Anaplastic+Astrocytoma

Anaplastic Astrocytomas are rapidly growing tumors that are more aggressive than Grade II astrocytomas. 1  Approximately 65% of anaplastic astrocytoma arise in the cerebral hemispheres, 20% in the thalamus and hypothalamus, 15 % in the region of cerebrum and brain stem. 1 Anaplastic Astrocytomas are rare and accounts for 2% of all brain tumors. 1  Anaplastic astrocytomas have a non-uniform appearance and often invade neighboring tissue. 1  This form of cancer more commonly occur in adults between age 30 and 50. || The cause of Anaplastic Astrocytoma is commonly sporadic. However, a small portion is suspected to be caused by hereditary predisposition including neurofibromatosis type I, Li-Fraumeni syndrome, hereditary nonpolyposis colorectal cancer, and tuberous sclerosis. 1 Anaplastic Astrocytoma can also occur from vinyl chloride and high dose radiation to the brain. 1 ||
 * **Epidemiolgy:** || Amanuel
 * **Etiology:** || Amanuel
 * **Signs & Symptoms:** || Lindsey

Signs and symptoms for CNS tumors depend on tumor location, associated expansion and surrounding edema. 2 Tumor growth along with edema may cause focal neurologic dysfunction, increased intracranial pressure and/or hydrocephalus. With significant cerebral edema or hydrocephalus, nausea and vomiting, headache, and papilledema (swelling of the optic nerve caused by increased intracranial pressure) are common. Headaches may be worse in the morning and focal neurologic deficits are also common. Long term increased intracranial pressure may lead to optic atrophy and even blindness. Seizures are also common, usually with low grade neoplasms. Lumbar back pain, bowel or bladder dysfunction may suggest lumbar metastasis. ||
 * **Diagnostic Procedures:** || Lindsey

Initial workup for CNS tumors includes a complete history and physical. 2 Following history and physical, a complete neurological exam should be performed including assessment of mental condition, cranial nerves, coordination/cerebellar function, sensation, power and reflexes. Ophthalmoscopy checks for papilledema as a sign of increased intracranial pressure should also be done. For MRI, T1 weighted images with and without gadolinium contrast, T2 weighted images, and fluid attenuated inversion recovery (FLAIR) images are all most useful. T1 weighted images show anatomy more clearly as well as areas of contrast enhancement. T2 and FLAIR images are more sensitive for detecting edema and tumor hyperintensity. CT with contrast is also useful. Staging of the neuraxis is essential for neoplasms at high risk of spread to cerebrospinal fluid (CSF). Neuraxis imaging is usually achieved with gadolinium enhanced MRI of the spine. Spinal imaging is usually combined with CSF cytology for complete neuraxis staging. Biopsy is also recommended for CNS tumors. However, selected patients with imaging and symptoms consistent with low grade glioma may be followed closely without biopsy. || Histology of Anaplastic Astrocytoma:
 * **Histology:** || Kevin
 * Poorly differentiated or high-grade tumors.
 * Highly cellular neoplasms that are mitotically active and have potential for metastasis.
 * Very Aggressive tumor. 3

Microscopic histologic anaplastic astrocytoma. 3 || Absence of lymphatics in the brain; therefore no lymphatic drainage due to the blood brain barrier. || It’s an aggressive tumor that frequently infiltrates adjacent normal brain tissue and often spreads outside of the central nervous system. || Grade is determined by microscopic examination. CNS tumors can be grouped into benign, low-grade or malignant, and high grade. The Kernohan is a grading system that defines progressive malignancy of astrocytomas.
 * **Lymph node drainage:** || Kevin
 * **Metastatic spread:** || Jenn
 * **Grading:** || Jenn

Grade I: tumors are benign astrocytomas. Grade II: tumors are low-grade astrocytomas Grade III: tumors are anaplastic astrocytomas. Grade IV: tumors are glioblastomas. 4 ||
 * **Staging:** || Rachel

There is no recognized staging system for astrocytomas. 5 Instead the grading system is used. Anaplastic Astrocytomas are considered a high grade astrocytoma and are classified as a Grade III tumor. ||
 * **Radiation side effects:** || Rachel
 * General side effects: hair loss, skin irritation, hearing problems, nausea, vomiting, appetite changes and fatigue. 6


 * Acute reactions: speech problems or muscle weakness, increased intracranial pressure, headache, nausea or double vision. Steroids usually prescribed to minimize these acute effects.


