UNMASKING GLIOBLASTOMA: THE MOST AGGRESSIVE BRAIN CANCER

Glioblastoma (GBM) is the most prevalent form of malignant brain tumor in adults. These tumors originate in the brain and are characterized by the rapid growth and multiplication of cancer cells. Glioblastoma can extend into other regions of the brain and spinal cord, and in rare instances, may spread beyond the brain to other areas of the body.

Glioma tumors, including GBM, develop in glial cells, which are essential for supporting nerve cell function. Specifically, glioblastomas form in glial cells known as astrocytes, and are considered the most aggressive type of astrocytoma (a tumor that forms in astrocytes).

Previously referred to as glioblastoma multiforme, this type of cancer is extremely aggressive and can lead to death within six months if left untreated. Early diagnosis and treatment are crucial for extending survival.

Glioblastomas are classified as grade 4 brain tumors according to the World Health Organization (WHO) grading system. While grade 1 and 2 tumors are typically benign and slow-growing, grade 3 and 4 tumors are more advanced.

Glioblastomas:

• Have rapid growth
• Are diffuse, meaning they have tendrils that extend into other parts of the brain
• Are prone to spreading within the brain
• Can recur even after treatment
• Are considered malignant or cancerous

GBMs fall under the category of gliomas, which are brain tumors originating from glial cells. The term “glioblastoma” derives from these cells, while “multiforme” refers to the various forms the tumor can take, adding complexity to its treatment compared to other tumors.

Symptoms of glioblastoma often develop rapidly due to the growing tumor exerting pressure on the brain, which can damage healthy brain tissue. This can lead to:

• Blurred or double vision
• Headaches
• Loss of appetite
• Memory issues
• Mood or personality changes
• Muscle weakness or balance difficulties
• Nausea and vomiting
• Seizures
• Speech difficulties
• Altered sensations, such as numbness or tingling

What Causes Glioblastoma?

Glioblastoma, like other gliomas that form in the brain and spinal cord, is thought to arise from changes in DNA. DNA, found in your genes, provides instructions for cell growth and multiplication. Mutations in DNA can cause cells to multiply uncontrollably, leading to tumor development.

Is Glioblastoma Hereditary?

While it is possible to inherit certain genetic variations that may increase the risk of glioblastoma from your biological parents, inherited cases are rare. Most mutations that lead to glioblastoma occur randomly during a person’s life.

Glioblastoma Grades

Healthcare providers classify brain tumors using a grading system from I (1) to IV (4) based on their behavior. Grade I tumors are the least aggressive, growing slowly, while grade IV tumors, such as glioblastomas, grow rapidly and are more aggressive. By definition, glioblastomas are grade IV tumors. They can be classified as either primary or secondary. Primary GBM develops directly from glial cells, whereas secondary GBM occurs when a grade I glial tumor progresses into a GBM.

Astrocytoma vs. Glioblastoma

Astrocytomas are a form of brain cancer that originates in astrocytes, the cells responsible for providing nutrients to the brain. Both astrocytomas and glioblastomas start in these cells. Previously, glioblastomas were considered grade 4 astrocytomas due to their aggressive nature. However, researchers have identified molecular differences between glioblastomas and astrocytomas, leading to a reclassification. Despite this, both glioblastomas and grade 4 astrocytomas remain highly aggressive brain tumors.

Glioma vs. Glioblastoma

Glioma is a broad category of primary brain cancer that arises from glial cells, which support nerve cells in the brain and spinal cord. Glioblastoma is a specific type of glioma. All grade 4 gliomas, known for their advanced and aggressive behavior, are classified as glioblastomas.

Causes and Risk Factors of Glioblastoma

The exact cause of glioblastoma is unclear, but several factors may increase the likelihood of developing this tumor:

• Prior radiation to the head: Previous radiation therapy for brain tumors or other cancers in the head region can heighten the risk of glioblastoma.
• Exposure to chemicals and carcinogens: Contact with certain chemicals and cancer-causing agents may contribute to genetic mutations leading to glioblastoma.
• Age and gender: Glioblastoma is more common in individuals aged 50 and older, with an average diagnosis age of 64. It is also more prevalent in men.
• Race: The condition is more frequently seen in White individuals compared to Black, Asian, and Indigenous populations.

Types of Glioblastomas

There are two main types of glioblastoma:

• Primary Glioblastoma: This form accounts for about 90% of cases, is highly aggressive, and typically affects older individuals. It is associated with a shorter life expectancy.
• Secondary Glioblastoma: This type generally arises from a lower-grade glioma, typically affects younger people, and is often found in the frontal lobe. The prognosis for secondary glioblastoma is usually better than for primary glioblastoma.

