Immunontherapy For Glioblastoma: Could It Be More Effective Before Surgery?

For patients facing tough brain tumors, treatment options have long been limited, and outcomes have remained difficult despite decades of research. But doctors are now exploring a different strategy that could begin to shift that reality.

WATCH: Hope for Glioblastoma Research

Why Immunotherapy Has Struggled

Immunotherapy has already transformed treatment for cancers like melanoma and lung cancer. But it hasn’t worked as well in glioblastoma, and there may be more than one reason why.

Glioblastoma is considered a “cold tumor,” meaning it doesn’t naturally trigger a strong immune response. In simple terms, the immune system has a harder time recognizing it as a threat.

Timing may also play a critical role.

By the time most patients receive immunotherapy, they’ve already undergone surgery, radiation, and chemotherapy—treatments that can weaken the immune system. These extra treatments can make it harder for immunotherapy to do its job effectively.

“By the time patients receive immunotherapy in later stages, they are often more immunosuppressed, and the likelihood of treatment working becomes smaller,” said Dr. Khasraw.

A New Approach: Treat Before Surgery

This clinical trial is testing a different approach:

• Give immunotherapy before the tumor is removed during surgery
• While the immune system can still “see” the cancer

Immunotherapy works by training the immune system to attack tumor cells. However, if the tumor is removed first, there may not be enough of it left to properly “teach” the immune system what to target the cancerous cells.

“Immunotherapy requires antigen exposure—it needs to be educated to understand what tumor proteins to attack,” said Dr. Mustafa Khasraw of Duke Cancer Institute. “If you remove the tumor first and then give immunotherapy, there’s less material to train the immune system.”

Why This Matters

This different approach to treating glioblastoma isn’t just about a new drug; it’s about developing a new strategy.

By treating patients earlier—before surgery and before the immune system is weakened by radiation or chemotherapy—doctors hope to give immunotherapy its best chance to work.

For patients, that could mean:

• A stronger, more effective immune response
• The possibility of slowing a disease that has long been difficult to treat
• Access to a promising treatment option at the earliest stage of care

Taking the Next Step

Clinical trials are how progress happens—especially in diseases like glioblastoma, where new options are urgently needed.

In the U.S., all new drugs must go through clinical trials before the U.S. Food and Drug Administration approves them. Although the rewards of clinical trials can be great, they also come with risks. Talking to your doctor about this before enrolling in a trial is important. Some risks to consider include:

• The risk of harm and/or side effects due to experimental treatments
• Researchers may be unaware of some potential side effects of experimental treatments
• The treatment may not work for you, even if it has worked for others

WATCH: Clinical trials can be life-saving.

Dr. Beth Karlan is a gynecologic oncologist at UCLA Health. She says the goal with clinical trials is to advance cancer research to a point where the disease becomes akin to diabetes, where it becomes a manageable condition.

“Clinical trials hopefully can benefit you, but they also provide vital information to the whole scientific community about the effectiveness of these treatments,” Dr. Karlan said.

“They can be life-saving. We’ve seen many in the last few years of children and adults who have participated in trials and have had miraculous results,” Dr. Karlan continued.

If you or a loved one has been recently diagnosed, it may be worth asking your care team about clinical trials like the one led by Dr. Kharsaw at Duke University Hospital.

Not every patient will be eligible. But for some, participating in a clinical trial can offer access to cutting-edge treatments and help advance science for future patients.

How to Find a Clinical Trial

If you want to participate in a clinical trial, your first step should be to talk with your doctor. They can address many of your initial questions and help you determine if you would make a good participant.

Another crucial part of clinical trials is finding the right one for you. SurvirorNet has a resource called the Clinical Trial Finder to help with this.

How Immunotherapy Works

Checkpoint inhibitors, such as the immunotherapy drug pembrolizumab (brand name: Keytruda), help the immune system do its job by removing the “invisibility cloak” that cancer cells use to hide.

