Glioblastoma multiforme

 ICD9           = 191|
 ICDO           = 9440/3 |
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 eMedicineSubj  = neuro |
 eMedicineTopic = 147 |
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}} Glioblastoma multiforme, (GBM) also known as grade4 astrocytomais the most common and aggressive type of primary brain tumor, accounting for 52 percent of all primary brain tumors cases.

Treatment can involve chemotherapy, radiotherapyand surgery. The 5 year survival rate of the disease has remained unchanged over the past 30 years, and stands at less than three percent. Even with complete resection of the tumor, combined with the best available treatment, the survival rate for GBM remains very low. Chromosomal aberrations like PTENmutation, MDM2mutation, and p53mutation are commonly seen in these tumors. Growth factor aberrant signaling associated with EGFR, and PDGFare also seen. Tumors of this type may also infiltrate across the corpus callosum, producing a butterfly glioma.

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 multiforme are not caused by previous lesions in the brain. Metastasis of GBM beyond the Central Nervous Systemis extremely rare.

A variant of glioblastoma multiforme is known as gliomatosis cerebri. Instead of a solid tumor, the cancerous cells are more scattered and diffuse. This variant preserves the architecture of the brain, but causes the affected portion of the brain to swell. It is extremely difficult to diagnose.

Symptoms

Although common symptoms of the disease can include seizure, headache, and hemiparesis, the single most prevalent symptom is a progressive memory, personality, or neurological deficit. The kind of symptoms produced highly depends 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. Unlike oligodendrogliomas, glioblastoma multiformes can form in either the gray matter or white matter of the brain. The symptoms can be relieved, on a primary approach, by the administration of chorticotherapy. These drugs act by rearranging the blood-brain barrier and thus reducing brain oedema. Apart from this, not many different drugs have any kind of importance on this situation. Anti-convulsants, analgesics and stomach protection drugs are usually prescribed.

A Computed Tomography(CT) or Magnetic Resonance Imaging(MRI) scan is necessary to characterize the anatomy of this tumor (size, location, heter/homogeneity). However, final diagnosis of this tumor, like most tumors, relies on histopathologicexamination (biopsyexamination) after biopsy or surgery.

Treatment

Treatment of primary brain tumors and brain metastases consists of both supportive and definitive therapies.

Supportive therapy

Supportive treatment focuses on relieving symptoms and improving the patient?s neurologic function. The primary supportive agents are anticonvulsants and corticosteroids.

• Anticonvulsants are administered to the ~25% of patients who have a seizure. Prospective studies have failed to show the efficacy of prophylactic anticonvulsants for patients with brain tumors who have not had a seizure
• Corticosteroids reduce peritumoral edema, diminishing mass effect and lowering intracranial pressure.

Definitive therapy

Definitive treatment of brain tumors includes surgery, radiation therapy, and chemotherapy. The first step is to devise an overall therapeutic plan, which should outline the sequence and elements of multidisciplinary therapy.

Surgery

Surgery, when indicated, is mandatory. The chances of more prolonged survival increase with good surgical approach and removal of tumor with free healthy margins. The neurosurgeon will try to remove as much tumor as possible, regarding the location and the visual appearance of the tumor, which not always is easily distinguishable from normal healthy brain tissue. The extent of tumor excision must be judged upon several factors; age, general condition, involvement of the so called eloquent areas (brain areas with specific and important functions, such as speech or motor skills), are some of the factors the team must deal with. Sometimes, surgery is merely diagnostic. Through medical image, one can diagnose a GBM with great accuracy. In those cases where there is a doubt of any kind, the patient is not a good surgical candidate (eg, elderly) or the family agrees on a more conservative praxis, a biopsy can and should be performed. In most surgical centers, a stereotatic biopsy will be performed, which will take no more than 30 minutes and demands only a small burr hole to be performed. The patient can be discharged the next day or two. With a histopathological diagnosis in hand, the people involved could be certain of the situation and reliant on the decision. After surgery, a number of different choices are available. Radiotherapy and/or chemotherapy are among them.

