagnosed each year.[1]

Brain tumors are classified by histology, but tumor location and extent of spread are also important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of proliferative activity are increasingly used in tumor diagnosis and classification.[2]

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.

References:

1. Ostrom QT, Gittleman H, Farah P, et al.: CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol 15 (Suppl 2): ii1-56, 2013.
2. Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131 (6): 803-20, 2016.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.

General Approach to Care for Children With Brain and Spinal Cord Tumors

Important concepts that should be understood by those treating and caring for a child who has a brain tumor or spinal cord tumor include the following:

1. The cause of most childhood brain tumors remains unknown; however, germline mutations are becoming increasingly recognized as cancer-predisposing, as they are identified in up to 8% of children with cancer.[1,2]
2. Selection of an appropriate therapy can only occur if the correct diagnosis is made and the stage of the disease is accurately determined.
3. Children with primary brain or spinal cord tumors represent a major therapy challenge that, for optimal results, requires the coordinated efforts of pediatric specialists in fields such as neurosurgery, neuropathology, radiation oncology, pediatric oncology, neuro-oncology, neurology, rehabilitation, neuroradiology, endocrinology, and psychology, who have special expertise in the care of patients with these diseases.[3,4] For example, radiation therapy of pediatric brain tumors is technically demanding and should be performed in centers that have experience in this area.
4. For most childhood brain and spinal cord tumors, the optimal treatment regimen has not been determined. Children who have brain and spinal cord tumors should be considered for enrollment in a clinical trial when an appropriate study is available. Such clinical trials are carried out by institutions and cooperative groups. Survival of childhood cancer has increased as a result of clinical trials that have attempted to improve upon the best accepted therapy available. Clinical trials in pediatrics are designed to compare new therapies with treatments that are 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 then comparing the results with those previously obtained using existing therapy. Information about ongoing clinical trials is available from the NCI website.
5. While more than 70% of children diagnosed with brain tumors will survive for more than 5 years after diagnosis, survival rates are wide-ranging depending on tumor type and stage. Long-term sequelae related both to the effects of the tumor and its treatment are common.[5,6,7] Debilitating effects on growth and neurologic development have frequently been observed after radiation therapy, especially in younger children. Secondary tumors have increasingly been diagnosed in long-term survivors.[8] The dose and volume of radiation therapy appropriate for specific tumor types continues to be refined, and techniques for its administration (e.g., more conformal targeted-field design and protons) have evolved to mitigate the potential for adverse effects. In addition, the role of chemotherapy in allowing a delay or reduction in the administration of radiation therapy is under study, and preliminary results suggest that chemotherapy can be used to delay, limit, and sometimes obviate, the need for radiation therapy in children with benign and malignant lesions.[9,10,11] Long-term management of these patients is complex and requires a multidisciplinary approach.

   (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information about possible long-term or late effects.)

6. The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[12]

References:

1. Fisher JL, Schwartzbaum JA, Wrensch M, et al.: Epidemiology of brain tumors. Neurol Clin 25 (4): 867-90, vii, 2007.
2. Zhang J, Walsh MF, Wu G, et al.: Germline Mutations in Predisposition Genes in Pediatric Cancer. N Engl J Med 373 (24): 2336-46, 2015.
3. Parsons DW, Pollack IF, Hass-Kogan DA, et al.: Gliomas, ependymomas, and other nonembryonal tumors of the central nervous system. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 7th ed. Lippincott Williams and Wilkins, 2015, pp 628-70.
4. Pollack IF: Brain tumors in children. N Engl J Med 331 (22): 1500-7, 1994.
5. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
6. Reimers TS, Mortensen EL, Nysom K, et al.: Health-related quality of life in long-term survivors of childhood brain tumors. Pediatr Blood Cancer 53 (6): 1086-91, 2009.
7. Iuvone L, Peruzzi L, Colosimo C, et al.: Pretreatment neuropsychological deficits in children with brain tumors. Neuro Oncol 13 (5): 517-24, 2011.
8. Armstrong GT: Long-term survivors of childhood central nervous system malignancies: the experience of the Childhood Cancer Survivor Study. Eur J Paediatr Neurol 14 (4): 298-303, 2010.
9. 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 328 (24): 1725-31, 1993.
10. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11 (5): 850-6, 1993.
11. Mason WP, Grovas A, Halpern S, et al.: Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. J Clin Oncol 16 (1): 210-21, 1998.
12. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 1, 2022.

Staging, Classification, and Treatment of Newly Diagnosed and Recurrent Childhood Brain and Spinal Cord Tumors

Presently, there is no uniformly accepted staging system for most childhood brain tumors.

The classification of childhood central nervous system (CNS) tumors is based on histology, location, and extent of spread (refer to the Table below).[1] Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of proliferative activity are increasingly used in tumor diagnosis and classification.[1] With advances in molecular data, it is conceivable that genomic factors will refine classification approaches and will be increasingly used to stratify patients entered on clinical trials.

