Glioblastoma+Multiforme+(GBM)

Please see Table 15-3 (below) for the histologic classificaton of tumors.¹ || ​Please see Table 15-1 (below) for the WHO Grades and comparisons of grades.³ ||
 * ​Epidemiology: || Incidence of Disease: Is the most common and most malignant of the glial tumors. There is a estimated 17,000 primary brain tumors diagnosed in the United States each year, approximately 60% are gliomas. In adults older than 50 years of age primary glioblastoma multiform accounts for 60% of cases. In younger patients less than 45 years of age secondary glioblastoma multiformes accounts for 40% of cases. Giloblastoma multiforme (GBM) is most common in the United States, Scandinavia, Israel, and Asia. There are about 2-3 new cases per 100,000 people per year. In the United States, glioblastoma multiforme is a little more common in whites. Males have a slightly higher ratio at 3:2. Older people ages 45 - 70 have a higher rate with a mean age of 53. Only about 9% of all cases occurred in children.² ||
 * Etiology: || Risk & Causative Factors: The etiology of GBM is unknown. There are studies that link, cell phone use, head injury, N-nitroso compounds, occupational hazards, and electromagnetic fields. All these studies have been inconclusive.² ||
 * Signs & Symptoms: || Detection and Diagnosis: Headache and lethargy, increased pressure within the brain, vomiting in the morning, seizures, weakness, motor dysfunction, neuroenendocrine abnormalities, and changes in behavior.² ||
 * Diagnostic Procedures: || Diagnosis may be accomplished by use of physical and neurologic examinations, CT, MRI, and biopsy. Physical and neurological examinations are indicated with new onset of any of the symptoms listed above. CT is almost universally available and, with contrast enhancement, is a reliable screening and diagnositc method in many cases. MRI is now more frequently used in patients with malignant brain tumors and may more accurately show the extent of the tumor. The most useful MRI studies are T1-weighted sagittal images, gadolinium-enhanced and unenhanced T1 axial images, and T2-weighted axial images. T1 images better domonstrate anatomy and areas of contrast enhancement; T2 images are more sensitive for detecting edema and tumor.¹ ||
 * Histology: || ​Neuroepithelial.¹
 * Lymph Node Drainage: || ​Absence of lymphatics in the brain; therefore no lymphatic drainage due to the blood brain barrier. ||
 * Metastatic Spread: || ​GBM metastasizes via cerebrospinal fluid but is rare because GBM tends not to invade the subarachnoid space. Rather, they exhibit well-known tendencies to invade locally and spread along compact white matter pathways such as the corpus callosum, internal capsule, optic radiation, anterior commissure, fornix and subependymal regions. Such spread may create the appearance of multiple glioblastomas or multicentric gliomas on imaging studies.² ||
 * Grading: || The current World Health Organization (WHO) classification of primary brain tumors lists GBM as a grade IV astrocyoma.²
 * Staging: || ​Completely staging for most glioblastomas is neither practical nor possible because these tumors do not have clearly defined margins.² ||
 * Radiation Side Effects: || The following side effects are possible with irradiation to the brain. The presence of these side effects varies due to tumor location, tumor size, and treatment technique/total dose.

Fatigue, decrease in blood counts, nausea, vomiting, headaches, skin irritation (on scalp) and short term memory loss can all occur during and shortly after the course of radiation treatment. Hair loss (temporary or permanent) can occur with doses of 20-40 Gy and doses greater than 40 Gy, respectively. Hormone insufficiency (if pituitary gland is in the field) will occur at a dose of 20 Gy. If the retina or lens is in the field, doses greater than 54 Gy can result in vision changes, cataracts or blindness. Serous otitis can occur when the ear falls in the treatment field at doses of 50 Gy. Neurologic deteriorations may be noticeable 6-12 weeks after treatment. Radiation necrosis may become evident 6 months to 3 years post radiation treatment.¹,⁴ ||
 * Prognosis: || Very poor prognosis. Without treatment, survival is approximately 3 months. With treatment, survival increases to approximately 12 months. Fewer than 25% survive up to 2 years and less than 10% survival up to 5 years.² ||
 * Treatments: || "Treatment of anaplastic astrocytoma and glioblastoma is similar. Current recommendations call for surgical resection followed by adjuvant irradiation, with the addition of chemotherapy in selected patients. Because malignant gliomas are infiltrative, even gross total resection inevitably results in tumor recurrence."¹

