Image 1a. Coronal MRI with contrast of a glioblastoma WHO grade IV in a 15 year old boy

Image 1b. Sagittal MRI with contrast of a glioblastoma WHO grade IV in a 15 year old boy

Glioblastoma (histology slide)

Glioblastoma multiforme (GBM), also known as grade 4 astrocytoma, is the most common and aggressive type of primary brain tumor, accounting for 52 percent of all primary brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBM's occur at only 2-3 cases per 100,000 people in Europe and North America. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Image File history File linksMetadata Download high-resolution version (974x947, 371 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glioblastoma multiforme Metadata This file contains additional information, probably added from the digital camera or scanner used to... Image File history File linksMetadata Download high-resolution version (974x947, 371 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glioblastoma multiforme Metadata This file contains additional information, probably added from the digital camera or scanner used to... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... Image File history File linksMetadata Download high-resolution version (974x954, 343 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glioblastoma multiforme Metadata This file contains additional information, probably added from the digital camera or scanner used to... Image File history File linksMetadata Download high-resolution version (974x954, 343 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glioblastoma multiforme Metadata This file contains additional information, probably added from the digital camera or scanner used to... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... Image File history File linksMetadata Glioblastoma_(1). ... Image File history File linksMetadata Glioblastoma_(1). ... In pathology, Grading is a measure of the progress of tumors. ... Astrocytomas are primary intracranial tumors derived from astrocytes cells of the brain. ... In animals the brain, or encephalon (Greek for in the head), is the control center of the central nervous system, responsible for thought. ... Tumor or tumour literally means swelling, and is sometimes still used with that meaning. ...

Treatment can involve chemotherapy, radiotherapy and surgery; all of which are acknowledged as palliative measures, meaning that they do not provide a cure. The five year survival rate of the disease has remained unchanged over the past 30 years, and stands at less than three percent. Even with complete surgical resection of the tumor, combined with the best available treatment, the survival rate for GBM remains very low. Chemotherapy is the use of chemical substances to treat disease. ... Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... A cardiothoracic surgeon performs a mitral valve replacement at the Fitzsimons Army Medical Center. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ...

Causes

Almost all cases of GBM are sporadic, without a familial predilection, although chromosomal aberrations such as PTEN mutation, MDM2 mutation, and p53 mutation are commonly seen in these tumors. Growth factor aberrant signaling associated with EGFR, and PDGF are also seen. Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... PTEN may mean: PTEN gene - one of the tumor suppressor gene (chromosome 10) Prime Time Entertainment Network ... mdm2 is an E3 ubiquitin ligase that recognizes the N-terminal activation domain (TAD) of the p53 transcription factor. ... TP53 bound to a short DNA fragment. ... The epidermal growth factor receptor (EGFR) is the receptor for epidermal growth factor (EC 2. ... Platelet-derived growth factor (PDGF) is one of the numerous proteins that regulate cell growth and division. ...

Pathogenesis

Glioblastoma multiformes are characterized by the presence of small areas of necrotizing tissue that is surrounded by highly anaplastic cells. This characteristic differentiates the tumor from Grade 3 astrocytomas, which do not have necrotic tissue regions. Although glioblastoma multiforme can be formed from lower grade astrocytomas, post-mortem autopsies have revealed that most glioblastoma multiformes are not caused by previous lesions in the brain. Necrosis (in Greek Νεκρός = Death) is the name given to accidental death of cells and living tissue. ... Look up Tissue on Wiktionary, the free dictionary The word tissue has several meanings: Aerial tissu is an acrobatic art form, and is one of the circus arts. ... Tumor or tumour literally means swelling, and is sometimes still used with that meaning. ... Astrocytomas are intracranial tumors derived from astrocytes. ... Astrocytomas are intracranial tumors derived from astrocytes. ...

