Author(s): Kimberly C Hartman, MD, MHPE, Susan Li, BA
Originally published: November 17, 2011 Last updated: March 6, 2025
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Disease/Disorder

Definition

Brain tumors include benign and malignant cancers. In the pediatric population, most are primary tumors. They are routinely classified based on the histology (glial, embryonal, germ cell tumors, etc.) or the site of origin (supratentorial, infratentorial, meningeal, etc.). Astrocytoma is the most common pediatric brain tumor overall, while medulloblastoma is the most common malignant brain tumor.1 Metastatic brain tumor is rare in children, but can occur in advanced rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, or Wilms’ tumor.

Etiology

Etiology is multifactorial and not completely understood. Genes regulating cell proliferation and cell death play a critical role. Most gene mutations are somatic (originating within tumor cells), while only a small fraction of children with brain tumor have germline mutations.

Epidemiology including risk factors and primary prevention

Brain tumors account for 25% of all childhood malignancies.2 They are the most common pediatric solid organ cancer, and the leading cause of mortality from childhood cancer, accounting for 25% of all cancer deaths in children. More than 4,000 pediatric brain and spinal cord tumors are diagnosed annually.3

Between 2016 and 2020 in children (age 0-14 years) and adolescents (age 15-19 years), the incidence rate of CNS tumors was 5.44 cases per 100,000 and 7.51 cases per 100,000 in the United States, respectively.2 Incidence was higher in females compared to males and in Caucasians compared to African Americans and Hispanics.1 Supratentorial tumors are more common in the first 2 years of life and late adolescence, while infratentorial tumors predominate in children ages 3-11.4 About 60% of pediatric brain tumors are infratentorial (posterior fossa), with the highest frequency of cases seen in children ages 2 to 5.5

A family history of brain tumors or a family history of genetic syndromes may increase the risk of certain brain tumors. Multiple known cancer predisposition syndromes show associations with brain tumors; for example, Turcot syndrome, DICER1, Li-Fraumeni, and other neurocutaneous syndromes such as neurofibromatosis, tuberous sclerosis, and Von-Hippel Lindau. Exposure to ionizing radiation is one of the few known risk factors for development of primary brain tumors. For example, children who have received radiation for leukemia are known to be at risk for developing brain cancer in the future. Some common gene mutations associated with an increased risk of pediatric brain tumors include TP53, NF1/2 (neurofibromatosis), MLH1, MSH2, MSH6, and PMS2 (DNA mismatch repair), BRAF, and IDH1/2 (gliomas).6

Patho-anatomy/physiology

Pediatric brain tumors are heterogeneous with diverse biology, histopathological type and grade, growth characteristics, anatomic location, and response to treatment. Neuroepithelial tissue gives rise to astrocytic, oligodendroglial, ependymal, and choroid plexus tumors. Embryonal tumors include medulloblastoma and central nervous system (CNS) primitive neuroectodermal tumor. Craniopharyngiomas arise in the sellar region from remnants of Rathke’s pouch. Germ cell tumors arise from embryonic cells located in the midline of the brain.

In 2021, the World Health Organization (WHO) issued 5th revision of the CNS tumor classification (WHO CNS5). In addition to prior principles of diagnosis based on histology and immunohistochemistry, WHO CNS5 incorporates numerous molecular and genetic changes with clinicopathologic utility that are important for the most accurate classification of CNS neoplasms. Perhaps the most significant clinical implications of WHO CNS5 is separating diffuse gliomas into pediatric-type and adult-type. Pediatric type is further classified into pediatric low-grade and pediatric high-grade diffuse gliomas.7

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Initial presentation depends on the site of tumor origin and developmental level of the affected child.8 Initial features are typically nonspecific. Infants and young children may present with irritability, failure to thrive, and developmental delay. Older children may present with fatigue, personality changes, headaches, and declining academic performance. More significant signs and symptoms may include ataxia, hemiparesis, cranial nerve palsy, hyperreflexia, papilledema, seizures, visual or speech disturbances, lethargy, and vomiting. Supratentorial tumors typically manifest with seizures or symptoms related to increased intracranial pressure. Meanwhile, posterior fossa tumors are often associated with headaches, nausea, vomiting, abnormal gait, and coordination difficulties.9 Disease course varies with tumor histology, location, and timely diagnosis. Deaths may be due to disease progression, second malignant tumor, sepsis, cardiovascular disease, or stroke.

