Ependymoma

Reprinted from Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2013. 4
 * Eyob, Bret, Dustin, Faleesa, Jake Osen, Holly Hardin,     Nick ||
 * **Epidemiolgy:** || * Ependymomas of the cerebellum and brainstem are most common in children under 12.
 * Those in the cerebral hemispheres are seen in children or adults and those in the spinal cord are seen in adults. 1 ||
 * **Etiology:** || * Arises predominantly in the cerebellum or brainstem but also in the cerebral hemispheres and spinal cord when oncogenes become activated and tumor suppressor genes become deleted.
 * Loss of chromosome 22 is the most common gene abnormality seen.
 * The etiology of these changes are unknown. 1 ||
 * **Signs & Symptoms:** || The signs and symptoms are: 2
 * Morning headaches
 * Nausea
 * Vomiting
 * Increased intracranial pressure
 * Aducens and pculomotor nerve defects
 * Coordination changes ||
 * **Diagnostic Procedures:** || The most beneficial diagnostic procedures include: 2
 * Magnetic mesonance imaging (MRI)
 * Computed tomography (CT) scan
 * Lumbar puncture ||
 * **Histology:** || Ependymal cells line the ventricles (fluid-filled areas) within the central region of the brain and form part of the pathway through which cerebrospinal fluid (CSF) flows. Tumors starting in these cells are called ependymomas. 3 Ependymomas are well-delineated moderately cellular gliomas. Histological features are perivascular pseudo-rosettes and ependymal rosettes. 4

Four major types according to the World Health Organization (WHO): 4 1. Ependymoma and variants (grade II): 2. Anaplastic (malignant) ependymoma (grade III): An ependymoma with histological evidence of anaplasia. 3. Myxopapillary ependymoma (grade I): Usually occurs in the conus-cauda-filum terminale region, with a generally favorable prognosis. 4. Subependymoma (grade I): Benign tumor with a network of ependymomal cells in a dense glial fibrillary matrix. ||
 * Cellular ependymoma: A variant of ependymoma with visible cellularity, but usually less prominent pseudo-rosette or rosette formation.
 * Papillary ependymoma: A rare variant which looks like choroid plexus papilloma.
 * Clear cell ependymoma: A rare variant which may be confused with oligodendroglioma neurocytoma or metastatic renal cell carcinoma.
 * **Lymph node drainage:** || The central nervous system (CNS) does not contain lymphatic vasculature, so tumors of the CNS do not metastsize through lymphatics. 5 ||
 * **Metastatic spread:** || Grade I ependymomas usually do not metastasize in the adult population. Grades II and III ependymomas typically metastasize along the cerebral spinal fluid (CSF) pathways in the subarachnoid space which seeds other spinal and intracranial regions. Comparatively, childhood ependymomas have a higher rate of metastasizing through the CSF pathways. Subependymomas are considered benign and do not metastasize. 6 ||
 * **Grading:** || The World health organization (WHO) has classified the three different grades of ependymomas. 4
 * Grade I includes Myxopapillary ependymoma which is located in the conus-cauda-filum terminale region and the Subependymoma which is a benign tumor.
 * Grade II include Cellular, Papillary, Clear cell ependymomas.
 * Grade III is a Anaplastic ependymoma which is a ependymoma with histological evidence of anaplasia. ||
 * **Staging:** || The TNM staging system is the most common tool used to stage cancers. With ependymomas, staging of the entire brain and spinal cord becomes very important. 2 If CSF seeding is noted or high risk histology exists then treatment will be altered. When it comes to staging brain and spinal cord cancers, the grade of the cancer becomes very important also. ||
 * **Radiation side effects:** || It is important to avoid critical structures to reduce side effects. Most common initial side effects could be headache or nausea, but late effects from treatment can be more important since many of these patients are children. Loss of motor-sensory effects can result from post surgical treatment, and cortical atrophy and basal ganglia calcifications can occur even with low doses. 3 Chemotherapy and radiation can also cause hearing loss. There can also be a psychological impact from hair loss, and there is always the risk of radiation induced second malignancies. 2 ||
 * **Prognosis:** || The 5-year survival rate for primary CNS tumors during the past 4 decades was 19% (1960-1985) and has risen to overall survival of 35% (1985-2005). 2 Prognostic factors include tumor type, grade, extent, and location. 5 Prognosis is excellent for completely excised tumors. Neurologic function at diagnosis is an important clinical prognostic factor. It is unclear if age plays a role in the prognosis of ependymoma. The Karnofsky preformance scale plans an important role in determining the quantity and quality of neurologic defects. 2