Unlike oligodendrogliomas, glioblastoma multiformes can form in either the gray matter or white matter of the brain, but most GBM arises from the deep white matter and quickly infiltrate the brain, often becoming very large before producing symptoms. The tumor may extend to the meningeal or ventricular wall, leading to the high protein content of CSF (> 100 mg/dL), as well as an occasional pleocytosis of 10 to 100 cells, mostly lymphocytes. Malignant cells carried in the CSF may spread to the spinal cord or cause meningeal gliomatosis. However, metastasis of GBM beyond the central nervous system is extremely rare. About 50% of GBM occupy more than one lobe of a hemisphere or are bilateral. Tumors of this type usually arise from the cerebrum, and may exhibit the classic infiltrate across the corpus callosum, producing a butterfly (bilateral) glioma. Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. ... Grey matter (or gray matter) is a major component of the central nervous system, consisting of nerve cell bodies, glial cells (astroglia and oligodendrocytes), capillaries, and short nerve cell extensions/processes (axons and dendrites). ... White matter is one of the two main solid components of the central nervous system. ... In the heart, a ventricle is a chamber which collects blood from an atrium (another heart chamber) and pumps it out of the heart. ... CSF may refer to: California Scholarship Federation California State University, Fullerton, a university in Southern California Cerebrospinal fluid CONMEBOL or CSF (Confederación Sudamericana de Fútbol) City Service Firm, a football hooligan gang attaching themselves to Bristol City football club Classical swine fever Collège de la Sainte Famille... Pleocytosis is a term used to describe a condition of increased white blood cell count in a bodily fluid, such as cerebrospinal fluid (CSF), indicative of an inflammatory, infectious, or malignant condition. ... A scanning electron microscope (SEM) image of a single human lymphocyte. ... In medicine, malignant is a clinical term that means to be severe and become progressively worse, as in malignant hypertension. ... The Spinal cord nested in the vertebral column. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... The Game Boy Micro Game Boy Micro (GBM) is a micro sized Game Boy Advance set for release by Nintendo in the fall of 2005. ... A diagram showing the CNS: 1. ... For other articles about other subjects named brain see brain (disambiguation). ... The corpus callosum is a structure of the mammalian brain in the longitudal fissure that connects the left and right cerebral hemispheres. ... A glioma is a type of primary central nervous system (CNS) tumor that arises from glial cells. ...

The tumor may express a variety of appearance, depending on the amount of hemorrhage or necrosis, or on its age. A CT scan usually shows a nonhomogeneous mass with a hypointense center and a variable ring of enhancement surrounded by edema. Part of a lateral ventricle is usually deformed and both lateral and third ventricles may be displaced. Necrosis (in Greek Νεκρός = Death) is the name given to accidental death of cells and living tissue. ... Edema (American English) or oedema (British English), formerly known as dropsy or hydropsy, is swelling of any organ or tissue due to accumulation of excess lymph fluid, without an increase of the number of cells in the affected tissue. ... The ventricular system is a fluid conducting system within the brain. ...

Symptoms

Although common symptoms of the disease can include seizure, nausea and vomiting, headache, and hemiparesis, the single most prevalent symptom is a progressive memory, personality, or neurological deficit due to temporal and frontal lobe involvement. The kind of symptoms produced depends highly on the location of the tumor, more so than on its pathological properties. The tumor can start producing symptoms quickly, but occasionally is asymptomatic until it reaches an enormous size. See section of Symptoms in: This article is about the medical term, epileptic seizure, as distinct from psychogenic non-epileptic seizure. ... For the Beck song, see Nausea (song). ... Vomiting (also throwing up or emesis) is the forceful expulsion of the contents of ones stomach through the mouth and sometimes the nose. ... A headache is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... Hemiparesis is the partial paralysis of one side of the body. ... The temporal lobes are part of the cerebrum. ... The frontal lobe is an area in the brain of vertebrates. ... In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ...

Main article: brain tumor

A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either found in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), lymphatic tissue, blood vessels), in the cranial nerves (myelin-producing Schwann cells), in the brain envelopes (meninges), skull, pituitary and pineal gland...

Diagnosis

Diagnosis of a suspected GBM on CT or MRI should rest on a stereotactic biopsy or by a craniotomy, which can, at the same time, remove as much tumor as possible. Although the entire tumor can never be removed theoretically due to its multicentricity and diffuse character, partial resection ("debulking") can still prolong survival slightly. A craniotomy is a surgical operation in which part of the skull (part of the cranium) is removed in order to access the brain. ...

Treatment

Treatment of primary brain tumors and brain metastases consists of both symptomatic and palliative therapies.

Symptomatic therapy

Supportive treatment focuses on relieving symptoms and improving the patient’s neurologic function. The primary supportive agents are anticonvulsants and corticosteroids. The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ...