Specific secondary or associated conditions and complications

Brain tumors may affect neuroendocrine pathways, resulting in growth retardation, hypothyroidism, or premature or delayed puberty.10 Hemiparesis, spasticity and ataxia can ensue. Patients with posterior fossa syndrome present with diminished or absent speech, hypotonia, ataxia and emotional lability.11 Treatment of tumors may cause complications. Cognitive deficits, behavioral problems, motor, auditory or visual disturbances, and neuropathies may present as late effects of treatment.

Essentials of Assessment

History

Deficits at presentation are variable and reflect the area of involvement. A comprehensive medical history should examine symptoms such as changes in behavior or coordination, headache, nausea or vomiting, seizures, and vision changes. Specific questions regarding pain, fatigue, and sleep disturbances should be elicited, as these symptoms negatively impact therapy participation and quality of life.12 Neck or back pain from poor posture or core muscle weakness is common from prolonged immobility and medical treatments. Assessment of social-emotional functionality, behavioral functioning, access to therapy services and current school attendance is essential.

Physical examination

Sensation, strength, range of motion, coordination, alertness, reflexes, tone, cranial nerves, speech, vision and hearing should be assessed. A neurocognitive assessment should focus on orientation, attention, memory, language, fluency, and processing speed.3 Look for secondary morbidities. Disfigurements, including scars, can affect the child’s self-image. Short stature or precocious puberty may be due to radiation or endocrine effects of the tumor. Obesity may be due to radiation, steroids or endocrine effects of the tumor. Kyphosis or scoliosis may be due to vertebral irradiation.

Functional assessment

Assessment of mobility should include evaluation of overall function, gait, transfers, and need for assistive devices.13 Activities of daily living may be affected by weakness, cognitive impairments, visual changes and ataxia. Cognition, behavior, communication, and mood should be assessed with the assistance of neuropsychologists, occupational therapists and speech therapists. Child life assessments about age-appropriate community interactions aid in determining social functioning.

Laboratory studies

When symptomatic or febrile with a central line, complete blood count, blood and urine cultures should be ordered for immunosuppressed patients to rule out infection. Endocrinopathy screening should include vasopressin, thyroid, growth and sex hormones.10 White blood cell, hemoglobin, and platelet counts should be monitored while undergoing therapy to prevent medical complications from therapy participation (see Translation into Practice, “Pearls” section, below). Brain biopsy is the current gold standard for diagnosing brain tumors that are unresectable and may be required for definitive diagnosis and treatment planning.

Imaging

Depending on acuity of symptoms, brain tumors are usually initially diagnosed after head CT or brain MRI. While computerized tomography scans (CT) are also sometimes used for diagnosis of brain tumors, they pose a risk of increased radiation exposure in children. A previous study found that the risk of brain tumors increases threefold with cumulative radiation doses between 50 and 60 milligray (mGy) to the head.14 For standard CT head settings in children, this would be equivalent to receiving around two to three CT scans. Thus, due to its limited diagnostic value and radiation exposure, CT scans should only be used in emergency settings or when MRI acquisition is not obtainable.

Suspected tumor recurrence or secondary malignancy should be evaluated with the current diagnostic gold standard, magnetic resonance imaging (MRI), with and without contrast. Young children may require sedation. Functional MRI may be used to assess tumor’s impact on language and motor centers. Activity on positron-emission tomography (PET) scan may help detect early tumor recurrence, guide biopsy and optimize tumor resection.15 Musculoskeletal complaints require lower thresholds to obtain imaging studies given high risk of metastatic disease, osteomyelitis, osteopenia, and avascular necrosis.

