Disease/ Disorder
Definition
Brain tumors include benign and malignant cancers. Most are primary. They are routinely classified based on the histology (glial, embryonal, germ cell tumors, etc.) or the site of origin (supratentorial, infratentorial, meninges, 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, and occurs in advanced rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, or Wilms’ tumor.
Etiology
Etiology is multifactorial and not completely understood.2 Genes regulating cell proliferation and 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 23% 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.
Between 2013 and 2017 in children and adolescents (age 0-19 years), the incidence rate of CNS tumors was 6.14 per 100,000. Incidence was higher in females compared to males and in Caucasians compared to African Americans and Hispanics.1 About 60% of pediatric brain tumors are infratentorial. 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
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.
Patho-anatomy/physiology
Pediatric brain tumors are heterogeneous with diverse biology, histopathological type and grade, growth characteristics, anatomic location, and response to treatment.2 Neuroepithelial tissue gives rise to astrocytic, oligodendroglial, ependymal and choroid plexus tumors. Embryonal tumors include medulloblastoma and central nervous system (CNS) primitive neuroectodermal tumor. Craniopharyngioma arises 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.5
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.2 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. 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.6 Hemiparesis, spasticity and ataxia can ensue. Patients with posterior fossa syndrome presents with diminished or absent speech, hypotonia, ataxia and emotional lability.7 Treatment of tumors may cause complications. Cognitive deficits, behavioral problems, motor, auditory or visual disturbances, and neuropathies may present as late effects of brain tumors.
Essentials of Assessment
History
Deficits at presentation are variable and reflect the area of involvement. Specific questions regarding pain, fatigue, and sleep disturbances should be elicited as these symptoms negative impact therapy participation and quality of life.8 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, reflexes, tone, cranial nerves, speech, vision and hearing should be assessed. A neurocognitive assessment should focus on attention, memory 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 ambulatory aids.9 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 aids in determining social functioning.
Laboratory studies
Complete blood count, blood and urine cultures should be ordered for immunosuppressed patients to rule out infection. Endocrinopathy screen should include vasopressin, thyroid, growth and sex hormones.6 Platelet count should be monitored while undergoing therapy to prevent medical complications from therapy participation (see Translation into Practice, “Pearls” section, below).
Imaging
Suspected tumor recurrence or secondary malignancy should be evaluated with 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.10 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 as 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.7
Environmental
Family functioning (family structure, communication, cohesion, problem solving and emotional expression) has an impact upon the cancer survivor’s psychological well-being.8 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 help other siblings understand the severity of the prognosis. The My Wishes booklet (https://www.agingwithdignity.org/shop/product-details/pediatric-my-wishes) helps begin conversations among parents and children regarding their end of life wishes. The economic burden of cancer can be staggering. Disabilities resulting from cancer diagnoses may make employment difficult.
Rehabilitation Management and Treatments
Available or current treatment guidelines
No specific rehabilitation treatment guidelines are currently available regarding care for children with brain tumors.
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.
Rehabilitation prior to any oncologic treatment to help strengthen any deficits may lead to improvements after treatments. Similar efforts have been instituted in adult based cancer programs to improve a patient’s functional reserve prior to initiating a chemotherapy or radiation program.
The goal of rehabilitation is to maximize function, improve the quality of life, and minimize the caregiver and societal burden.9 Rehabilitation services can support the patient from diagnosis to surgery, adjuvant therapy, survivorship, and terminal or end-of-life care. In the preventive phase, the focuses is on education, strengthening, and conditioning in order to avoid disuse atrophy, maintain or improve strength, endurance, aerobic capacity and bone mineralization. During treatment stage, the rehabilitation aims to restore the functional status. Patients who have significant disabilities and active medical needs (including ongoing chemotherapy and/or radiation) would likely benefits from inpatient rehabilitation. Weakness due to motor strip involvement or neuropathies should 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 setting 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.
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.5 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. Due to the risk of cerebral, intramuscular and joint hemorrhage, 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. Exercise is not recommended when the child has high fever (>40 degree C). Yearly endocrine and neuropsychologic testing is recommended for all CNS tumor patients.5 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, 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 atclinicaltrials.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.
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
- Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017. Neuro Oncol. 2020 Oct 30;22(12 Suppl 2):iv1-iv96.
- 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.
- 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.
- Pollack I. Brain tumors in children. New England Journal of Medicine. 1994;331:1500-1507.
- 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.
- 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.
- 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.
- 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.
- Pruitt DW, Ayyangar R, Craig K, White A, Neufeld JA. Pediatric brain tumor rehabilitation. Journal of pediatric rehabilitation medicine. 2011;4(1):59-70.
- 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.
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
Author Disclosures
Vera Tsetlina, MD
Nothing to Disclose
Hana Azizi, MD
Nothing to Disclose