Treatment Plan for Glioblastoma

The primary treatment for glioblastoma begins with surgery to remove as much of the tumor as safely possible. However, due to the microscopic branches glioblastomas form, it’s often not possible to remove the entire tumor surgically. Following surgery, a combination of chemotherapy and radiation therapy is typically administered, with chemotherapy continuing afterward. In cases where elderly patients or those with significant physical limitations are unable to tolerate combined therapy, a modified approach may be considered, focusing on one of the therapies or an adjusted combination.

Glioblastoma Surgery

Surgical success in glioblastoma treatment greatly depends on the expertise of the neurosurgeon. At MD Anderson’s Brain and Spine Center, neurosurgeons utilize cutting-edge technology to maximize the tumor removal while preserving brain function. One such technology is the Brainsuite® intraoperative MRI, which provides real-time imaging during surgery to guide the removal of as much tumor as possible. Additional advanced tools like functional magnetic resonance imaging (fMRI) and navigated transcranial magnetic stimulation (nTMS) are employed to identify and protect critical brain areas involved in speech and motor functions during the operation.

Surgical Options

• Craniotomy: The standard procedure for most brain tumors, including glioblastoma, involves removing a portion of the skull to access the tumor.
• Awake Craniotomy: This specialized procedure is performed when tumors are located in regions controlling essential functions. During the operation, the patient is awakened to help map critical brain areas, enabling the surgeon to avoid these regions while excising the tumor. Despite being awake, patients do not experience pain due to the use of local anesthesia and the brain’s lack of pain receptors. MD Anderson’s neurosurgeons are among the most experienced in the world at performing this complex surgery.
• Laser Interstitial Thermal Therapy (LITT): LITT is particularly useful for tumors that are difficult to reach through traditional surgery. During the procedure, a laser catheter is guided to the tumor using intraoperative MRI. The laser heats the tumor, targeting cancer cells while minimizing damage to surrounding healthy brain tissue.

Radiation Therapy for Glioblastoma

Radiation therapy involves using focused, high-energy beams to target tumor cells that could not be surgically removed. MD Anderson offers some of the most advanced radiation therapy techniques globally, tailoring each treatment plan to maximize effectiveness while sparing healthy brain tissue.

• 3D Conformal Radiation Therapy: This method uses detailed 3D scans to define the tumor’s shape and size, allowing precise targeting with radiation beams that conform to the tumor’s contours, thus protecting nearby healthy tissue.
• Intensity Modulated Radiation Therapy (IMRT): IMRT uses multiple radiation beams of varying intensity to deliver the highest possible dose to the tumor. Special software is used to create a highly-targeted treatment plan that minimizes damage to adjacent healthy tissues.
• Proton Therapy: This specialized form of radiation therapy delivers high energy directly to the tumor while minimizing exposure to surrounding tissue. Though considered experimental for glioblastoma, it may be recommended as part of a clinical trial.
• Stereotactic Radiosurgery (SRS): SRS delivers precise, high-dose radiation to brain tumors without the need for an incision, making it an option for recurrent tumors in patients who have already undergone standard radiation treatments.

Chemotherapy for Glioblastoma

Chemotherapy involves drugs that target and kill rapidly growing cells, including cancer cells. One challenge is delivering these drugs to the brain due to the blood-brain barrier, which protects the brain but also limits the effectiveness of chemotherapy. MD Anderson utilizes the most advanced chemotherapy options available for glioblastoma treatment.

Tumor Treating Fields

This treatment involves wearing a skull cap with electrodes connected to a battery pack for most of the day. The device emits radio waves into the brain to disrupt tumor cell multiplication.

Clinical Trials

Given the difficulty in treating glioblastoma, ongoing research is crucial. MD Anderson is a leader in glioblastoma clinical trials, offering a variety of studies exploring new treatments and combinations of existing therapies. These trials often include personalized approaches tailored to the specific characteristics of each patient’s cancer.

Recurrent Glioblastoma Treatment

Glioblastoma often recurs after initial treatment. When it does, additional surgery or LITT may be options to remove as much of the tumor as possible. Radiation therapy can also be used palliatively to slow tumor growth and alleviate symptoms. However, many standard treatments are less effective against recurrent glioblastoma. Participation in clinical trials, which may offer new or experimental treatments, is often considered for recurrent cases.

Coping with Glioblastoma

Living with glioblastoma presents numerous challenges, affecting both physical and emotional well-being. The symptoms and treatments can significantly impact quality of life, making everyday activities difficult. It can also be challenging for loved ones and caregivers. However, there are resources and support systems available to help manage these challenges.

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