GBM

|| The RTOG uses a staging system taking into account; age, Karnofsky performance, histology, mental status, extent of surgery, time between symptoms and treatment onset, neurologic function, and radiation therapy doses. [4] Yet another multifaceted system with room for error. Attatched is a karnofsky performance scale.  || Standard treatment for a GBM is surgery followed by radiotherapy, or a combination of radiotherapy and chemotherapy. The dose typically given is 60 Gy in 1.8-2 Gy fractions. The treatment fields would include the tumor and a 3 cm. margin. When there is a recurrence, repeat resection and brachytherapy may be recommended. Brachytherapy dose would deliver an additional 50-60 Gy, bringing the total dose to 110-120 Gy.[7] || || 2. Prados MD. //Glioblastoma Multiforme: Current Approaches and Tretament Challenges.// Medscape Education Oncology Web site. [|www.medscape.org/viewarticle/714490]. Updated January 19, 2010. Accessed May 28, 2012. 3. //Gilobastoma Multiform//. Available at: []. Accessed May 30, 2012. 4. Washington, Charles M. //Principles and Practice of Radiation Therapy.// Third ed. St. Louis: Mosby; 2010 5. Chao, K.S. Clifford //Radiation Oncology Management Decisions.// Third ed. Philadelphia: LWW; 2011 6. Uddin S, Berman SA, Jarmi T, et al. Neurologic manifestations of Glioblastoma Multiforme. Medscape web site. [|http://emedicine.medscape.com/article/1156220-overview#showall]. April 19, 2010. Accessed May 31, 2012. 7. Kennedy B, Harris J, Bruce JN, et al. Astrocytoma. [|http://emedicine.medscape.com/article/283453-overview#showall]. Jan. 17,2012. Accessed May 31, 2012. 8. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. //Int J Radiat Oncol Biol Phys.// 1991;109-122. []. Accessed May 31, 2012. || Back to Week 2
 * **Epidemiolgy:** || The incidence rate of Glioblastoma multiforme (GBM) is approximately 2.1 per 100,000 per year. [1] The annual number of newly diagnosed cases is estimated around 22,000 in the United States, with 13,000 deaths. There is a slight prevalence in men compared with women, as well as a slight prevalence seen in developed countries and white individuals for unknown reasons. The World Health Organization identifies that the higher-grade tumors account for the majority of primary brain tumors (>75%), and GBM accounts for the majority of malignant tumors. [2] ||
 * **Etiology:** || Ionizing radiation and immunosuppression are risk factors. Astrocytomas occurring in an irradiation portal are sevenfold in those who survived more than three years after treatment for childhood malignancies with high radiotherapy doses. Syndromes such as Cowden’s syndrome, Li-Fraumeni, Turcots and Neurofibromatosis type 1 are autosomal dominant and can be associated with astrocytomas. Li-Fraumeni is associated with a p53 germ line mutation. Approximately 12% of families with this germline mutation have brain tumors. Turcot’s syndrome consists of a group of autosomal dominant disorders characterized by glioblastomas. They result from an alteration in the genes MLH1 and PSM2. These are found on chromosomes 3 and 7, respectively. Other risk factors implicated but not yet proven include the ingestion of nitrosamines, work in the petroleum industry, exposure to electromagnetic radiation, and ingestion of aspartame. [1] ||
 * **Signs & Symptoms:** || General symptoms can include seizures, headaches, weakness or numbness, depression, nausea due to the increase of pressure within the skull. [1] Depending on specific tumor location symptoms may include limb numbness, memory loss, vision changes, and mood or personality changes. Hemiparesis is the most common symptom resulting in weakness in one side of the body or total paralysis of a limb. ||
 * **Diagnostic Procedures:** || MRI is the preferred diagnostic method for identifying location and volume. MRI will be combined with several other methods to have a final stage, these include. * CT with or without contrast
 * PETCT
 * Biopsy or craniotomy (definitive diagnosis)
 * Stereotactic biopsy ||
 * **Histology:** || This glioblastoma multiforme (GBM) demonstrates marked cellularity with marked hyperchromatism and pleomorphism[3]. Note the prominent vascularity as well as the area of necrosis at the left with neoplastic cells palisading around it[3]. The cells of a GBM can infiltrate widely, particularly along white matter tracts, and even through the CSF[3].
 * **Lymph node drainage:** || Since there is an absence of lymphatics in the brain, there is no lymphatic drainage due to the blood brain barrier. ||
 * **Metastatic spread:** || A metastasis from a lung carcinoma occurs in GMB[3]. Metastases most often appear at the border of the grey and white matter in the distribution of the middle cerebral artery, as in this case, because that is where the blood flow (vascular distribution) is most likely to take metastases[3]. ||
 * **Grading:** || The grade of a tumor is based on its aggressiveness of growth and cellular differentiation. Grade is determined by microscopic examination of tumor cells and is important in predicting the prognosis of a CNS tumor diagnosis. Grade and stage give the physician an accurate description of the tumor so that they may treat it effectively. CNS tumors can be grouped in to benign, low-grade or malignant, and high grade. A system known as the Kernohan Grading System, which is a four grade system has also been used. This system takes in to consideration; cellularity, anaplasia, mitotic figures, giant cells, necrosis, blood vessels and proliferation. Because of the many factors, this grading system is confusing and difficult to use. [4] ||
 * **Staging:** || There are no universal staging systems for CNS tumors, which can be confusing and can lead to problems when diagnosing. The American Joint Committee on Cancer uses a GTM system; grade (G), Tumor type (T), and Metastasis (M).
 * **Radiation side effects:** || Depending on the location, treatment type, and extent of expansion around the tumor site, many side effects are possible but not all likely. Many of them include:
 * Nausea vomiting
 * Radiation dermatitis
 * Hair loss in treatment field
 * Inflammation of outer middle or inner ear and other ear damage, if in the treatment area, may cause temporary or permanent hearing loss.
 * Fatigue
 * Blood counts may decrease with large treatment volumes
 * Somnolence syndrome, occurs 6-12 weeks post radiation caused by damage to oligodendroglial cells.
 * Focal radiation necrosis can appear 6 months to years post radiation.
 * <span style="color: #7030a0; font-family: 'Times New Roman','serif'; font-size: 16px;">Cataracts, retinopothy if eye is included in field
 * <span style="color: #7030a0; font-family: 'Times New Roman','serif'; font-size: 16px;">Visual degradation if the optic nerve and or chiasm are included with blindness at doses of 50 to 55 Gy.
 * <span style="color: #7030a0; font-family: 'Times New Roman','serif'; font-size: 16px;">Hypothalamic-pituitary doses of 20 Gy or more can cause insuficiant hormone production. Brain irradiation can impact critical thinking, short term memory, and learning ability.[5] ||
 * **Prognosis:** || Glioblastoma Multiforme (GBM) is a grade IV tumor. It is aggressive and spreads quickly to nearby tissue. Sometimes GBM's have progressed from a Low-Grade Astrocytoma or an Oligodendroglioma.[6] The average survival is less than 1 year.[7] ||
 * **Treatments:** || [[image:uwlmedicaldosimetry2012/GBM_HMPAO_MR_ar.jpg width="224" height="282" caption="MRI and MRI-SPECT fusion of a GBM"]]
 * **TD 5/5:** || ** TD 5/5 values from Emami 1991 [8] **
 * **References:** || 1. Lenhard RE, Osteen R, Gansler T. //The American Cancer Society’s Clinical Oncology//. Williston, VT: Blackwell Publishing, Inc; 2001.