• Anticonvulsants are administered to the ~25% of patients who have a seizure. Prospective studies have failed to show the efficacy for prophylactic anticonvulsants. Those receiving phenytoin concurrent with radiation may have serious skin reactions such as erythema multiforme and Stevens-Johnson syndrome.
• Corticosteroids, usually dexamethasone given 4 to 10 mg every 4 to 6 h, can reduce peritumoral edema (through rearrangement of the blood-brain barrier), diminishing mass effect and lowering intracranial pressure, with a decrease in headache or drowsiness.

Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK, by Parke-Davis, now part of Pfizer) is a commonly used antiepileptic. ... Stevens-Johnson syndrome (SJS) is a severe and potentially life-threatening (15% of cases) disease, it is a hypersensitivity complex affecting the skin and the mucous membranes, a severe expression of erythema multiforme (EM) (and so SJS is also called erythema multiforme major). ... Stevens-Johnson syndrome (SJS) is a severe and life-threatening condition. ... Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. ...

Palliative therapy

Palliative treatment usually is done to achieve a longer survival time, albeit only a slight increase [see below]. It includes surgery, radiation therapy, and chemotherapy.

A maximally feasible resection with maximal tumor-free margins ("debulking") is usually performed along with external beam radiation and chemotherapy. Total cranial irradiation (4500 cGy) with a boosted dose (1500 to 2000 cGy) at the site of the tumor, can increase survival by 5 months [see below]. The addition of the chemotherapeutic agent carmustine alone increases survival slightly. Most oncologists prefer a combination chemotherapy consisting of procarbazine, lomustine, and vincristine (PCV regimen). Another combination includes carboplatin and cisplatin. Their efficacy is limited, and toxicity, particularly with the PCV regimen, can be considerable. Despite initial studies suggesting the superiority of PCV over BiCNU, there are now clear data demonstrating no benefit of PCV over BiCNU in either glioblastoma or anaplastic astrocytoma patients. Brachytherapy (implantation of radioactive beads or needles) and high-dose focus radiotherapy (stereotactic radiosurgery) have not shown to increase survival times. Radiation as used in physics, is energy in the form of waves or particles. ... Chemotherapy is the use of chemical substances to treat disease. ... Irradiation is the process by which an item is exposed to radiation. ... Carmustine is an nitrosourea compound used as an alkylating agent in chemotherapy. ... Procarbazine (Matulane® (US), Natulan (Canada)) is an antineoplastic chemotherapy drug for the treatment of Hodgkins lymphoma and certain brain cancers (such as Glioblastoma multiforme). ... Lomustine (or CCNU) is an alkylating nitrosourea compound used in chemotherapy. ... Vincristine (Oncovin®) is a vinca alkaloid from the Madagascar periwinkle (Catharanthus roseus, formerly Vinca rosea and hence its name). ... Carboplatin is a chemotherapy drug used against some forms of cancer. ... Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e. ... Brachytherapy for prostate cancer is administered using seeds, small radioactive rods implanted directly into the tumour. ...

In a large phase III trial, implantation of BiCNU-impregnated wafers - trade name Gliadel Wafers- at the time of primary resection, improved median survival to 13.9 months, compared with only 11.6 months for placebo wafers (P = .03), in newly diagnosed patients with malignant glioma. Despite initial treatment, virtually all malignant gliomas recur. At relapse, patients may benefit from re-resection, focal radiotherapy techniques (such as radiosurgery), and different chemotherapeutic agents. Depending upon which chemotherapeutic agent was used at initial treatment, temozolomide, procarbazine, or a nitrosourea would be a reasonable conventional choice at recurrence. Clinical trials employing signal transduction inhibitors, epidermal growth factor receptor inhibitors, or antiangiogenic agents may also be available at tumor relapse. Carmustine or BCNU is a mustard gas-related nitrosourea compound used as an alkylating agent in chemotherapy. ... “Placebo effect” redirects here. ... Radiosurgery is a medical procedure which allows non-invasive brain surgery, i. ...

In a recent article, the antimalarial drug chloroquine has been shown to increase mid-term survival when given in combination with conventional therapy (in this case, surgical ablation and carmustine therapy). Further research in this area needs to be done. Chloroquine is a 4-aminoquinoline drug long used in the treatment or prevention of malaria. ...