 * Delayed reactions: These usually occur between one and three months after treatment. These include loss of appetite, sleepiness, lack of energy and an increase in pre-existing neurological symptoms. These reactions are thought to be due to temporary disruption to the nerve coverings. These symptoms are usually temporary, lasting about six weeks or the time it takes for the myelin to repair itself. Swelling is also another effect as a result of the build up of dead tumor cells.


 * Long term effects: These effects are permanent and include decreased intellect, memory impairment, confusion, personality changes, and alteration of the normal function of the area irradiated. ||
 * **Prognosis:** || Brandon

The prognosis is overall poor for Anaplastic Astrocytomas. The overall survival rate is better with a high Karnofsky Performance Score (KPS) and good margins after surgery. However, even with the addition of External Beam Radiation Therapy (EBRT), the 5 year survival rates vary from 20% to 35% in many studies. 7 ||
 * **Treatments:** || Brandon

The primary treatment choice for Anaplastic Astrocytoma is surgery. This is followed by adjuvant EBRT, and in some cases may also be accompanied with chemotherapy. To determine the irradiation volume, a Magnetic Resonance Imaging (MRI) scan is performed and then fused with a planning Computed Tomography (CT) data set. Once these two are fused, the physician as able to see the extent of disease and draw his/her volumes for treatment.

These volumes should include the contrast-enhanced volume with a 3 centimeter (cm) margin **__or__** the peritumoral edema with a 2 to 3 cm margin. The doses that are usually used for these treatments are 60 to 64 Gray (Gy) in 1.8 to 2.0 Gy per fraction. However, if the patient has a poor prognosis and disease is pronounced throughout the brain, whole brain irradiation may be done. This technique goes to a total dose of 30 Gy in 10 fractions. There is also evidence that brachytherapy and hyperthermia may play a role in treatment as well. 8 It should be noted that depending on tumor site, the Organs at Risk (OR) may include the lens of the eye, optic nerve, optic chiasm, brainstem, parotid galnd(s), and spinal cord. 7 ||
 * **TD 5/5:** || Ashley

The TD 5/5 is representative of the dose for 5% complication rate in 5 years. 9


 * Lens: 1000cGy (Cataract)
 * Retina: 4500cGy (Blindness)
 * Optic Nerve: 5000cGy (Blindness)
 * Optic Chiasm: 5000cGy (Blindness)
 * Cochlea: 5500cGy
 * Pituitary: 4500cGy (Hypopituitarism)
 * Brainstem: 5000cGy (Infarction, Necrosis)
 * Spinal Cord: 4700cGy (Infarction, Necrosis)
 * Brain: 4500cGy (Infarction, Necrosis)

*Note: The information above is indicative of total organ limitations. || > []. Accessed June 6, 2013.
 * **References:** || Ashley
 * 1) Anaplastic carcinoma. Boston Children’s hospital. []. Accessed June 3, 2013
 * 2) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 148-149.
 * 3) Kennedy B. //Astrocytoma//. Emedicine. 2012. Available at: [|http://emedicine.medscape.com/article/283453-workup#a0723]. Accessed: June 5, 2013.
 * 4) Wikipedia. Grading of Tumors of the central nervous system. Available at:
 * 1) Childhood Astrocytomas Treatment. National Cancer Institute. Available at: [] Accessed June7, 2013.
 * 2) Radiation Therapy for Brain Tumors. CancerConnect.com. Available at: []. Accessed June 7, 2013.
 * 3) Washington C, Leaver D. //Principles and Practice of Radiation Therapy//. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 897.
 * 4) Chao K, Perez C, Brady L. //Radiation Oncology Management Decisions//. 2 nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.
 * 5) Hall, E. //Radiobiology for the Radiologist//. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012. ||

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