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The Ins and Outs of Glioblastoma From Standard of Care to Breakthrough Treatments for Brain Tumor Patients

Professor Mitchel S. Berger, MD, Director of the UCSF Brain Tumor Center

In the United States this year, neuro-oncologists will diagnose about 18,000 new brain tumors. One-third to half of these new patients will have high-grade tumors such as glioblastoma (GBM), anaplastic astrocytoma, or oligodendroglioma. Depending on the location and size of the tumor, in most of these patients the symptoms present as headaches, seizures, weakness in one side or the other, or difficulty with vision or language. These indicators are often the first sign that something is amiss, and usually suggest advanced disease because there are no current protocols for brain cancer screening at any age.

The standard of care for brain tumors depends on tumor grade and location but is typically a combination of radiation and chemotherapy, which come with a myriad of negative side effects. Higher-grade tumors are typically treated with radiation and chemotherapy and lower-grade tumors are typically treated with surgery. If a tumor falls into what surgeons or doctors consider good risk categories, it is simply observed.

Adding to the complexity of diagnosing and treating brain tumors is their notorious rate of recurrence. With high-grade tumors such as glioblastomas, at least 80-90 percent of them come back. With low-grade tumors, depending on the success of initial tumor removal, about 50 percent come back within the first ten years, with 60-70 percent of these recurring by twenty years post-surgery.

From a healthcare perspective, high-grade brain tumors such as glioblastoma are challenging to treat because there are few available options beyond the standard of care. Once radiation and chemotherapy approaches have been exhausted, there are clinical trials that patients can enroll in to try experimental treatments. These patients often face challenges in that they are very sick and are less likely to tolerate complicated or invasive procedures well. This is why I believe we need to have treatments that are less invasive or non-invasive that we can perform without putting medically fragile patients through surgery or complicated regimens.

Fortunately, new treatments for recurrent and primary GBM are providing new hope for brain tumor patients. Experimental therapies fall into a few different classes. First are targeted therapies, which are specifically developed and given to patients based on whether or not genetic sequencing of the tumor indicates they have a target for treatment. Other therapeutic strategies are immune based, intended to stimulate the immune system to destroy the tumor or overcome immune suppression. Another treatment strategy relies on viruses to specifically target and kill the tumor, but none of these experimental technologies have significantly moved the needle for GBM patients. With many different genomic and immunotherapy and viral therapy clinical trials taking place across the United States and around the world, I’m hopeful that we will learn much more about the biology of brain tumors and combinations of treatments that may be effective in managing disease progression.

A highly innovative and novel approach to treating high grade gliomas involves focused ultrasound. Focused ultrasound uses ultrasonic energy to target tissue deep in the body without surgical incisions or radiation. With a drug called delta aminolevulinic acid (ALA) that preferentially targets the tumor cells, physicians can use ultrasound in a very tuneable fashion to excite the drug, creating toxic metabolites that destroy the tumor cells without harming normal cells. This is a very phenomenal approach for a couple of reasons. The first is that a drug given orally or intravenously, in combination with focused ultrasound would be very minimally invasive and not require recovery time from surgery. Second, it would allow oncologists to repeatedly treat patients with the drug-ultrasound combination without harsh side effects. Third, it might potentially be used at the time of diagnosis to eventually replace chemo or radiation, and may be amenable to working with an appropriate immunotherapy or combination of therapies. All of these things could come into play. This is a radically different, innovative strategy that is exciting neurosurgeons like me because we can give the drug/ultrasound combination noninvasively in an outpatient setting. With this strategy, we can cover a wide area of the brain that may have infiltrating tumor cells, and we can use the well-tolerated drug that gets picked up by tumor cells and destroys them by focused ultrasound.

Focused ultrasound is certainly having a moment in oncology, and innovative approaches like sonodynamic therapy are appealing to patients largely because it is non-invasiveness and can be delivered in outpatient settings. A treating physician can perform this treatment in an hour or two, without going into the operating room, or without putting patients in a treatment center where they need to be closely monitored for adverse reactions. Sonodynamic therapy, if found to be as effective as its promise, will be a win-win for patients and doctors alike in the fight against glioblastoma and other high grade brain tumors.

August 12, 2021 at 6:30:00 AM


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