Radiotherapy

Radiation therapy plays a central role in the treatment of brain tumors in adults. It is the most effective nonsurgical therapy for patients with malignant gliomas and also has an important role in the treatment of patients with low-grade gliomas and metastatic brain tumors. The radiotherapist will prescribe a certain amount of radiation directed at the tumor previous location. The number of discharges will depend on the patients response. In general, any worsening of the clinical condition will prompt the stopping of the treatment. When some improvement is noticed and the patient is young, making it believable that the chances of good survival are real, more radiation will be given. Radiation therapy for high-grade gliomas
An analysis of three studies of high-grade gliomas performed by the Brain Tumor Study Group (BTSG) showed that postoperative radiotherapy doses > 50 Gy were significantly better in improving survival than no postoperative treatment and that 60 Gy resulted in significantly prolonged survival compared with 50 Gy.

Chemotherapy

Malignant gliomas Chemotherapy has a limited benefit in the treatment of patients with malignant gliomas, and there are not many chemical agents capable of detaining this tumor growth. This is one of the less responsive tumors to any kind of medication. In studies using nitrosureas, it does not significantly lengthen median survival in all patients, but a subgroup seems to have prolonged survival with the addition of adjuvant chemotherapy to radiotherapy. Prognostic factors (age, KPS score, and histology) do not predict which patients will benefit from chemotherapy.
Several alkylating agents have antiglioma activity. The nitrosoureas, such as several alkylating agents have antiglioma activity. The nitrosoureas, such as BiCNU or the combination of procarbazine, lomustine , and vincristine (PCV), have been the traditional initial choices for the treatment of patients with malignant glioma. 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.
Temozolomideis a new alkylating agent recently approved by the FDA for the treatment of patients with recurrent anaplastic glioma. It has demonstrated efficacy and is clearly superior to second-line procarbazine in patients with recurrent disease. A randomized phase III trial has not compared temozolomide with a nitrosourea for up-front chemotherapy, but many neuro-oncologists have switched to temozolomide as the initial treatment for all patients with malignant astrocytic neoplasms. This change is not only because temozolomide may have enhanced efficacy over a nitrosourea, but it clearly has less toxicity and is better tolerated. Furthermore, in a multicenter study, concomitant and adjuvant temozolomide produced prolonged survival over radiotherapy alone. Whether just adjuvant temozolomide, which is the standard in the United States, offers the same superior outcome is unknown (the response is not as satisfactory as with other kind of neoplasias, such as certain types of leukemia with other agents).
Alternatively, 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 placebowafers (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.

Viro-therapy

Viro-therapy (Using viruses as treatment against various diseases) is not a new idea and it was recognized As early as the mid 20th Century, when a number of physicians noticed an interesting phenomenon: some of their patients, who suffered from cancer and had an incidental viral infection, or subjected to vaccination, were now improving, experiencing a remission from their symptoms. In the 40's and 50's, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors, and in 1956, one of the first human clinical trials with oncolytic viruses("onco" meaning cancer, "lytic" meaning "killing") was conducted in patients with advanced-stage cervical cancer. Nevertheless, systematic research of this field was delayed for years, due to lack of more advanced technologies.

In 2006 Researchers from the Hebrew Universityhave succeeded in isolating a variant of the Newcastle DiseaseVirus (NDV-HUJ), which usually affects birds, in order to specifically target cancer cells [1]. The Researchers tested the new Viro-therapy on 14 Glioblastoma multiforme patients and achieved promising results for the first time. More advanced clinical trails should be preformed before this treatment can be approval for clinical use.

References

Cancer Management: Brain Tumors

External Links

Glioblastoma multiforme - A new Viro-therapy developed at the Hebrew University- An IsraCast articlede:Glioblastom no:Glioblastoma multiforme pl:Glejak wielopostaciowy

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It uses material from the http://en.wikipedia.org/wiki/Glioblastoma+multiforme Wikipedia article Glioblastoma multiforme.