Gliomas

What are gliomas?

Gliomas are cancerous brain tumors that start in glial cells. These are the supporting cells of the brain and the spinal cord. Some types of gliomas grow faster than others.

Glioma is a growth of cells that starts in the brain or spinal cord. The cells in a glioma look similar to healthy brain cells called glial cells. Glial cells surround nerve cells and help them function.

As a glioma grows it forms a mass of cells called a tumor. The tumor can grow to press on brain or spinal cord tissue and cause symptoms. Symptoms depend on which part of the brain or spinal cord is affected.

There are many types of glioma. Some grow slowly and are not considered to be cancers. Others are considered cancerous. Another word for cancerous is malignant. Malignant gliomas grow quickly and can invade healthy brain tissue. Some types of glioma happen mostly in adults. Others happen mostly in kids.

In the United States, there are six cases of gliomas diagnosed per 100,000 people every year. Gliomas are very diffusely infiltrative tumors that affect the surrounding brain tissue.

Are there different types of gliomas?

The most common types of gliomas are:

Astrocytomas: These include a range of tumors, from low-grade astrocytomas to high-grade astrocytomas known as anaplastic astrocytomas and glioblastoma multiforme (GBM), which is the most aggressive and the most common primary brain tumor in adults. Astrocytomas account for around 75.5% of all gliomas.

Ependymomas: Originating from ependymal cells that line the ventricles of the brain and the center of the spinal cord, ependymomas are rarer compared to astrocytomas and oligodendrogliomas. Ependymomas are relatively rare, accounting for approximately 2 to 3 percent of primary brain tumors overall. They represent about 5% of adult intracranial gliomas and can constitute up to 10% of central nervous system (CNS) tumors in children, where they are more common​​​​.

Oligodendrogliomas: These are typically slower-growing tumors that arise from the cells that produce the myelin sheath surrounding nerves. Oligodendrogliomas account for approximately 1.4% of primary brain tumors.

Mixed gliomas: Sometimes, gliomas can have characteristics of more than one of the above types, such as oligoastrocytomas, which have features of both astrocytes and oligodendrocytes. Mixed gliomas are relatively uncommon, constituting about 5% to 10% of gliomas​​​​.

These figures are approximations and the exact percentages can vary depending on the source and the population being studied. It's also worth noting that there are other subtypes and less common forms of gliomas not included in this breakdown.

What are common signs and symptoms of gliomas?

Glioma symptoms depend on the location of the glioma. Symptoms also may depend on the type of glioma, its size and how quickly it's growing.

Common signs and symptoms of gliomas include:

→ Headache, particularly one that hurts the most in the morning.

→ Nausea, vomiting, drowsiness.

→ Confusion or a decline in brain function, such as problems with thinking and understanding information.

→ Memory loss.

→ Personality changes or irritability.

→ Vision problems, such as blurred vision, double vision or loss of peripheral vision.

→ Speech difficulties.

→ Seizures, especially in someone who hasn't had seizures before.

→ Weakness or loss of feeling in limbs

→ Walking difficulties

Headaches are the most common initial presenting symptom of patients with glioma. The pathophysiology of headaches is theorized to be the result of tumor growth that places a mass effect on surrounding tissue. The mass effect, in turn, leads to pressure in the microvasculature and leads to edema. Depending on the location of the tumor in the brain, the mass effect leads to signs of a brain tumor. For example, frontal lobe tumors can present with behavioral changes while dominant temporal lobe tumors can present with receptive speech problems. Other symptoms related to mass effects include nausea, vomiting, and change in vision, Seizures are the second most common symptom of presentation. The pathophysiology of seizures is attributed to tumor irritation to the cerebral cortex that leads to focal or generalized seizures. Other presenting symptoms of gliomas are tingling sensations, weakness, difficulty ambulation, and in rare cases, patients can present in a comatose state due to hemorrhage within the tumor which leads to an acute herniation syndrome.

What causes glioma?

The exact cause of gliomas is not fully understood, but a combination of genetic and environmental factors is believed to contribute to their development. Here are some factors that are associated with an increased risk of developing gliomas:

→ Genetic Predisposition: Certain inherited genetic syndromes, like neurofibromatosis type 1 and 2, Li-Fraumeni syndrome, and Turcot syndrome, can increase the risk of developing gliomas.

→ Ionizing Radiation: Exposure to ionizing radiation, such as radiation therapy used to treat other forms of cancer, has been linked to an increased risk of gliomas.

→ Family History: A family history of gliomas may increase the likelihood of developing these tumors, though familial gliomas are rare.

→ Age: The risk of developing a glioma increases with age, with peak incidence in older adults, although certain types of gliomas, like pilocytic astrocytomas, are more common in children.

→ Chemical Exposure: There is some evidence to suggest that exposure to certain industrial chemicals might be linked to an increased risk of gliomas, although this link is not strongly established.

→ Other Factors: Factors such as race, gender, and a history of allergies or atopic disease have also been investigated for their potential association with glioma risk, with varying levels of evidence.

