Childhood Astrocytomas

Introduction:

  • Brain tumors are the most common solid tumors found in children and the second most common cancer overall in childhood behind leukemia. 
  • The focus of this topic will be on childhood astrocytomas, which account for approximately 30-40% of all pediatric brain tumors.
  • Astrocytomas, neoplasms originating from astrocytes, belong to a larger group of glial-derived tumors called gliomas, which also include:
    • oligodendrogliomas
    • ependymomas
    • brain stem gliomas
    • mixed gliomas (e.g. oligoastrocytomas).

 

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Figure by Ramin Morshed

  • Astrocytomas may be low-grade (e.g. pilocytic astrocytoma and diffuse astrocytoma) or high-grade (e.g. anaplastic astrocytoma, glioblastoma, and diffuse intrinsic pontine glioma).
    • Grade I pilocytic astrocytomas:
      • are the most common in children age 0-14      
      • account for 17.6% of all brain tumors.

 

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Pilocytic Astrocytoma – Image from Radiopaedia.org

http://images.radiopaedia.org/images/25692/371b55cc149120b9cc64dd4f6febff.jpg

Etiology:

  • The etiology of sporadic astrocytomas in children is not understood
  • There are familial syndromes associated with astrocytomas such as:
    • Neurofibromatosis-1 and 2
    • Tuberous sclerosis
    • Turcot syndrome
    • Li-Fraumeni syndrome
  • There have been no consistent links to any environmental exposures or parental occupational exposures.
  • Prior radiation to the cranium for other malignancies may account for some secondary supratentorial astrocytomas
  • Certain conditions are associated with specific astrocytoma subtypes:
    • Neurofibromatosis-1 can be associated with optic nerve gliomas.
    • Tuberous sclerosis can be associated with a type of low-grade astrocytoma known as subependymal giant cell astrocytoma.

 

Epidemiology:

  • The incidence of astrocytomas in ages 0-14 is roughly 1.75 per 100,000
  • Astrocytomas can occur at any age of childhood, but the highest incidence occurs between the ages of 1-4.
  • The male-to-female ratio is roughly 1:1
  • There is no apparent racial predisposition

 

Symptoms:

  • Astrocytomas may present in a similar manner to other forms of brain cancer such as medulloblastomas or ependymomas.
  • Symptoms are usually due to:
    • Increased intracranial pressure (ICP)
    • Mass effect
    • Disruption of functional circuitry in a particular location in the CNS.
  • History and physical exam may reveal:
    • Seizures
    • Headaches that are worse in the morning or when lying down
    • Recurrent vomiting
    • Cranial nerve palsies (due to herniation)
    • Incoordination/ataxia
    • Behavioral changes
    • Weakness or sensory changes
    • Loss of vision
    • Short stature
    • Hydrocephalus
  • Of note, just because a tumor is “benign” (i.e. low-grade), this does not mean that the clinical course is benign.
    • These tumors can still lead to increased ICP, though the clinical course will usually progress more gradually than high-grade malignancies.
  • Clinicians should always be on the lookout for signs of increased ICP, as this may eventually lead to vascular compromise, tissue ischemia, or even brain herniation, culminating in death.

 

Imaging and Diagnosis:

  • Initial evaluation may consist of a head CT for the presence of symptoms indicative of an intracranial mass.
  • If a mass is seen, head CT is usually followed by a MRI of the head with and without contrast.
  • Imaging may reveal vasogenic edema surrounding the tumor.
  • Low-grade tumors tend to be non-enhancing on MRI with less evidence of surrounding edema.
  • Hydrocephalus may be present if ventricular outflow is obstructed.  
  • Other features may include:
    • Intratumor calcifications
    • Cystic components (e.g. pilocytic astrocytoma)
    • Necrosis
    • Midline shift
    • Brain tissue herniation
    • Distant tissue ischemia secondary to vascular compromise.
  • While imaging studies may be highly suggestive of a brain neoplasm, diagnosis is usually confirmed at the time of surgical resection upon histological examination of resected tissue.
  • Serial MRIs are also done after surgery to assess for resection extent and, as time goes on, for tumor recurrence. This information can be used to guide further treatment regimens.

 

Treatment:

  • The general treatment of astrocytomas depends on the tumor grade and its location.
  • Low-grade astrocytomas may be treated with surgical resection alone, leading to a 10-year survival rates as high as 90% (Claus et al. 2006).
  • If the tumor is in an inoperable location (i.e. the brain stem), radiotherapy to the area or chemotherapy agents like vincristine and carboplatin may be used.
  • While prognosis for low-grade tumors is good overall, it must be noted that these patients can suffer from long-term complications such as intellectual impairment (Armstrong et al. 2011).
  • High-grade astrocytomas have poor prognosis despite surgical resection, radiotherapy, and chemotherapy.
  • 5-year survival rates are around 15-30% for supratentorial lesions and less than 10% for pontine tumors depending on the specific treatment regimen and patient characteristics.
  • The field of neuro-oncology is constantly evolving with a number of clinical trials involving novel agents open for enrollment at any given time.
  • Patients should be evaluated by specialists who are knowledgeable about current treatment approaches and available clinical trials for patients

 

Resources:

  • Ostrom and colleagues have published a comprehensive summary of the epidemiology of central nervous system tumors in the U.S. with data obtained from the CDC, NPCR, and NCI/SEER program (CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011).
  • Finlay and Zacharoulis have published an excellent historical summary of key clinical trials related to the treatment of high-grade gliomas and diffuse intrinsic pontine tumors (Finlay et al. 2005).
  • If you have a patient with a newly diagnosed astrocytoma, they may find the National Cancer Institute’s page on “Childhood Astrocytoma Treatment” helpful: http://www.cancer.gov/types/brain/patient/child-astrocytoma-treament-pdq

 

References:

  1. Linabery MA, Ross JA. Trends in childhood cancer incidence in the U.S. (1992 – 2004). Cancer. 2008; 112(2): 416.
  2. Biegel, JA. Cytogenetics and molecular genetics of childhood brain tumors. Neuro Oncol. 1999; 1(2): 139-151.
  3. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011. Neuro Oncol. 2014; 16(4): iv1-iv63.
  4. Taylor AJ, Little MP, Winter DL, Sugden E, Ellison DW, Stiller CA, Stovall M, Frobisher C, Lancashire ER, Reulen RC, Hawkins MM. Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol. 2010; 28(36): 5287.
  5. Chintagumpala M, Gajjar A. Brain tumors. Pediatr Clin N Am. 2015; 62: 167 – 178.
  6. Claus EB, Black PM. Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001. Cancer. 2006; 106(6): 1358.
  7. Armstrong GT, Conklin HM, Huang S, Srivastava D, Sanford R, Ellison DW, Merchant TE, Hudson MM, Hoehn ME, Robison LL, Gajjar A, Morris EB. Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro Oncol. 2011; 13(2): 223.
  8. Finlay JL, Zacharoulis S. The treatment of high grade gliomas and diffuse intrinsic pontine tumors of childhood and adolescence: a historical - and futuristic - perspective. J Neurooncol. 2005; 75(3): 253-66.

 

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