Primary CNS spinal cord tumors comprise approximately 1% to 2% of all childhood CNS tumors. The classification of spinal cord tumors is based on histopathologic characteristics of the tumor and does not differ from that of primary brain tumors.[1]

CNS Tumor Type, Pathologic Subtype, and Its Related PDQ Treatment Summary

Tumor Type (Based on the 2016 WHO Classification)	Pathologic Subtype (Based on the 2016 WHO Classification)	Related PDQ Treatment Summary
CNS = central nervous system; WHO = World Health Organization.
Diffuse astrocytic tumors	Diffuse astrocytoma,IDH-mutant andIDH-wildtype	Childhood Astrocytomas Treatment
	Anaplastic astrocytoma,IDH-mutant andIDH-wildtype
	Glioblastoma,IDH-mutant andIDH-wildtype
	Diffuse midline glioma, H3K27M-mutant	Childhood Astrocytomas Treatment
		Childhood Brain Stem Glioma Treatment
Other astrocytic tumors	Pilocytic astrocytoma	Childhood Astrocytomas Treatment
		Childhood Brain Stem Glioma Treatment
	Subependymal giant cell astrocytoma	Childhood Astrocytomas Treatment
	Pleomorphic xanthoastrocytoma
	Anaplastic pleomorphic xanthoastrocytoma
Ependymal tumors	Subependymoma	Childhood Ependymoma Treatment
	Myxopapillary ependymoma
	Ependymoma
	Ependymoma,RELAfusion–positive
	Anaplastic ependymoma
Other gliomas	Angiocentric glioma	Childhood Astrocytomas Treatment
	Astroblastoma
Neuronal and mixed neuronal-glial tumors	Dysembryoplastic neuroepithelial tumor	Childhood Astrocytomas Treatment
	Ganglioglioma
	Desmoplastic infantile astrocytoma and ganglioglioma
	Papillary glioneuronal tumor
	Rosette-forming glioneuronal tumor
	Diffuse leptomeningeal glioneuronal tumor
	Extraventricular neurocytoma
	Cerebellar liponeurocytoma
	Paraganglioma
Tumors of the pineal region	Pineoblastoma	Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment
Embryonal tumors	Medulloblastoma,WNT-activated	Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment
	Medulloblastoma, SHH-activated andTP53-mutant; Medulloblastoma, SHH-activated andTP53-wildtype
	Medulloblastoma, non-WNT/non-SHH group 3
	Medulloblastoma, non-WNT/non-SHH group 4
	Medulloblastoma, classic
	Medulloblastoma, desmoplastic/nodular
	Medulloblastoma with extensive nodularity
	Medulloblastoma, large cell/anaplastic
	Embryonal tumor with multilayered rosettes,C19MC-altered
	Medulloepithelioma
	CNS neuroblastoma
	CNS ganglioneuroblastoma
	Atypical teratoid/rhabdoid tumor	Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment
	CNS embryonal tumor with rhabdoid features	Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment
Germ cell tumors	Germinoma	Childhood Central Nervous System Germ Cell Tumors Treatment
	Embryonal carcinoma
	Yolk sac tumor
	Choriocarcinoma
	Mature teratoma
	Immature teratoma
	Teratoma with malignant transformation
	Mixed germ cell tumor
Tumors of the sellar region	Adamantinomatous craniopharyngioma	Childhood Craniopharyngioma Treatment
	Papillary craniopharyngioma

Relapse is not uncommon in both low-grade and malignant childhood brain tumors and may occur many years after initial treatment. Disease relapse may occur at the primary tumor site or, especially in malignant tumors, at noncontiguous CNS sites. Systemic relapse is rare but may occur in some tumor types. At recurrence, a complete evaluation for extent of relapse is indicated for all malignant tumors and, at times, for lower-grade lesions. Biopsy or surgical re-resection may be necessary for confirmation of relapse or the diagnosis of tumor transformation, which can include a change in grade and molecular makeup.[2,3] Other entities, such as secondary tumor and treatment-related intratumoral necrosis or frank brain necrosis, may be clinically indistinguishable from tumor recurrence.[4] Determining 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 other clinical parameters.

Early-phase therapeutic trials may be available for selected patients via Children's Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.

References:

1. Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131 (6): 803-20, 2016.
2. Morrissy AS, Garzia L, Shih DJ, et al.: Divergent clonal selection dominates medulloblastoma at recurrence. Nature 529 (7586): 351-7, 2016.
3. Mistry M, Zhukova N, Merico D, et al.: BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J Clin Oncol 33 (9): 1015-22, 2015.
4. Packer RJ, Zhou T, Holmes E, et al.: Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children's Oncology Group trial A9961. Neuro Oncol 15 (1): 97-103, 2013.

Changes to This Summary (10 / 08 / 2021)

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.

General Approach to Care for Children With Brain and Spinal Cord Tumors

Added American Academy of Pediatrics as reference 12.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood brain and spinal cord tumors. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Brain and Spinal Cord Tumors Treatment Overview are:

• Kenneth J. Cohen, MD, MBA (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
• Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)
• Roger J. Packer, MD (Children's National Hospital)
• D. Williams Parsons, MD, PhD
• Malcolm A. Smith, MD, PhD (National Cancer Institute)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

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 Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Brain and Spinal Cord Tumors Treatment Overview. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/brain/hp/child-brain-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389453]

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Last Revised: 2021-10-08