Supplemental assessment tools

Many neuropsychological assessment tools exist. The Working Memory Index and the Processing Speed Index are helpful components of the Wechsler Adult Intelligence Scale. The Trail Making Test and the Behavior Rating Inventory of Executive Function (BRIEF) assess executive functioning. Brief versions of neuropsychological tests, such as the Digit Span portion of the Working Memory Index and the BRIEF, enable quick screens in the office. Fatigue can be assessed with the Peds-QL multidimensional fatigue scale.

Early predictions of outcomes

Patients with hemispheric tumors and those with recurrence or those who require additional surgery tend to have greater impairments and worse physical functioning. Poor prognosis is associated with younger age, radiation treatment, hydrocephalus requiring ventriculoperitoneal shunting, and aggressive histologic tumor type. Moreover, radiation treatment is associated with adverse endocrine outcomes and poor cognitive outcomes, low intelligence quotient (IQ) and lower rates of employment and marriage.11 The Neurological Predictor Scale (NPS) is a tool used primarily in clinical settings to evaluate and predict neurological outcomes based on various indicators such as clinical symptoms, imaging results, functional status, and medical history. It assesses factors such as tumor size, location, and the extent of neurological symptoms to predict neurological outcomes in cognitive and motor functions. The cumulative score helps clinicians make informed decisions about surgery, radiation therapy, or other treatments.16

Environmental

Family functioning (family structure, communication, cohesion, problem solving and emotional expression) has an impact upon the cancer survivor’s psychological well-being.12 Questionnaires that assess family functioning include the Family Assessment Device and the Family Environment Scale.

Social role and social support system

A 504 plan or individualized education plan (IEP) may be required to create school accommodations. Assess the caregiver and family burden, including stress, fatigue, occupational effects and financial burden. Support groups can be critical to minimizing stress for patients and families to discuss shared experiences.

Professional issues

If prognosis is terminal, early discussions regarding end-of-life care should take place in conjunction with a palliative care team. Child Life Specialists can help other siblings understand the severity of the prognosis. The Five Wishes booklet (https://store.fivewishes.org/ShopLocal/en/p/MW-MASTER-000/my-wishes) helps begin conversations among parents and children regarding their end of life wishes. The economic burden of cancer can be staggering, and disabilities resulting from cancer diagnoses may make employment difficult.

Rehabilitation Management and Treatments

Available or current treatment guidelines

In 2023, the National Comprehensive Cancer Network (NCCN) issued new guidelines for pediatric CNS cancers which emphasize a comprehensive approach to diagnosis, treatment, and long-term management. The NCCN recommends detailed initial evaluations, including neuroimaging and biopsies, and provides updated staging criteria. Treatment protocols include precise guidelines for surgery, radiation, and chemotherapy, tailored to minimize harm and enhance effectiveness. The guidelines also stress the importance of long-term monitoring, rehabilitation, and a multidisciplinary care team, while encouraging participation in clinical trials to advance research and treatment options.17

At different disease stages

Management requires a multimodal approach. Depending on the histology of the tumor, surgery, radiotherapy, and chemotherapy may be required. Total gross tumor resection may not be possible due to the risk of causing permanent and devastating neurologic deficits. Supportive care and monitoring for late effects of cancer and its therapy, including neurological, endocrine, skeletal and soft tissue sequelae, are of paramount importance.