While these factors can increase the risk, many people with one or more risk factors never develop gliomas, and many who do develop gliomas have no apparent risk factors. This suggests that the development of gliomas is likely due to a complex interplay of multiple factors.

How are gliomas diagnosed and evaluated?

Diagnosing and evaluating gliomas typically involves a combination of clinical assessment, imaging studies, and tissue diagnosis. 

Here's a general overview of the process:

→ Clinical Evaluation: The initial step often involves a detailed medical history and physical examination, with specific attention to neurological function.

→ Neurological Examination: A neurologist may perform a neurological exam to check for vision, hearing, balance, coordination, strength, and reflexes. They may also evaluate mental status and memory to assess functions controlled by the brain.

→ Imaging Studies:

Magnetic Resonance Imaging (MRI): 

MRI is the standard imaging technique for glioma diagnosis. It provides detailed images of the brain and can identify the location, size, and specific characteristics of the tumor.

Computed Tomography (CT):

Sometimes used if MRI is contraindicated or not available.

Advanced MRI Techniques: 

Including functional MRI (fMRI), perfusion MRI, and magnetic resonance spectroscopy (MRS), which can provide more information about the tumor’s activity and composition.

Positron Emission Tomography (PET): 

PET scans can sometimes be used to evaluate the metabolic activity of the tumor.

→ Biopsy:

Surgical Biopsy: 

A neurosurgeon may perform a biopsy where a small piece of the tumor is removed during an operation. The sample is then analyzed by a pathologist.

Stereotactic Biopsy: 

In cases where the tumor is in a difficult-to-reach location, a needle biopsy guided by MRI or CT images may be performed.

Pathological Examination: 

The biopsy sample is examined under a microscope to determine the type and grade of the glioma. Specialized tests such as immunohistochemistry, genetic and molecular testing can provide additional information about tumor biology, which can influence treatment decisions.

Grading: 

Gliomas are graded according to the World Health Organization (WHO) grading system based on the tumor's appearance under the microscope and presence of certain genetic mutations. Grades I and II are considered low-grade gliomas, while grades III and IV are high-grade, more aggressive tumors.

Genetic and Molecular Testing: 

This involves analyzing the tumor for specific genetic mutations, markers, and other molecular features that can provide prognostic information and guide treatment choices, particularly for targeted therapies.

Neuropsychological Assessment: 

For some patients, especially those with tumors that may affect areas of cognition, language, or other specific brain functions, a neuropsychological assessment may be performed.

Once a diagnosis is established, the patient's medical team will evaluate the best treatment options based on the type, size, location, and grade of the glioma, as well as the patient's overall health and preferences. Treatment may include surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of these approaches. Monitoring for changes in the tumor's behavior over time is also an essential part of managing the disease.

What are the different grades of gliomas?

Gliomas are graded according to the following characteristics as seen under a microscope:

Grade I – slow-growing tumors with slowly dividing cells. There is no significant necrosis (cell death) or vascular proliferation (increased blood vessel growth – cancerous tumors create extra blood vessels).

Grade II – slow-growing tumors with more rapidly dividing cells. There is no significant necrosis or vascular proliferation.

Anaplastic grade III – these brain tumors can arise from lower grade gliomas and may develop further into higher grade tumors. They are described as having focal or diffuse areas of high cell division and, therefore, show many dividing nuclei (the small sac within the cell that contains the DNA).

Glioblastoma multiforme (GBM) grade IV – these tumors have similar characteristics to grade III gliomas, but have a higher incidence of vascular proliferation and necrosis.

What are potential treatment options of gliomas?

The treatment of gliomas is complex and depends on several factors, including the type, location, and grade of the tumor, as well as the patient's overall health and preferences. Here is a general outline of the treatment modalities used for gliomas:

→ Surgery: The first line of treatment for many gliomas is surgical resection to remove as much of the tumor as possible while minimizing damage to normal brain tissue. Surgery can alleviate symptoms by reducing pressure in the brain and provides tissue for diagnosis. For some low-grade gliomas, surgery may be the only treatment needed.

The optimal approach for each patient is determined by the tumor location and surrounding normal anatomy. 

These may include:

a) the Endonasal endoscopic route through the nostrils

b) the Supraorbital route through a small eyebrow incision

c) the Retromastoid route through an incision behind the ear

d) gravity-assisted approaches such as the Transfalcine approach

e) to reach tumors located deep in the brain a small tube is guided to the tumor using MRI fiber mapping in order to minimize damage to the healthy surrounding brain. Through the tube the tumor is removed.

While most tumors can be removed using one of the above approaches it is important to note that they are not ideal for all tumors. In some instances such as large tumors near the brain surface a conventional larger craniotomy may be indicated. 

Regardless of the route, the goal is to achieve maximal tumor removal while minimizing manipulation of critical brain structures.

→ Radiation Therapy: This is commonly used after surgery to kill any remaining tumor cells and can be used as the primary treatment when a tumor cannot be surgically removed. Conformal radiation therapy techniques can target the tumor while sparing healthy tissue.

→ Chemotherapy: Chemotherapy drugs can be used to kill tumor cells or stop their growth.

