GBM

Glioblastoma maliform (GBM) is the most common and deadliest brain tumor in adults. It accounts for 50% to 60% of all CNS malignancy and 12% to 15% of all intracranial tumors. 1  GBM is more common in men and peaks in the 60s and 70s. 1 In Europe and North America, 2 to 3 per 100,000 people are diagnosed with GBM each year. 1 GBM can develop in the cerebral hemisphere, brainstem, and spinal cord. 1 || Most GBMs occur sporadically. Possible risk factors include: - Alcohol consumption 2 - Ionizing radiation of the brain 3 - Genetic predisposition of 4
 * **Epidemiolgy:** || Amanuel
 * **Etiology:** || <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Amanuel
 * <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Neurofibromitosis
 * <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Tuberous sclerosis
 * <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Von hippel-Lindaue disease
 * <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Li-Fraumeni syndrome
 * <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Turcot syndrome ||
 * **Signs & Symptoms:** || Lindsey

Signs and symptoms for CNS tumors depend on tumor location, associated expansion and surrounding edema. 5 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. 5 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. || Glioblastoma Multiforme (GBM) is characterized by poorly differentiated, often pleoromorphic, neoplastic astrocytes with marked nuclear atypia and high mitotic activity. The presence of vascular (endothelial) proliferation and necrosis are necessary for diagnosis. Variable appearance may have evidence of old and recent hemorrhage, necrosis and areas of firm tissues. 6
 * **Histology:** || Kevin

Histopathology image of Glioblastoma (GBM) 6 || Absence of lymphatics in the brain; therefore no lymphatic drainage due to the blood brain barrier. || Metastasis of glioblastoma beyond the central nervous system is extremely unusual. Malignant cells carried in the cerebrospinal fluid may spread to the spinal cord but is very rare. 7 || The World Health Organization (WHO) grading system has four categories of tumors.
 * **Lymph node drainage:** || Kevin
 * **Metastatic spread:** || Jenn
 * **Grading:** || Jenn

Grade I: tumors are slow growing; non-malignant, and associated with long term survival (pilocytic astrocytoma).

Grade II: tumors are relatively slow growing but sometimes recur as higher-grade tumors. They can be nonmalignant or malignant (low grade astrocytoma).

Grade III: tumors are malignant and often recur as high-grade tumors (anaplastic astrocytoma).

Grade IV: tumors reproduce rapidly and are very aggressive malignant tumors (glioblastoma). 8 ||
 * **Staging:** || Rachel

There is no staging system for brain tumors, although there are staging systems for other CNS malignancies. 9 GBM tumors do not have clearly defined margins. They tend to invade locally and spread along white matter pathways. They are classified as a Grade IV tumor. ||
 * **Radiation side effects:** || Rachel
 * 1) General side effects: hair loss, skin irritation, hearing problems, nausea, vomiting, appetite changes and fatigue. 10
 * 2) Acute reactions: speech problems or muscle weakness, increased intracranial pressure, headache, nausea or double vision. Steroids usually prescribed to minimize these acute effects.
 * 3) 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.
 * 4) 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 overall survival rate for primary Central Nervous System (CNS) tumors during the past four decades has ranged from 19% from 1960 to 1985. However, that number has risen to 35% over the past two decades. Unfortunately, GBMs are still one of the most lethal. This is despite years of research and clinical trials. 11 ||
 * **Treatments:** || Brandon

The main difference between and Anaplastic Astrocytoma and a GBM is that a GBM requires evidence of tumor necrosis for diagnosis. However, the two are treated quite similar. The standard treatment choice is surgery with External Beam Radaition Therapy (EBRT) to follow. The standard dose fractionation is to deliver 50 to 60 Gray (Gy) in 1.8 to 2.0 Gy per fraction. The tumor volume includes 3 centimeters (cm) around the Gross Tumor Volume (GTV) as seen on the preoperative Magnetic Resonance Imaging (MRI) scan. A 1 cm margin to the residual tumor is used for a boost volume. Stereotactic boosts are currently under investigation. 12 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. 11 ||
 * **TD 5/5:** || Ashley

The TD 5/5 is representative of the dose for 5% complication rate in 5 years. 13


 * 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. ||
 * **References:** || Ashley
 * 1) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif; font-size: 10pt; line-height: 1.5;">Glioblastoma Multiform (GBM). National Brain Tumor Society. http://www.braintumor.org/patients-family-friends/about-brain-tumors/tumor-types/glioblastoma-multiforme.html. Accessed June 3, 2013.
 * 2) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Baglietto L, Giles GG, English DR, et al. Alcohol consumption and risk of glioblastoma; evidence from the Melbourne Collaborative Cohort Study. //Int J Cancer//. 2011; 128 (8): 1929–1934.
 * 3) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Cavenee, WK. High-grade gliomas with chromosome 1p loss. //J neurosurg//. 2000; 92 (6): 1080–10811.
 * 4) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Glioblastoma Multiforme. Mount Sinai Hospital. http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/glioblastoma-multiforme. Accessed June 3, 2013
 * 5) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 148-149.
 * 6) Gilobastoma Multiform. Available at: []. Accessed June 5, 2013.
 * 7) Wikipedia. Glioblastoma Multiforme. Available at: [] . Accessed June 6, 2013.
 * 8) The new WHO classification of Tumors affecting the Central Nervous System. Available at: []. Accessed June 6, 2013.
 * 9) Glioblastoma Multiforme. Medscape. Available at: []. Accessed June 7, 2013.
 * 10) Radiation Therapy for Brain Tumors. CancerConnect.com. Available at: []. Accessed June 7, 2013
 * 11) Washington C, Leaver D. //Principles and Practice of Radiation Therapy//. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010.
 * 12) Khan F, Gerbi B. //Treatment Planning in Radiation Oncology//. 3rd ed. Philadelphia, PA. Lippincott Williams & Wilkins; 2012
 * 13) Hall, E. //Radiobiology for the Radiologist//. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012. ||

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