GBMs are generally treated with surgical resection, followed by 60 Gy of external beam radiation with or without a boost.¹ "Localized irradiation volumes encompass either the contrast-enhanced volume with a 3 cm margin or the peritumoral edema with a 2-3 cm margin. Total standard dose should be 60 to 64 Gy in 1.8 to 2.0 Gy daily fractions. For patients with poor pretreatment prognostic factos and limited expected survival, palliative treatment (30 Gy in 10 fractions in 2 weeks) may provide adequate symptom control without excessively protracted treatment."¹

"An RTOG phase II study of hyperfractionation compared 1.2 Gy twice daily to doses as high as 81.6 Gy and accelerated fractionation using 1.6 Gy twice daily to doses of 48 and 54.4 Gy without significant incrreased survival.

Single-institution results with dose escalation through radiosurgery or brachytherapy boost, in addition to standard external-beam treatment, suggest a survival advantage in glioblastoma patients, although patient selection may account for part of this benefit. Thr RTOG is examining the role of radiosurgery boost plus external-beam irradiaiton in a phase III trial. In patients receiving a radiosurgery or implant boost, reoperation for necrosis is necessary in one third to one half of patiens; approximately the same number require prolonged steroid use.

The combination of intersitial hyperthermia and intersitial brachytherapy is being emplored at several centers, after prliminary results demonstrated the feasibility of this technique."¹

Brain: 45Gy (whole), 50Gy (2/3), 60Gy (1/3) Brainstem (large tumors): 50Gy (whole), 53Gy (2/3), 60Gy (1/3) Ear (acute serous otitis): 30Gy Ear (chronic serous otitis): 55Gy Lens: 10 Gy Optic Chiasm: 50 Gy Optic Nerve: 50 Gy Retina: 45 Gy⁵ || 1. Chao KS, Perez CA, Brady LW. //Radiation Oncology - Management Decisions.// 2nd ed. Philadelphia, PA//:// Lippincott, Williams & Wilkins; 2002:129-156. 2. eMedicine. []. Accessed January 14, 2010. 3. Prados M. //Brain Cancer Atlas of Clinical Oncology.// 1st ed: 280. Hamilton, ON: BC Decker; 2002:280. 4. Washington CM, Leaver D. //Principles and Practice of Radiation Therapy//. 2nd ed. Philadelphia, PA: Mosby, Inc; 2004:736-7. 5. Wikibooks. Radiation Oncology/Toxicity/Emami. []. Accessed January 15, 2010. 6. Digitally Reconstructed Radiographs courtesy of Ginnie Dea, RT(T), Alta Bates Summit Comprehensive Cancer Center.
 * Irradiation Techniques **
 * "Bilateral or medial cerebral hemispheric tumors are best treated with parallel-opposed portals.
 * If the tumor is asymmetric or lateralized, combinations of dual-photos energies (6MV and 20MV) provide better dose distributions, yielding higher tumor doses and diminishing the dose to the uninvolved normal brain.
 * Frontal lesions encompassing only the anterior parts of the lobe can be treated with anterior and lateral isocentric perpendicular beams; the dose distribuion can be optomized with wedges in either or both beams.
 * Midcerebral tumors are best treated with parallel-opposed anterior and posterior portals and lateral portlas, all isocentric and with or without sedges.
 * Posterior parietal or occipaital lesions can be treateed with posterior and lateral isocentric beams, both suitable wedged for dose homogenization.
 * Lesions in the temporal lobe tip are difficult to treat with other than lateral portals unless the patient is flexible enough to touch the chin against the chest so that a sagittal beam does not traverse the lens. In that case, an added lateral portal may result in an acceptable local dose distribution, which could be further improved by a posterior parallel-opposed field."¹ ||
 * TD5/5: || The following organs have the potential of being in the treatment field depending on tumor size and location.
 * Planning Photos: || ​Digital reconstructed radiographs (DRR) of an example of 3D treatment planning conformal irradiation technique in patient with large GBM in frontal region.⁶ ||
 * || [[image:GBMtransverse.png width="447" height="304" align="left" caption="Coronal view of beams"]] ||
 * || [[image:GBM_sagittal.png width="447" height="316" align="left" caption="Sagittal view of beams"]] ||
 * || [[image:GBMfrontal.png width="456" height="308" align="left" caption="Transverse view of beams"]] ||
 * References**

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