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Glioblastoma

Overview

Closeup of GlioblastomaGlioblastoma Multiforme (GBM) is the most common type of brain cancer. This type of tumor arises from support cells of the brain known as glial cells, or astrocytes. It occurs most frequently in adults 55 and older. This is an aggressive brain tumor, representing the highest grade (Grade IV) of tumors arising from astrocytes in the brain and spinal cord.

Although treatment rarely leads to cure, modern advancements that combine surgery, chemotherapy, and radiation therapy can significantly improve quality of life and length of survival.

Causes and Risk Factors

Cancers arise from normal cells in the body that have undergone certain types of damage to their DNA.  The result of this damage is unregulated growth.  These cells grow in a disordered fashion, pushing against and invading into normal surrounding structures.

While we do not understand all the specifics of how this damage occurs in brain cells, certain risk factors have been identified:

  • Aggressively growing brain tumors are more common in adults over 35 years old.
  • Radiation exposure. Previous exposure to ionizing radiation (XRays, radiation treatments, nuclear waste) is a significant factor for development of glioblastoma.

There is no evidence that electromagnetic radiation from electrical power lines, microwaves, or cell phones are connected to certain types of brain cancer.

These types of radiation are considered to be relatively new and no long-term studies are available yet to confirm or rule out harmful effect on brain tissue.

  • Family history/genetic factors. History of familial brain cancer, or genetic conditions such as NF1, can increase the risk for glioblastoma occurrence.

Symptoms

Symptoms caused by glioblastoma may be from the mass effect of the tumor itself, from swelling (edema) around the tumor, or by tumor cells infiltrating and damaging nearby brain cells.  Symptoms can vary depending on location of the tumor, and include:

  • Headaches, especially in the morning and progressively worsening headaches
  • Persistent back pain
  • Personality changes
  • Altered mental status
  • Nausea and vomiting
  • Vision changes
  • Speech difficulties
  • Muscle weakness/spasms on one or both sides of the body
  • Loss of bladder and/or bowel control
  • Loss of balance and gait instability (ataxia)
  • New onset of seizures or unexplained worsening of existing epilepsy

These symptoms are often vague, and overlap with many other medical conditions.  Evaluation by specialist is required to make a proper diagnosis.

Diagnosis

Because symptoms of Glioblastoma can be vague and nonspecific, a detailed history needs to be taken regarding the nature and duration of symptoms, factors that make symptoms better or worse, and associated factors such as weakness, numbness, or seizures.  This will be followed by a comprehensive neurological exam that looks for deficits, if present, that may be subtle.

The preferred imaging for Glioblastoma is MRI, as this test provides the greatest detail of brain structures. If an MRI cannot be performed, CAT (computer tomography) scan with contrast or PET (position emission tomography) scan can be performed instead.

Glioblastomas have a characteristic appearance on MRI or CAT scan, and the initial decision for surgery can be made based on imaging alone.  In some cases, however, there may be uncertainty, and to develop an exact treatment plan, a firm diagnosis must first be made.  This can be accomplished via stereotaxic biopsy, a surgical procedure that uses computer navigation to place a biopsy needle within the tumor to obtain core samples for analysis.

Tissue collected during biopsy is sent to the laboratory for evaluation under a microscope by the pathologist. Microscopic analysis will show whether tumor is benign (non-cancerous) or malignant (cancerous), what type of cells it derives from, and the grade of tumor.  This information will allow your team to formulate a treatment plan.

Treatment

Treatment of Glioblastoma depends on the location, size, grade of the tumor, your age, overall health, and past medical history.

Initial treatment may include steroid medications to reduce swelling around the tumor, and to decrease pressure on nearby structures.  Anti-seizure medications might also be prescribed.

The preferred initial treatment is maximal safe surgical resection. Computer modeling is used in the operating room to help plan surgical trajectories, and minimize irritation to important structures nearby.  Other tools routinely used to maximize safety include lasers, intraoperative MRI, and even awake surgery.

If part of the Glioblastoma invades an important location of the brain, it may not be possible to safely remove that part of the tumor.  In that case, some tumor material is left behind rather than risk brain damage.  The smaller volume of remaining tumor can then be treated in other ways.

Additional treatment modalities commonly used in combination with surgical resection are radiation therapy and chemotherapy.

Radiation Therapy (RT)

Radiation therapy usually follows resection of the tumor, but sometimes could be used to shrink the tumor before the surgery. Radiation therapy is provided by radiation oncology specialists with the use of a special machine that directs a beam of high-energy particles (X-Rays or protons) to the location of tumor to kill remaining cells and/or shrink the tumor.

Types of radiation therapy include:

Image-guided Radiation Therapy and Intensity-Modulated Radiation Therapy techniques use 3D brain CT images, CT scans or X rays taken before or during the treatment session to deliver beams of radiation of different intensities and angles to the tumor location.

Proton therapy, or proton beam therapy, is used for tumors located near sensitive areas. Protons release most of their energy within the tumor, leaving surrounding tissue relatively undamaged.

The machines that are used for delivering RT have different names, such as GammaKnife, CyberKnife, and LinAc (Linear Accelerator).

Radiation therapy can produce some side effects as well, such as: hair loss, nausea, headaches, tiredness, loss of appetite, red, sore, inflamed skin and other effects, that are more specific to brain tumor location.

Chemotherapy

Chemotherapy is another adjuvant treatment for astrocytomas, commonly used together with radiation therapy to achieve better results. Chemotherapy involves taking a medication, by mouth or IV, that targets tumor cells.

Temozolomide (Temodar) is the most commonly used oral medication for astrocytoma.

Side effects of chemotherapy can include nausea/vomiting/decreased appetite, fever, weakness, hair loss. Severity of effects usually depends on dose and type of drug administered.

Tumor Treating Fields (TTF) Therapy

This type of therapy is used either together with chemotherapy or after radiation therapy, and utilizes the electrical field to disrupt the growth of cancerous cells. During this treatment adhesive pads are applied on the shaved area of your scalp, corresponding to tumor location and the electrical field will be distributed from a wearable device called Optune.

Prognosis, Follow-up, and Rehabilitation

Important factors affecting Glioblastoma prognosis are location of the tumor, overall health of the patient, and functional deficit caused by the tumor or treatments. Your prognosis will be a part of the pre-/post-treatment discussions with your medical team.

During the treatment course you will be under close observation by your medical team. You will have regular check-up appointments, and routine scans will be made to check response to treatment.

Depending on the postoperative course and area of the brain that was involved, you may acquire some deficits, such as vision, balance, motor changes etc. In that case occupational/physical therapy specialists will be involved to speed your recovery and assist in functional restoration.

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