Glioblastoma multiforme (GBN) is a quickly growing glioma, which develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of nerve cells inside the brain. This is often called grade IV astrocytoma. As the most invasive type of glial tumors, they rapidly grow and commonly spread into nearby brain tissue.
Glioblastoma multiformes can occur “de novo'' or evolve from lower-grade astrocytomas or oligodendrogliomas. For adults, Glioblastoma multiforme occurs most often in the cerebral hemispheres, especially in the frontal and temporal brain lobes. Glioblastoma multiforme is a devastating brain cancer, typically resulting in death within the first 15 months after diagnosis.
Glioblastoma multiformes present unusual treatment challenges due to the following characteristics:
- Localization of tumors in the brain
- The variably disrupted tumor blood supply which inhibits effective drug delivery
- Inherent resistance to conventional therapy
- Tumor capillary leakage, resulting in an accumulation of fluid around the tumor; (peritumoral edema) and intracranial hypertension
- Limited capacity of the brain to repair itself
- Migration of malignant cells into adjacent brain tissue
- A limited therapy response
- The resultant neurotoxicity of treatments directed at gliomas
PREVALENCE AND INCIDENCE
The National Cancer Institute estimates 22,850 adults (12,630 men and 10,280 women) were diagnosed with brain and other nervous system cancer in 2015. In 2015, 15,320 diagnoses led to death.
This condition has an incidence of 2-3 per 100,000 adults per year, and accounts for 52%of all primary brain tumors. Overall, Glioblastoma multiforme accounts for about 17% of brain tumors, both primary and metastatic. These tumors tend to occur in adults between the ages of 45-70. Between 2005-2009, the median age for death from cancer of the brain and other areas of the central nervous system was age 64.
Symptoms vary depending on the location of the brain tumor, but can include any of the following:
- Persistent headaches
- Double or blurred vision
- Loss of appetite
- Changes in mood and personality
- Changes in ability to think and learn
- New onset of seizures
- Speech difficulty of gradual onset
Sophisticated imaging techniques can precisely determine the location of brain tumors. Diagnostic tools include CT or CAT scans and MRIs.
Intraoperative MRI can help during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy (MRS) examines the tumor's chemical profile, with positron emission tomography (PET scan) detecting tumor recurrence.
After a brain tumor is detected on a CT or MRI scan, a neurosurgeon obtains tumor tissue for a biopsy. The tissue is then examined by a neuropathologist.
The analysis of tumor tissue under a microscope is used to assign the tumor a name, grade, and provide these answers:
- From what type of brain cell did the tumor arise?
- Are signs of rapid growth present in the tumor cells?
- Are there any specific genetic mutations within the tumor that can help with prognosis and/or provide a target for therapy?
The tumor name and grade assist in determining treatment options, providing important information for prognosis.
The mainstay Glioblastoma multiformes treatment is surgery, which is followed up by radiation and chemotherapy. The primary objective of surgery is to remove the largest portion of the tumor as possible without injuring surrounding normal brain tissue, which is required for normal neurological function (motor skills, speaking, walking, etc.). Nevertheless, Glioblastoma multiformes are surrounded by a zone of migrating and infiltrating tumor cells. These invade surrounding tissues, removing the possibility of extracting the whole tumor. Surgery creates the ability to reduce solid tumor tissue located in the brain, remove the cells in the center of the tumor that can be resistant to radiation as well as chemotherapy, and reduce intracranial pressure. Surgery, through debulking the tumor, can prolong the lives of some patients and/or improve the quality of their remaining life.
Surgeons can perform a craniotomy and open the skull to reach the tumor site. With computer-assisted image-guidance, this can be completed, sometimes utilizing intraoperative mapping techniques to determine the locations of the motor, sensory, and speech/language cortex. Intraoperative mapping typically involves operating on a patient while they remain awake. The surgeon maps out the anatomy of their language function during the operation. The doctor then decides which portions of the tumor are safe to resect.
Post-surgery, when a wound is healed, radiation therapy can begin. The goal of radiation therapy is to selectively kill remaining tumor cells, which have infiltrated surrounding normal brain tissue. In standard external beam radiation therapy, multiple sessions of standard-dose "fractions" of radiation are delivered to the tumor site as well as a margin in order to treat the zone of infiltrating tumor cells. Each treatment induces damage to both healthy and normal tissue.
By the time the next treatment is given, most of the normal cells have repaired the damage, but the tumor tissue has not. This process continues to be repeated for a total of 10-30 treatments, usually given once a day for five days a week, depending on the type of tumor. The use of radiation therapy supplies most patients with improved outcomes and longer survival rates, as compared to surgery alone or the best supportive care.
Radiosurgery is a treatment method, which uses specialized radiation delivery systems. These direct radiation at the site of the tumor and minimize the radiation dose provided to the surrounding brain. Radiosurgery can be used in select cases for tumor recurrence, typically utilizing additional information derived from MRS or PET scans. It is rarely used in the initial treatment of Glioblastoma multiforme.
Patients undergoing chemotherapy are administered special drugs, which are designed to kill tumor cells. Chemotherapy with temozolomide is the current standard of Glioblastoma multiforme treatment. The drug is generally administered each day throughout radiation therapy. Later, it is provided for six to 12 cycles post-radiation. Each cycle lasts for 28 days (temozolomide given the first five days of each cycle) and is followed by 23 rest days. Even though the aim of chemotherapy is long-term tumor control, it only works for about 20% of patients. The decision to prescribe other forms of chemotherapy to treat tumor recurrence is based on a patient's overall health and type of tumor, along with the extent of the cancer. Before considering chemotherapy, patients should talk about this decision with their oncologists and/or neuro-oncologists.
Because surgery, radiation and chemotherapy are unlikely to provide prolonged remission of Glioblastoma multiforme tumors, researchers continue to investigate new treatments for when the first line therapy has failed. These treatments are completed in clinical trials. Some are available on an investigational basis at centers specializing in brain-tumor therapies (gene therapy, highly focused radiation therapy, immunotherapy, and chemotherapies utilized in conjunction with vaccines). While some of these display promise, the most effective therapies introduced over the past 30 years have improved median survival of Glioblastoma multiforme patients by an average of only three months.