The goals of rehabilitation are to maximize function, improve the quality of life, and to minimize caregiver and societal burden.13 Rehabilitation services can support the patient through all stages – from diagnosis to surgery, adjuvant therapy, survivorship, and terminal or end-of-life care. The Dietz Classification of Cancer Rehabilitation is a commonly used model to describe goals of rehabilitative care throughout the cancer continuum.18

  • Preventative Rehabilitation (Prehabilitation): early intervention and exercise to identify impairments and prevent or delay complications
  • Restorative Rehabilitation: targeted therapy to alleviate functional impairments and restore function
  • Supportive Rehabilitation: interventions to optimize function for those who experience disability after cancer treatments
  • Palliative Rehabilitation: interventions aimed at maintaining function, maximizing comfort, and maximizing quality of life

In the preventive phase, the focus is on education, strengthening, and conditioning in order to avoid disuse atrophy, to maintain or improve strength, and to increase endurance, aerobic capacity and bone mineralization. During treatment stage, the rehabilitation aims to restore the patient’s functional status. Patients who have significant disabilities and active medical needs (including ongoing chemotherapy and/or radiation) would likely benefit from inpatient rehabilitation. Weakness due to motor strip involvement or neuropathies should also be addressed. Gait aids are prescribed to improve mobility and ambulation safety. During surveillance stage, the focus is again on conditioning, strengthening, and resistance training. Sensation and proprioception should be assessed. Optimal vocational and educational settings should be provided. During terminal or palliative stage, the goal of rehabilitation is symptom control and caregiver education. Additional assistive devices and durable medical equipment may be needed.

The Children’s Oncology Group (COG) Long-Term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers is a comprehensive resource for monitoring for late effects of different tumors and treatments.  The resource is updated regularly and should be utilized by a multidisciplinary team to screen for and minimize late effects of cancer on function and quality of life.19

Coordination of care

An interdisciplinary approach is necessary, and the physicians on such a team should consist of pediatric tumor experts – including pediatric physiatrists, neurosurgeons, neurologists, neuro-pathologists, neuro-radiologists, neuro-oncologists, radiation oncologists, ophthalmologists, neuropsychologists, and pharmacologists.7 This collaboration may occur during multidisciplinary tumor board meetings, multidisciplinary clinical settings, or through carefully coordinated consultations. The team should also include nurses, social workers, audiologists, nutritionists, child life specialists, and physical, occupational and speech therapists.

Patient & family education

Psychological counseling and support should be provided to the patient, parents, and siblings. Many support groups are available worldwide. Pediatric Brain Tumor Foundation (www.curethekids.org) has multiple educational materials, which are accessible to patients and their families at no charge.

Emerging/unique interventions

There are no objective measurements of functional assessments designed specifically for pediatric brain tumor survivors. The Childhood Orientation and Amnesia Test, designed to assess cognitive function after acquired brain injury, is frequently used. WeeFIM or Pediatric Evaluation of Disability Inventory (PEDI) can be used to assess functional performance. The Health-Related Quality of Life assessments, such as PedsQL, is frequently used.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

The rehabilitation goals need to be individualized, realistic and dynamic. The plan should be implemented early and tailored to meet the goals of the patient and the family. Depending on the child’s medical status, the intensity and type of exercise may have to be adjusted.

Based on findings of past studies, due to the risk of cerebral, intramuscular, and joint hemorrhage, typically no significant exercise is recommended if platelet count is less than 20,000/microliter; gentle bedside exercise excluding passive range of motion if platelets are between 20,000/microliter and 30,000/microliter; active exercise without resistance can be performed if platelets are between 30,000/microliter and 50,000/microliter. However, more recent studies have found no significant association between physiotherapy and severe exercise-related bleeding in patients with platelet count < 20,000/microliter.20 Nonetheless, caution should be taken and duration and frequency of resistance exercises should be adaptable to prevent bleeding. Patients should start with low-resistance exercises and be carefully monitored for bleeding events before increasing exercise intensity.

Extra precautions may be required in children with neutropenia to prevent infection. Exercise is not recommended when the child has high fever (>40 degree C). In children with significant anemia, the therapy plan should be adjusted to accommodate for symptoms of fatigue and the potential for decreased exercise tolerance.  Transfusion thresholds can vary but earlier transfusion may be considered if the child has poor tolerance to rehabilitative interventions.

