NORD gratefully acknowledges Thai Tran, NORD Editorial Intern from the Massachusetts College of Pharmacy and Health Sciences and Jeffrey N. Bruce, MD, Professor of Neurological Surgery, Columbia University College of Physicians and Surgeons, for assistance in the preparation of this report
Glioblastomas are aggressive and malignant grade IV brain tumors that originate from the glial cells of the brain. Malignant tumors are tumors that can spread and infect other nearby cells. Glioblastomas originate from a type of glial cell called the astrocyte so they are sometimes called astrocytomas. A grading system from I to IV defines the rate of tumor growth grade I indicating slow growth and grade IV indicating rapid growth. Glioblastomas can often start off as grade IV tumors without any evidence of earlier lower grade tumors.
Glioblastomas can be located anywhere in the brain and do not regularly spread outside of the brain. Common symptoms patients with glioblastoma experience include headaches, seizures, confusion, memory loss, muscle weakness, visual changes, language deficit, and cognitive changes. Glioblastomas tend to affect older individuals (age 45 to 70) with rare occurrences in children. Treatment methods typically include a combination of surgery, chemotherapy, radiation therapy, and alternating electric fields therapy. The average survival time for patients with glioblastoma who have undergone combination treatments of surgery, chemotherapy, and radiotherapy is 14.6 months.
The World Health Organization classifies glioblastomas into 3 main categories. Glioblastoma isocitrate dehydrogenase (IDH)-mutant, glioblastoma IDH-wildtype, and glioblastoma NOS (not otherwise specified). These classifications are based on the presence of an enzyme called IDH. Individuals with glioblastoma IDH-mutant protein in their bodies have a higher overall survival rate than those with glioblastoma IDH-wildtype protein.
Patients with glioblastoma present with two types of symptoms, generalized and focal. Generalized symptoms tend to occur in many types of brain tumors. These symptoms include headaches, seizures, nausea/vomiting, memory loss and decrease in normal function. Focal symptoms are dependent on the location and size of the tumor. The size and location of the tumor often influence the signs and symptoms seen in patients. For example, if the tumor is in the part of the brain required for language processing, the patient may have more issues speaking or understanding speech. Other than having language difficulty, other focal symptoms include seizures, muscle weakness, sensory loss, and visual changes.
Tumors can also cause the brain to swell because of the amount of room they take. Because they grow, they can push on parts of the brain which can lead to headaches, nausea, and vomiting. Glioblastoma is an aggressive, fast-spreading tumor that effects nearby brain tissue.
The exact cause of glioblastoma is unknown. However, there are factors that can influence the risk of glioblastomas. A risk factor known to be associated with glioblastoma is prior ionizing radiation therapy that uses high energy waves/particles to destroy cancer cells but can also cause normal cells to be damaged and even lead to new cancer cells forming. Other risk factors include employment in synthetic rubber manufacturing, petroleum refining, and exposure to vinyl chloride or pesticides. It is important to note that individuals who are diagnosed with glioblastoma may not have any of these risk factors. Likewise, those with these risk factors may never develop glioblastoma in their lifetime. Causation due to risk factors has not been established and further research is needed.
Rare hereditary diseases such as Turcot syndrome, Li-Fraumeni syndrome, and neurofibromatosis are associated with an increased risk of glioblastoma, but they only account for a minority of diagnoses.
3/100,000 people per year are affected by glioblastoma in the United States. The average age of diagnosis is 64 years of age with a slightly higher rate in men than women. Caucasians have the highest rate of glioblastoma diagnoses compared to other ethnic groups such as African-Americans, Asians, and American Indians.
Individuals who are suspected to have a glioblastoma should first undergo a full physical and neurological examination. Neurological examinations are used to assess patient sensory and muscle responses. If any signs or symptoms of glioblastoma are present, the patient will require brain imaging using contrast-enhanced magnetic resonance imaging (MRI). MRI is often used to identify glioblastomas. It is a technique that creates detailed images of the human body. A MRI machine produces a strong magnetic field and directs radio waves towards the body. Computers interpret changes in the body caused by radio waves and produce images. Contrast dye is used to further enhance imaging. This makes it easier to distinguish tumors from normal cells. Although MRI can help identify possible glioblastomas, a tissue sample from a biopsy is required to make any definite diagnosis. A biopsy is an operation that removes tissues. A diagnosis should only be made when these tissues are confirmed to be a form of glioblastoma.