Chemoradiation: Currently, Stupp protocol is a standard of care for Grade III-IV gliomas. The protocol consists of radiotherapy and concomitant chemoradiation using a total of 60 Gray to 2 Gray per daily fraction over 6 weeks and temozolomide. 

→ Tumor Treating Fields (TTF): For certain high-grade gliomas, a treatment known as Tumor Treating Fields involves wearing a device that creates electric fields to disrupt tumor cell division.

→ Targeted Therapy: These treatments target specific abnormalities present within cancer cells.

Targeted therapy for gliomas is a type of cancer treatment that uses drugs or other substances to precisely identify and attack specific cancer cells without harming normal cells. Unlike traditional chemotherapy, which affects all rapidly dividing cells, targeted therapy aims at specific molecular targets that are associated with cancer.

In the context of gliomas, targeted therapies often focus on the molecular and genetic abnormalities that drive the growth and survival of tumor cells. Some examples of targeted therapy include:

Monoclonal Antibodies: These are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. For example, bevacizumab (Avastin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that tumors produce to grow new blood vessels (a process called angiogenesis). By inhibiting angiogenesis, bevacizumab can help starve the tumor of the nutrients it needs to grow.

Tyrosine Kinase Inhibitors (TKIs): These inhibitors target specific enzymes (tyrosine kinases) that are involved in the signaling pathways that control cell growth and division. By blocking these enzymes, TKIs can help to stop the growth of cancer cells.

mTOR Inhibitors: The mammalian target of rapamycin (mTOR) is a protein that regulates cell growth, proliferation, motility, and survival. Inhibitors of mTOR can disrupt these processes in cancer cells.

Signal Transduction Inhibitors: These block the activities of molecules that participate in signal transduction, the process by which a cell responds to signals from its environment. By blocking the signals that tell cancer cells to grow and divide, these drugs can be effective against tumors.

Gene Expression Modulators: These modify the function of proteins that play a role in controlling gene expression.

Apoptosis Inducers: These cause cancer cells to undergo apoptosis, which is essentially programmed cell death.

The identification of specific molecular targets requires detailed knowledge of the tumor's biology, which is often obtained through genetic and molecular testing. However, the effectiveness of targeted therapy can be limited by the presence of the blood-brain barrier, which restricts access to the brain and central nervous system, and by the heterogeneity of the tumor cells, which may have multiple mutations.

Targeted therapies are currently an area of active research in glioma treatment, with numerous clinical trials underway to find new targets and develop new drugs. These treatments can be used alone, but they are often used in combination with other treatments such as surgery, radiation therapy, and chemotherapy.

→ Immunotherapy: This is a newer area of cancer treatment that uses the body's immune system to fight cancer. Various forms of immunotherapy are being studied for gliomas, including checkpoint inhibitors and vaccine therapy.

→ Clinical Trials: Participation in clinical trials can provide access to new and potentially effective therapies that are not yet widely available.

→ Treatments for Recurrence: Options for recurrent gliomas include re-operation with Gliadel wafers and targeted therapy such as angiogenesis inhibitors or immunotherapy. The effectiveness of all these adjuvants therapies is in development.

→ Other Treatments: High-grade glioma patients are prone to seizures, malignant edema, and complication related immobility. Therefore, these patients need antiepileptic medications, deep venous thrombosis (DVT) prophylaxis, and steroids before, during, and after the course of treatments to avoid cerebral edema. 

→ Palliative Care: This is an important aspect of treatment that focuses on relieving symptoms and improving quality of life.

→ Supportive Care: This includes steroids to reduce swelling, antiepileptic drugs to control seizures, and other supportive measures to manage symptoms.

→ Follow-Up and Monitoring: Regular follow-up with MRI scans is necessary to monitor for tumor recurrence or progression.

The approach to treating gliomas is typically multidisciplinary, involving neurosurgeons, neuro-oncologists, radiation oncologists, pathologists, radiologists, and other healthcare professionals. Treatment plans are individualized, and the potential benefits of treatment must be balanced with the risks and possible side effects.

What is the Difference Between Gliomas and Glioblastoma?

Glioma and glioblastoma are both types of brain tumors that arise from the glial cells in the brain. However, there are several differences between these two types of tumors.

Gliomas are a broad category of brain tumors that can be classified into different types based on the specific type of glial cell that they arise from. These include astrocytomas, oligodendrogliomas, and ependymomas. Gliomas are classified by grades I-IV, with grade IV being the most malignant and aggressive.

Glioblastoma, on the other hand, is a specific type of glioma and is classified as a grade IV tumor. Glioblastoma is the most aggressive and malignant form of glioma, and it grows rapidly and spreads quickly to nearby tissues. Glioblastomas are often referred to as glioblastoma multiforme because they contain multiple types of cells.

Another difference between glioma and glioblastoma is their prognosis. While both types of tumors can be difficult to treat, glioblastoma is typically more aggressive and has a worse prognosis than other types of glioma. Glioblastoma also tends to recur more frequently and quickly than other gliomas.