How Doctors Grade Glioblastoma Brain Tumors

While experts categorize other cancers in stages — based on where they have spread — gliomas are graded based on other criteria. Gliomas rarely spread to other parts of the body, and their grade depends on how the cancer cells behave and grow, says David Peereboom, MD, a neuro-oncologist with Cleveland Clinic in Ohio.

To find out more about a glioblastoma, doctors often recommend surgery to remove as much of the tumor as they can. Once they have tumor tissue, a neuropathologist looks at it under a microscope and performs tests to find details that can point to the best treatment, says Dr. Feldman.

“Under the microscope, a grade 4 glioblastoma typically contains rapidly dividing tumor cells, areas of necrosis, meaning dead tumor tissue, and abnormal blood vessel growth,” says Ranjit S. Bindra, MD, PhD, a Harvey and Kate Cushing professor of therapeutic radiology and professor of pathology with Yale School of Medicine in New Haven, Connecticut.

Other tumors have defined borders, but glioblastoma cells often extend microscopically into the surrounding brain, beyond what’s visible on the scan, says Feldman.

Glioblastoma diagnosis doesn’t just depend on what the tumor looks like under the microscope, says Dr. Bindra. “We now integrate the microscopic findings with molecular testing to determine exactly what type of tumor a patient has,” he explains.

• Isocitrate Dehydrogenase (IDH) Gene Glioblastomas can’t have a mutation in a gene called IDH, which makes glioma grow more slowly.

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• O6-Methylguanine DNA Methyltransferase (MGMT) Promoter Gene The MGMT gene helps cells with self-repair. Tumors that don’t have functioning MGMT may respond better to certain treatments like temozolomide (TMZ), a chemotherapy drug.
• Epidermal Growth Factor Receptor (EGFR) Gene Amplification Extra EGFR boosts cancer cell growth. Because of this, EGFR-positive tumors may not respond as well to treatments like chemotherapy and radiation.
• Telomerase Reverse Transcriptase (TERT) Gene Promoter Mutations TERT mutations prompt faster tumor growth and help cancer cells survive longer. Glioblastomas with TERT mutations may not respond well to some treatments, such as chemotherapy.

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Diagnosis using molecular testing gives your oncology team more information than the grade alone, says Bindra. These tests are performed on the biopsy specimen obtained from the brain.

“The molecular signature of the tumor, particularly MGMT promoter methylation status, helps us discuss the expected benefit of chemotherapy with patients and their families,” says Feldman.

Who Should Get Molecular Testing?

Everyone diagnosed with a glioblastoma should get molecular testing, says Dr. Peereboom, who notes, “it’s always appropriate.”

Bindra recommends comprehensive molecular testing on the tumor tissue as part of your initial diagnostic workup. Molecular testing is now central to finding out what brain tumor you have, says Bindra. “It should not be viewed as an optional add-on performed only after treatment has failed.”

“Tumor grade helps us understand how urgently and aggressively the tumor should be treated,” says Feldman.

Multipronged Approach

Depending on the grade, you may need radiation or radiation plus chemotherapy, says Peereboom.

Targeted Treatment Based on Molecular Testing

Other Factors Guiding Glioblastoma Treatment

While doctors rely on tumor grade to help determine an appropriate care plan, it’s not the only factor. “We do not treat a number in isolation,” says Bindra, who adds that treatment recommendations also depend on:

• Your age and overall health
• Symptoms
• Tumor location
• How much tumor can be safely removed
• Individual preferences and goals

“Treatment decisions should be personalized and made by a multidisciplinary team experienced in caring for patients with brain tumors,” says Feldman.

Clinical Trial Options Based on Grading

Most clinical trials require molecular testing to join. “For instance, a clinical trial eligibility criteria might say something like, ‘This trial is open for patients who have MGMT,’” says Peereboom.

“The pace of research in brain tumors has accelerated substantially, with advances in molecular classification, targeted therapies, immunotherapy, novel drug delivery approaches, radiation techniques, and treatments designed around specific genetic vulnerabilities in the tumor,” says Bindra.

With new information learned through clinical trials, experts are developing more precise treatments, says Bindra. “I am optimistic that these advances will continue to improve outcomes for patients,” he says.

The complex details of a brain tumor diagnosis can feel confusing, but your oncology team can help you understand what’s going on in your body.

Peereboom recommends asking these questions at your next appointment:

• What is my tumor grade?
• Can you explain my pathology report?
• What do my molecular testing results mean for my prognosis and treatment options?
• Which clinical trials am I eligible for?
• Do you have enough tumor tissue to do all the tests you need?

If you don’t understand something your doctor says, you can ask them to explain it more simply. You have every right to fully understand your diagnosis, prognosis, and treatment options.

Your provider may also recommend speaking with a patient navigator or a nurse, who may be able to take more time to explain your diagnosis and your options more fully.