What Is Glioma & How Is It Analyzed?

Neurons are the key cells in the brain and spinal cord which are responsible for transmitting messages in the brain. While the signals and messages that allow you to think, move, and speak are created by neurons, the glial cells are critical in maintaining brain function.

So essentially, a glioma is a tumor that comes from the brain’s own support cells.

Growth is often not uniform for gliomas. Doctors use a grading system, with four grades, to classify them.

Understanding Glioma Grading

Unlike many other cancers, which are staged based on tumor spread, gliomas are graded based on their appearance under a microscope and their biological behavior. Gliomas are graded on a scale from 1 to 4, with higher grades indicating greater aggressiveness.

Pathologists examine glioma cells for several key characteristics to determine the tumor’s grade.

This analysis includes:

• Cell Appearance: The more abnormal the tumor cells look, the higher the grade.
• Cell Division: A higher number of actively dividing cells suggests faster tumor growth.
• Vessel Formation: The presence of new blood vessels feeding the tumor indicates a more aggressive glioma.
• Necrosis: Dead tumor cells signal highly aggressive tumor behavior.

“Patients with cancer are familiar with two terms. Sometimes the terms grade and stage grade describes how similar the tumor cells are to the normal cells that originated the tumor,” Dr. Castro explains.

“Cells that are different, but not that different under the microscope to those that are normally present in the brain, are called low-grade. And tumor cells that are very different, very aggressive looking under the microscope are called high-grade,” he adds.

How Grade Helps Determine Treatment

Grade 1 gliomas are considered low-grade and the least aggressive. These tumors grow slowly and are most common in children. Pilocytic astrocytomas fall into this category. If complete surgical removal is possible, it can often be curative, meaning no further treatment is needed. Patients who undergo successful surgery have an excellent long-term outlook.

Grade 2 gliomas are still considered low-grade, but they are more complex. These tumors also grow slowly but can evolve into higher-grade gliomas over time. Surgery is the primary approach, but some cases may require radiation, chemotherapy or a new targeted therapy (like vorasidenib).

Grade 3 gliomas are considered more aggressive and high-grade. These tumors grow more rapidly and are considered malignant. A combination of surgery, radiation, and chemotherapy is often required. Treatment aims to slow progression, but recurrence is common.

Grade 4 gliomas, or glioblastomas, are the most aggressive. These fast-growing tumors infiltrate surrounding brain tissue and are the most aggressive form of glioma. Surgery, radiation, and chemotherapy are standard. New experimental treatments and clinical trials may also be options. Glioblastomas require intensive treatment, but research is ongoing to improve survival rates.

A Promising New Treatment

Recently, the Food and Drug Administration (FDA) approved a drug called vorasidenib. “This is an IDH1 and IDH2 inhibitor. It’s a pill that patients can take and can act on the abnormal enzyme that is seen in patients with IDH-mutant glioma and can arrest its activity,” Dr. Castro explains.

IDH (isocitrate dehydrogenase) is an enzyme in our cells that normally helps keep our cells healthy and make energy. When a mutation occurs in the IDH gene that codes for the enzyme, it can lead to cell changes that allow tumor cells to grow and proliferate uncontrollably. This type of mutation occurs in many gliomas. It is not until recently, however, that scientists have found ways to target this mutation to destroy cancer cells.

Targeting The IDH Mutation In Gliomas

For patients diagnosed with a glioma, molecular testing needs to be performed on the tumor to see if an IDH mutation is present.

An IDH inhibitor (such as vorasidenib – brand name Voranigo) is a medication designed to target the mutated IDH enzyme specifically.

“This is important because if we can stop this abnormal enzyme from producing a substance that leads to abnormal cell function, we can stop cell division and proliferation, which leads to the growth of tumors,” Dr. Castro explains.

This drug was found to be most effective in patients with what is called early-stage, low-grade disease, or grade 2 tumors, where the IDH mutation is thought to be very important in tumor growth,” he adds.

The hope is that IDH inhibitor medications can control the tumor for years longer than previously possible.

Questions To Ask Your Doctor

• What grade is my glioma and what are the standard treatment options?
• Have I or can I undergo molecular testing?
• Is targeted therapy with an IDH inhibitor an option for me?
• How will I be monitored during and after treatment?

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