Another possible therapy technique is to use viruses to attack the cancer. // Surgery; Radiotherapy; Chemotherapy - the conventional triumvirate in our anti-cancer armoury. ...

A recent paper titled "Photodynamic therapy of high grade glioma – long term survival" by Stylli et al. reported on the treatment of glioblastoma multiforme with photodynamic therapy at Melbourne Royal Infirmary, Australia since 1986. Five year survival rates were over 30% with some patients surviving over 10 years. Photodynamic therapy (PDT), developed at Roswell Park Cancer Institute in the 1970s, is a ternary treatment for cancer involving three key components: a photosensitizer, light, and tissue oxygen. ...

Yet another recent - but still experimental - therapy approach is the treatment using nanoparticles. ^[1] These consist of an iron oxide core as well as a cover facilitating the infiltration of the particles into the cancer cells. The particles are injected directly into the tumour. The tumour enriched with the iron oxide particles is then repeatedly warmed via alternating magnetic fields to above 46 degree Celsius. In animal models, considerably improved survival terms arose^[2]; however, at present there aren't any results from sufficiency studies with men yet, but results are expected to be published later this year. It has been suggested that nanopowder be merged into this article or section. ...

Recurrences

Tumor recurrence after surgery or radiation is almost inevitable, usually within 2 cm of the original site, and 10% may develop new lesions at distant sites. Reoperation or brachytherapy has been attempted, with uncertain results. The most aggressive therapy, a second surgery and chemotherapy, is generally used in those under 40 years of age whose original operation was many months earlier. If the PCV regimen has not been used, it may be tried; else, the newer agent temozolomide may be used. However, these regimens usually only increase the symptom-free interval, rather than prolong survival. Brachytherapy for prostate cancer is administered using seeds, small radioactive rods implanted directly into the tumour. ... Temozolomide (brand name Temodar® Schering-Plough Corporation) is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma -- a type of cancerous brain tumor. ...

Prognosis

The median survival time from the time of diagnosis without any treatment is 3 months. Increasing age (> 60 years of age) carries a worse prognostic risk. Death is usually due to cerebral edema or increased intracranial pressure. Cerebral edema is swelling of the brain which can occur as the result of a head injury, cardiac arrest or from the lack of proper altitude acclimatization. ... Intracranial pressure, (ICP), is the pressure exerted by the cranium on the brain tissue, cerebrospinal fluid (CSF), and the brains circulating blood volume. ...

With standard treatment (radiotherapy, chemotherapy (such as temozolomide), and surgery), the median survival is approximately 14 months.^[3] Less than 10% of these patients survive past 5 years. Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Chemotherapy is the use of chemical substances to treat disease. ... Temozolomide (brand name Temodar® Schering-Plough Corporation) is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma -- a type of cancerous brain tumor. ... In probability theory and statistics, a median is a number dividing the higher half of a sample, a population, or a probability distribution from the lower half. ...

It is not well known that there are long term survivors of this disease . Notable among them is Dr. Ben Williams who has been cancer free for over ten years and has treated the disease via a cocktail of drugs.

David M. Bailey is also included among the list of long-term survivors. An inspiration to brain tumor patients and survivors, he has been living cancer-free for more than ten years. His love of songwriting and performing has kept him strong, and has helped him through what some call an "adventure."

References

1. ^ Maier-Hauff et al.: Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme. J Neurooncol. 2007 Jan;81(1):53-60. PMID 16773216
2. ^ Jordan et al.:The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol. 2006 May;78(1):7-14. PMID 16314937
3. ^ Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M, Belanger K, Brandes A, Marosi C, Bogdahn U, Curschmann J, Janzer R, Ludwin S, Gorlia T, Allgeier A, Lacombe D, Cairncross J, Eisenhauer E, Mirimanoff R (2005). "Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.". N Engl J Med 352 (10): 987-96. PMID 15758009. 

Additional reading

Cancer Management: Brain Tumors

External links

• National Cancer Institute Clinical Trials
• North America Brain Tumor Coalition
• German Brain Tumor Association
• Glioblastoma multiforme - A new Viro-therapy developed at the Hebrew University - An IsraCast article
• Emedicine.com article on glioblastoma multiforme
• Young Adults Surviving Glioblastoma support group
• Kayla's Foundation, a foundation based on connecting people affected by GBM and committed to a cure