Clinical Testing and Work Up
Many factors can affect disease progression as well as the success of treatment. These are IDH-mutation status, Karnofsky performance status (KPS), and O-6 methylguanine DNA methyltransferase (MGMT) status. As noted before, individuals with IDH-mutated genes have less aggressive tumors with better response to treatment. KPS is an assessment to determine functional capacity. The higher the score, the more activities, and independence the patient can experience. A score of 100 indicates a patient can perform all tasks normally with minor signs of the disease while a score of 50 indicates that the patient requires considerable help in everyday life. Those who score higher in the KPS assessment fair better with treatment. MGMT is an enzyme responsible for DNA repair. These enzymes can influence the effectiveness of chemotherapy-related to glioblastoma. Individuals with the normal form of this enzyme tend to fare better during and after chemotherapy.
Multidisciplinary teams are essential for the treatment of glioblastomas. Each medical professional plays a critical role in treatment. These specialists include but are not limited to neuro-oncologist (diagnose and treat the disease), neurosurgeon (removes tumors), radiation oncologist (provides radiotherapy), nurses (providing necessary support and familiarity for the patient), social workers (help with any social needs), pathologist (distinguish tissue), and neuroradiologist (read MRI images). Treatment options include a combination of surgery, radio therapy, chemotherapy, and alternating electric fields therapy.
Maximal safe surgical resection of the glioblastoma is the first step in treatment. A maximal safe surgical resection means to remove as much as the tumor as possible while minimizing permanent damage to the brain. There are techniques used to increase the amount of tumor removed which include awake craniotomy, fluorescent dye, intraoperative MRI, and endoscopic surgery. Awake craniotomy is performing the surgical removal of the tumor while the patient is awake. For example, if a tumor was located in the part of the brain which is required for speaking, surgery in that area may cause permanent speech deterioration. By having the patient awake and speaking to the surgeon, the patient can guide the surgery and achieve better results. Fluorescent dyes help distinguish the tumor through abnormal blood vessels resulting in more of the tumor being removed. An intraoperative MRI uses radio waves and a magnetic field to create an image of the brain during the operation and is used as a guide for the removal of tumors. An endoscopic surgery, or a minimally invasive surgery, is when a small device is inserted into the brain through a small opening in the head and is used to identify and remove tumors. It is important to note that surgery is not a cure for glioblastoma. Even if there was a 100% removal of the glioblastoma tumor, there are many small undetectable tumor cells still present in the brain.
Radiotherapy, or radiation therapy, is the next step in the treatment. Radiation therapy damages the DNA of tumor cells. This slows or stops the progression of the disease. However, normal cells are also damaged by radiation therapy. Common symptoms from receiving radiation therapy include but are not limited to fatigue, loss of hair, loss of appetite, and skin problems. Due to the severe side effects, radiation therapy is not continued indefinitely.
Chemotherapy can be used during and after radiotherapy as treatment for glioblastoma. Temozolomide is a Food and Drug Administration (FDA) approved therapy for the treatment of glioblastoma. Bevacizumab and Gliadel wafer are chemotherapy agents that have also been approved by the FDA for the treatment of glioblastoma. Bevacizumab helps reduce the number of blood vessels to the tumor site. By reducing the number of blood vessels, the tumor is unable to receive nutrients to grow. Gliadel wafer is the first approved chemotherapy agent to deliver treatment directly to the brain. These wafers are applied to the tumor site. Of these chemotherapy agents, temozolomide is the most effective for the treatment of glioblastoma.
Alternating electric fields can be used with chemotherapy, but not with radiation therapy. This treatment has been approved for both newly diagnosed and recurrent glioblastoma. Individuals must shave their heads and electrodes are attached onto their scalp. These electrodes must stay on for the majority of the time, the longer the patient undergoes treatment, the better the results. The device generates an electric field that alternates back and forth preventing cancer cells from multiplying.
The National Comprehensive Cancer network (NCCN) guidelines encourage patients who are eligible for clinical trials to join them. These clinical trials include but are not limited to therapies directed to those who are unable to receive surgery, immunotherapy, attenuated viral therapies, targeted therapy towards tumor growth factors, and the combination of these therapies.
Currently (2018) there are approximately 300 clinical trials listed with the National Institutes of Health that are investigating glioblastoma. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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