Technology, clinical trials offer hope after glioma diagnosis

By Jessica Saenz

Gliomas are a type of tumor that develops from the glial cells, which surround nerve cells in the brain and spinal cord and help them function. Though some gliomas are slow-growing, many are fast-growing and aggressive.

Gliomas can cause side effects like headaches, nausea and vomiting, vision problems, speech difficulties, weakness and seizures that can make it difficult for people to live a normal life. The size and location of a tumor can also affect treatment, quality of life and prognosis.

While a glioma diagnosis is always serious, Terry Burns, M.D., Ph.D., and Alfredo Quiñones-Hinojosa, M.D., Mayo Clinic neurosurgeons, say advancements in technology and clinical trials offer hope.

Technology is improving existing treatments.

Surgery

Glioma treatment is more effective when most of the tumor is surgically removed, but Dr. Burns says removing tumor tissue from certain parts of the brain can be dangerous. "Some tumors infiltrate important brain areas involved in cognitive function, language and movement," he says.

Dr. Quiñones-Hinojosa adds, "The closer the tumors are to the brain stem, the higher the risk of deficits like weakness of the extremities, difficulty with balance, nerve function and deficits in movements of the face, eyes and mouth."

Improved technology is helping neurosurgeons remove more tumor tissue and minimize harm. These technologies include computer-assisted brain surgery, which uses imaging to guide a surgeon to the areas that require treatment, and brain-mapping techniques, which identify the areas of the brain that control vision, speech and movement to perform surgery without reducing brain function. "We have fluorescent dye that helps us see the tumor cells, intraoperative MRI and more advanced mapping techniques to make surgery safer. Collectively, these technologies now enable us to safely offer surgery for certain tumors that were historically considered too dangerous to remove," says Dr. Burns.

"We have fluorescent dye that helps us see the tumor cells, intraoperative MRI and more advanced mapping techniques to make surgery safer. Collectively, these technologies now enable us to safely offer surgery for certain tumors that were historically considered too dangerous to remove."

Dr. Terry burns

Radiation therapy

Radiation therapy is commonly used to treat gliomas, and new approaches can focus more radiation on the tumor with fewer side effects. "Radiating large volumes of the brain impairs memory and causes fatigue. Proton therapy allows us to radiate certain gliomas while reducing risk to other parts of the brain," says Dr. Burns. Compared to X-ray radiation therapy, proton therapy is more precise, using positively charged particles in an atom (protons) that release their energy within the tumor. Because proton beams can be more finely controlled, healthcare professionals can safely deliver higher doses of radiation to tumors.

"Radiating large volumes of the brain impairs memory and causes fatigue. Proton therapy allows us to radiate certain gliomas while reducing risk to other parts of the brain."

Dr. Terry burns

Radiation therapy can cause side effects, which can be more severe in some people. Dr. Burns says learning who radiation affects more severely and why could help healthcare professionals reduce the side effects of radiation toxicity in people who are more sensitive to it. "Some patients are more impacted by radiation than others, and researchers are working to understand if there are genetic predispositions that might help us identify those patients ahead of time," he says.

Mayo Clinic researchers have pioneered strategies to reduce the side effects of radiation therapy, including hippocampal-sparing radiation and the use of memantine. The hippocampus is the part of the brain that sends memories to be stored and then recalls them later. Hippocampal-sparing radiation reduces the radiation dose to the hippocampus, lessening memory impairment. Memantine is a drug given to people receiving radiation therapy to the brain to help prevent cognitive decline. "We also have clinical trials where we're using a special imaging modality called F-DOPA PET that helps light up the tumor so even if areas of tumor did not show up on a regular MRI, radiation can be focused to those areas we see by PET while avoiding areas that don't need it," says Dr. Burns.

Tumor treating fields

A newer treatment called tumor treating fields (TTF) therapy uses an electrical field to disrupt cancer cells' ability to multiply. "People have to shave their heads and wear sticky pads attached to their heads. It does mean carrying a battery pack; not everyone loves the hassle factor and some folks can experience local skin irritation. Otherwise, TTF has virtually no other side effects and is an additional tool in our arsenal," says Dr. Burns.

Clinical trials are helping to expand glioma treatment options.