Yearly endocrine and neuropsychologic testing is recommended for all patients with CNS tumor.7 If the tumor resection surgery is likely to affect speech, then voice banking for an augmentative communication device should be considered. Any patient at risk for aspiration should undergo formal swallowing evaluation. Weight should be monitored closely. Pain should be addressed frequently and managed effectively. Ultrasound and heat modalities are avoided in proximity to the tumor or in diffuse metastatic disease. Methylphenidate and amantadine can be tried to help improve concentration and fatigue, respectively. Spasticity, especially in acute stages, is best managed with local chemodenervation (i.e., botulinum toxin injections), as systemic medications cause sedation and may affect long-term cognitive outcome.

Cutting Edge/Emerging and Unique Concepts and Practice

The U.S. National Institute of Health database of currently ongoing clinical trials can be viewed at clinicaltrials.gov. The use of adjuvant chemotherapy has reduced the doses of craniospinal radiotherapy administered. Proton radiation therapy is being used more frequently. Physical properties of proton therapy allow delivering high dose radiation to a very precise brain lesion while minimizing damage to surrounding normal tissues. Current studies explore the efficacy of administering concurrent chemotherapy and radiotherapy, and treatment with high-dose chemotherapy with autologous hematopoietic stem cell reconstitution. Other promising studies focus on inhibition of angiogenesis, disruption of growth factor-mediated signaling, intrathecal chemotherapy, and local delivery of chemotherapy or molecularly targeted agents to the tumor site.

In 2024, the Food and Drug Administration (FDA) approved a combination Tafinlar and Mekinist drug as a first-line option for children with low-grade gliomas (LGGs) with a BRAF V600E mutation. LGGs are the most prevalent type of brain cancer in children, and those with the BRAF V600 mutation often face poorer survival rates due to a decreased response to chemotherapy (the current standard of care). Since there is also a liquid version available, children as young as one year of age will be able to take the medication. There are other medications available that target various gene mutations and proteins such as IDH1/2 and MEK1/2. A significant limitation of targeted therapy for brain tumors, however, is the challenge of the blood-brain barrier. Overcoming this protective barrier is a critical consideration for improving the efficacy of targeted therapies in treating brain tumors. The potential of immunotherapies including CAR-T cell therapy is also actively being studied.9

Gaps in the Evidence-Based Knowledge

Identifying the causes of somatic mutations and characterization of genetic abnormalities associated with pediatric brain tumors may have therapeutic implications. Even more refined surgical approaches and intraoperative modalities are needed for safer and more efficient tumor resection.

With new developments in neuro-oncology treatments, the role of rehabilitation should continue to expand to minimize disability and maximize quality of life. Quality of life should be considered as a secondary outcome in all the pediatric cancer treatment protocols. Rehabilitation medicine is most equipped in determining the disability measures and quality of life indicators and should be a part of the discussion.