Performance criteria scores: 100: normal, no complaints 90: minor signs of disease, but able to carry on normal activity 80: normal activity comes with effort 70-50: unable to work and level of care required of varying amounts 40: Disabled 10-30: Hospital/institution care required. Disease progressing rapidly 0: Dead ||
 * **Treatments:** || **Surgery** is the Tx of choice. Gross total excision with preservation of neurological function is the goal. 5

**Radiation Therapy** is used for postoperative treatment of ependymomas after subtotal, incomplete, or piecemeal resection. The only exception is with children diagnosed with well-differentiated ependymomas with a very slow growth rate; delaying radiation until later allows the child to grow at a normal rate for several years. In some cases, increased postoperative radiation dose was associated with better tumor control.
 * Primary tumors of the spinal canal can often be treated with a simple posterior field. width 7-8 cm for adult and as small as 5 cm in children with superior and inferior borders encompassing 1-2 vertebral bodies above and below the tumors. Use MRI or CT myelogram to define these borders.
 * Lateral fields can be used to treat the cervical spine area to avoid excessive dose to the hypopharynx and oral cavity; 4-6 megavolts (MV) photons.
 * Wedged pair fields can spare more cerebral cortex.
 * Thoracic and lumbar areas can be treated using a pair of oblique-wedged fields (less dose to anterior organs). Sometimes use both low and high energy together.
 * Lateral fields can be used in females to spare doses to reproductive organs (be aware of kidney location).
 * If large segments of the cord are to be treated, the dose should be calculated at multiple points due to variations in depth and curvature.
 * A craniospinal field is generally NOT standard practice for these tumors even though patients with high-grade tumors have a high rate of neuraxis dissemination.
 * Modern techniques use 3-D conformal irradiation and intensity-modulated radiation therapy ( IMRT) techniques.

Doses: Intramedullary Ependymoma - total dose is 5040 centigray (cGy) / 180 per Fx If more than half of the spinal cord is treated, doses should not exceed 4500 cGy, small segments can tolerate 5500 cGy Ependymoma of the Cauda Equina - total dose 4500-5040 cGy / 180 per Fx In children, limit to 4000-4500 cGy || Brain Lesion: Brain: 45 Gray (Gy): Necrosis, Infarction Brain Stem: 50Gy: Necrosis, Infarction Optic Nerve: 50Gy: Blindness Optic Chiasma: 50Gy: Blindness Retina: 45Gy: Blindness Ear: 55Gy: Chronic serous otitis Craniospinal: Spinal Cord: 20 centimeter (cm) 47Gy: Myelitis necrosis Kidney: 23Gy: Clinical nephritis Esophagus: 55Gy: Clinical stricture, perforation || Reprinted from the International Journal of Radiation Oncology Biology Physics, 2013. 7
 * **TD 5/5:** || Tolerance doses that within 5 years will cause a minimum 5% complication rate. 2
 * **Additional Images** || [[image:Cochlea level.png]]

The above image shows an ependymoma IMRT plan in the axial view at the level of the cochlea.

Reprinted from the International Journal of Radiation Oncology Biology Physics, 2013. 7

The above image shows an ependymoma IMRT plan in the axial view at the level of the temporal lobe. ||
 * **References:** || # Ependymoma. http://radiology.uchc.edu/eAtlas/CNS/235.htm. Accessed June 3, 2013.
 * 1) Washington CM, Leaver D. //Principles and Practice of Radiation Therapy//. 3rd ed. St. Louis, MO: Mosby-Elsevier; 2010.
 * 2) Brain and Spinal Cord Tumors in Adults. American Cancer Society Web site. http://www.cancer.org/acs/groups/cid/documents/webcontent/003088-pdf.pdf. Accessed June 4, 2012.
 * 3) Nervous system: Ependymomas. Atlas of Genetics and Cytogenetics in Oncology and Haematology Web site. []. Accessed June 3, 2012.
 * 4) Chao K, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
 * 5) Fuller C, Adesina A. Ependymoma Pathology Tumor Spread and Staging. Medscape Web site. [|http://emedicine.medscape.com/article/1744030-overview#aw2aab6c11]. Jul 9, 2012. Accessed June 7, 2013.
 * 6) MacDonald SM, Safai S, Trofimov A, et al. Radiotherapy for childhood ependymoma: Initial clinical outcomes and dose comparisons. //Int J Rad Onc Biol Phys.// 2008;71(4):979–986. doi:10.1016/j.ijrobp.2007.11.065. ||

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