Slowing disease progression

Dr. Burns is hopeful about the results of a recent clinical trial that showed that isocitrate dehydrogenase (IDH) inhibitors, targeted therapies historically used to treat IDH-mutated acute myeloid leukemia, can slow the progression of low-grade gliomas with an IDH mutation."Low-grade gliomas inevitably evolve into high-grade gliomas. If we can keep the tumors at bay longer with an IDH inhibitor, it may allow us to prolong the time before we need to use chemotherapy and radiation. Once the tumor comes back after chemoradiation, it becomes more difficult to control," he says. "The IDH inhibitor is still going through the Food and Drug Administration (FDA) approval process, but we're optimistic it may be approved in the coming months."

Unlocking the immune system

Dr. Burns says the immune system can play a key role in destroying gliomas, but certain characteristics of glioma cells create obstacles. "It's been a challenge to focus the immune system on brain tumors because they look so much like the normal brain, and brain tumors specialize in suppressing the immune system," he says. "We're now performing clinical trials with combinations of immune therapies to ensure the immune system cells are activated and responsive against the tumor."

Immunotherapy may be more effective in some people than others. "Cancers outside the brain that have been most responsive to immunotherapies tend to have lots of mutations," says Dr. Burns. "There's some evidence that immunotherapy can be helpful for gliomas with a high number of mutations, but we’re pursuing several strategies to help the immune system find gliomas with fewer mutations."

Chimeric antigen receptor (CAR)-T cell therapy, which genetically modifies T cells in the immune system to activate, recognize and destroy certain cancers, has previously had limited uses for solid tumors like gliomas. Dr. Quiñones-Hinojosa says this could soon change. "We're beginning to devise therapies like CAR-T cell therapy at Mayo Clinic to hopefully have a better prognosis for our patients."

Preventing recurrence

Dr. Burns says evidence shows radiation can induce senescence, a process in which aged cells stop dividing but don't die, making it possible for tumors to recur. This could present an opportunity. "If the tumor cells are senescent after radiation, does that mean we could repurpose some of the emerging senolytic drugs that kill senescent cells to eradicate residual latent tumor cells?"

Mayo Clinic researchers are launching a clinical trial to help answer this question. "We recently received FDA approval to perform the first clinical trial of senolytic drugs in latent glioma — after patients have completed chemotherapy and radiation — in an attempt to prevent the tumor cells from coming back," says Dr. Burns.

Another clinical trial at Mayo Clinic explores using ultrasound technology to destroy tumor cells and potentially prevent recurrence. "We're using ultrasound in combination with a fluorescent dye called 5-ALA that is activated by ultrasound to kill tumor cells," says Dr. Burns. “The strategy is called sonodynamic therapy, and it's still in the early phases of clinical testing, but looks quite promising."

Dr. Quiñones-Hinojosa emphasizes that people's willingness to be part of ongoing research can help researchers find new therapies that will ultimately help patients. This can be as easy as allowing researchers to study tumor tissue that would have otherwise been discarded. "This allows us to bring this tissue to the laboratory to create avatars to study their disease," he says. Dr. Burns says some brain tumor patients are now volunteering to have a reservoir implanted under the scalp at the time of surgery, which allows researchers to follow biomarkers from cerebrospinal fluid over time. "This provides an incredibly valuable window into tumor biology as it evolves in response to therapy. It can provide real-time intelligence from behind enemy lines."

"Research gives people hope," says Dr. Quiñones-Hinojosa. "Sometimes just letting patients know they're part of something larger allows them to feel this emotion that can be much more powerful than fear."

Learn more

Learn more about glioma and find a glioma clinical trial at Mayo Clinic.

Join the Brain Tumor Support Group on Mayo Clinic Connect, an online community moderated by Mayo Clinic for patients and caregivers.

Also, read these articles:

• Clinical trials: A significant part of cancer care
• Mapping cell behaviors in high-grade glioma to improve treatment
• Defying all odds and exploring a remarkable journey beyond diagnosis
• Learn about meningioma and glioblastoma brain tumors
• 5 reasons brain tumors are still treated with radiation therapy
• Mayo Clinic expert describes 3 common brain tumors and their treatment