Normally, a protein called PD-1 acts like a brake on T cells, keeping them from attacking healthy cells. But cancer takes advantage of that brake to avoid being targeted. Pembrolizumab blocks PD-1, releasing the brake and letting T cells go after cancer cells more aggressively—just like they’re meant to.

While immunotherapy is adequate for most patients, it has side effects, most of which are related to inflammation.

You might experience diarrhea when your colon is inflamed or itching when your skin is inflamed. You can also have pain in your liver or pancreas if you have pancreatitis or hepatitis.

RELATED: Immunotherapy in Recurrence

WATCH: Understanding immunotherapy side effects.

Common Immunotherapy side effects include:

• Fatigue
• Nausea or stomach discomfort
• Joint pain
• Diarrhea or constipation
• Cough
• Rash
• Loss of appetite
• Changes in blood cell counts
• Fever

More severe adverse reactions include:

• Pancreatitis: Inflammation of the pancreas
• Colitis: Inflammation of the large intestine
• Pneumonitis: Inflammation of the lungs
• Hepatitis: Inflammation of the liver
• Thyroiditis: Inflammation of the thyroid gland

If you experience severe side effects, your doctor may need to temporarily or permanently stop your immunotherapy treatment.

“The side effects of immunotherapy are not, quote, forever. Depending on the severity, it depends on how we manage it. Some patients will develop diarrhea, and we can give them treatments to help it subside after a couple of days. It might be sporadic over a couple of weeks,” Dr. Anna Pavlick, a medical oncologist at Weill Cornell Medicine, tells SurvivorNet.

Understanding a Glioblastoma Diagnosis

Diagnosing gliomas involves a multi-step approach that includes clinical assessment, imaging studies, histopathological examination, and molecular testing.

As patients are diagnosed, they’re observed for typical glioma symptoms. These may include:

• Headaches
• Seizures
• Cognitive or Behavioral Changes
• Visual or Speech Changes and Impairments
• Loss of Body Weight and Deconditioning
• Changes in mental function, mood, or personality
• Changes in speech
• Sensory changes in hearing, smell, and sight
• Loss of balance
• Changes in your pulse and breathing rate

During the clinical assessment, the physician will take a detailed history, focusing on the onset and progression of symptoms.

Since gliomas can present with non-specific symptoms that overlap with other neurological conditions, ruling out conditions like stroke, infections, or inflammatory disorders is essential during the initial clinical evaluation.

Patients then undergo a neurological exam that tests cranial nerve function, motor strength and coordination, sensory function, and cognitive abilities.

Next, patients undergo an MRI, which provides doctors with a visualization of the tumor.

“If you’re suspected of having a tumor on imaging and our neurosurgeons think that tumor can come out, they will take a piece of that tumor out first and confirm in the operating room and with our pathologists that, in fact, what they are looking at is a tumor,” Dr. Alexandra Miller, Director of the Neuro-Oncologist Division at NYU Langone Health, tells SurvivorNet. “And if it is, they resect it at that time. It’s not usually a two-step procedure.”

If surgery cannot be performed due to tumor location or patient-specific factors, a less invasive stereotactic biopsy can be obtained. Once the tissue sample is obtained, it’s examined under a microscope for molecular testing. At this stage, the tumor is given a grade, which determines how aggressive it is.

WATCH: Molecular testing for glioma patients

• Grade I-II gliomas – These are considered low-grade and tend to grow slowly. “The grade one is a very indolent, benign tumor that can be cured with surgery alone,” Dr. Henry Friedman, Deputy Director of the Preston Robert Tisch Brain Tumor Center at Duke, tells SurvivorNet.
• Grade III gliomas—These are considered high-grade and tend to grow more rapidly. They are typically classified as malignant and require more aggressive treatment, which can include surgery, radiation, and chemotherapy.
• Grade IV gliomas – These are the most aggressive gliomas, which are locally aggressive and require treatment intensification. Glioblastomas are the most common grade IV glioma, “which is by far the most well-known and feared tumor in the lay population and, quite frankly, the medical population,” Dr. Friedman explains.

Learn more about SurvivorNet's rigorous medical review process.

---