References

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  2. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024.
  3. Hocking MC, Hobbie WL, Deatrick JA, et al. Neurocognitive and family functioning and quality of life among young adult survivors of childhood brain tumors. The Clinical neuropsychologist. Aug 2011;25(6):942-962.
  4. Koob M, Girard N. Cerebral tumors: specific features in children. Diagn Interv Imaging. 2014 Oct;95(10):965-83. doi: 10.1016/j.diii.2014.06.017. Epub 2014 Aug 20. PMID: 25150727.
  5. Kornienko, V. N., & Pronin, I. N. (2009). Diagnostic Neuroradiology (2009th ed.). Springer.
  6. Farouk Sait S, Walsh MF, Karajannis MA. Genetic syndromes predisposing to pediatric brain tumors. Neurooncol Pract. 2021 Feb 13;8(4):375-390. doi: 10.1093/nop/npab012. PMID: 34277017; PMCID: PMC8278355.
  7. Louis DN, Perry A, Wesseling P et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary, Neuro-Oncology, Aug 2021;23 (8):1231–1251.
  8. Blaney S, Kun L, Hunter J. Tumors of the Central Nervous System. In: Pizzo P, Poplack D, eds. Principles and Practices of Pediatric Oncology. Vol 5th. New York, NY: Lippincott, Williams, and Wilkins; 2006.
  9. Kulubya ES, Kercher MJ, Phillips HW, Antony R, Edwards MSB. Advances in the Treatment of Pediatric Brain Tumors. Children (Basel). 2022 Dec 27;10(1):62. doi: 10.3390/children10010062. PMID: 36670613; PMCID: PMC9856380.
  10. Turner CD, Rey-Casserly C, Liptak CC, Chordas C. Late effects of therapy for pediatric brain tumor survivors. Journal of child neurology. Nov 2009;24(11):1455-1463.
  11. Pollack IF, Polinko P, Albright AL, Towbin R, Fitz C. Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology. Neurosurgery. Nov 1995;37(5):885-893.
  12. Sands SA, Pasichow KP, Weiss R, et al. Quality of life and behavioral follow-up study of Head Start I pediatric brain tumor survivors. Journal of neuro-oncology. Jan 2011;101(2):287-295.
  13. Pruitt DW, Ayyangar R, Craig K, White A, Neufeld JA. Pediatric brain tumor rehabilitation. Journal of pediatric rehabilitation medicine. 2011;4(1):59-70.
  14. Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, Howe NL, Ronckers CM, Rajaraman P, Sir Craft AW, Parker L, Berrington de González A. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet. 2012 Aug 4;380(9840):499-505. doi: 10.1016/S0140-6736(12)60815-0. Epub 2012 Jun 7. PMID: 22681860; PMCID: PMC3418594.
  15. Pirotte B, Acerbi F, Lubansu A, Goldman S, Brotchi J, Levivier M. PET imaging in the surgical management of pediatric brain tumors. Child’s nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. Jul 2007;23(7):739-751.
  16. Srsich AR, McCurdy MD, Fantozzi PM, Hocking MC. Predicting neuropsychological late effects in pediatric brain tumor survivors using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity. Journal of the International Neuropsychological Society. 2024;30(4):380-388. doi:10.1017/S1355617723000589
  17. NCCN Guidelines Insights: Central Nervous System Cancers, Version 2.2022: J Natl Compr Canc Netw. 2023 Jan;21(1):12-20. doi: 10.6004/jnccn.2023.0002
  18. Chowdhury RA, Brennan FP, Gardiner MD. Cancer Rehabilitation and Palliative Care-Exploring the Synergies. J Pain Symptom Manage. 2020 Dec;60(6):1239-1252. doi: 10.1016/j.jpainsymman.2020.07.030. Epub 2020 Aug 6. PMID: 32768554; PMCID: PMC7406418.
  19. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers, Version 6.0. Monrovia, CA: Children’s Oncology Group; October 2023; Available on-line: www.survivorshipguidelines.org.
  20. Morishita, S., Nakano, J., Fu, J. B., & Tsuji, T. (2020). Physical exercise is safe and feasible in thrombocytopenic patients with hematologic malignancies: a narrative review. Hematology, 25(1), 95–100. https://doi.org/10.1080/16078454.2020.1730556

Original Version of the Topic

Kasia Ibanez, MD, Eric Wisotzky, MD. Pediatric Brain Tumor. Publication Date: 11/17/2011

Previous Revision(s) of the Topic

Matthew McLaughlin, MD. Pediatric Brain Tumor. 8/19/2016

Vera Tsetlina, MD, Hana Azizi, MD. Pediatric Brain Tumor. 9/23/2021

Author Disclosures

Kimberly C Hartman, MD, MHPE
Nothing to Disclose

Susan Li, BA
Nothing to Disclose