The Future of Brain Tumor Care is Being Built Now — at Siteman Cancer Center

WashU Medicine experts at Siteman’s Brain Tumor Center are accelerating the science that will create a new standard and new survivorship for brain tumor care

For years, progress against glioblastoma has been measured in small steps with only slight improvements in survival. Now, at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, bold research and remarkable advances against this deadliest form of brain cancer are driving real progress and offering new hope for patients and families.

“We’re at a turning point — a real transition point. We’re potentially on the cusp of breakthroughs over the next five years that we haven’t seen in decades,” said Gregory J. Zipfel, MD, the Ralph G. Dacey Distinguished Professor of Neurological Surgery and chair of the Taylor Family Department of Neurosurgery at WashU Medicine and a founding member of The Brain Tumor Center at Siteman Cancer Center. “But those breakthroughs aren’t going to come from a single discovery — they’re going to come from combining approaches that we are actively investigating and using here.”

Access to clinical trials and second opinion consults are available at The Brain Tumor Center by calling our Siteman care coordinators — oncology-trained nurses who help with scheduling and navigation — at 800-600-3606 or by requesting an appointment here.

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WashU Medicine physicians and scientists at Siteman Cancer Center are transforming brain tumor care through the relentless and imaginative pursuit of innovative science and research. Advances in research and clinical trials include developing groundbreaking artificial intelligence (AI) brain-mapping software, initiating groundbreaking radiation and immunotherapy clinical trials, and advancing the use of laser interstitial thermal therapy (LITT) to treat recurrent glioblastoma.

In 2021, Zipfel helped establish The Brain Tumor Center at Siteman Cancer Center, bringing together a team of influential neuro-oncologists, neurosurgeons, radiation oncologists and others focused on providing care attuned to the needs of each patient and aimed at improving lasting outcomes. Working together, the center’s translational researchers, who oversee clinical trials, and basic scientists are focused on creating even better treatment paradigms moving forward.

The Brain Tumor Center at Siteman is led by neurosurgeon Albert H. Kim, MD, PhD, the August A. Busch Jr. Professor of Neurological Surgery and senior vice chair of the Department of Neurosurgery at WashU Medicine. Associate directors are neuro-oncologist Milan G. Chheda, MD, associate professor of medicine and director of neuro-oncology, and radiation oncologist Jiayi Huang, MD, professor of radiation oncology and chief of the CNS/Gamma Knife Service, both also of WashU Medicine.

Other leaders of The Brain Tumor Center are:

• Research Director Alexander H. Stegh, PhD, who also is a professor of neurosurgery and vice-chair of neurosurgery research at WashU Medicine
• Caroline H. Ko, PhD, the center’s associate director of research strategy and clinical translation and an associate research professor of neurosurgery at WashU Medicine

 

Advancing Glioblastoma Treatment Through Translational Science

Even with surgery, chemotherapy and radiation, glioblastoma remains very difficult to treat. Average survival is 15-18 months after diagnosis. Because standard therapies are not curative, the tumor almost always returns.

“The problem isn’t always the main tumor,” Chheda explained. “It’s the microscopic cells that have already spread. Those are what cause recurrence.”

While the primary tumor may be visible and treatable, those microscopic cells often evade therapy. Many are resistant to chemotherapy and radiation. At the same time, the brain itself presents unique barriers. As with the normal brain, brain tumors remain shielded by the blood-brain barrier, a protective network of blood vessels and tissue that prevents entry of many drugs.

“The therapies we currently have are not always reaching the right place, and even when they do, they may not target the right cells,” Chheda said.

Overcoming the challenges of glioblastoma treatment requires more than a single breakthrough. At Siteman, physician-scientists are developing complementary strategies that target the disease from multiple directions — advancing discoveries that are already reshaping how brain tumors are studied and treated here and around the world.

 

Leaders in Laser Interstitial Thermal Therapy (LITT)

Eric C. Leuthardt, MD, MBA, the Shi H. Huang Professor of Neurological Surgery and vice chair of innovation in the Department of Neurosurgery at WashU Medicine, is a global leader in the research and use of laser interstitial thermal therapy (LITT) to treat glioblastomas and deep-seated brain tumors. He was one of the first in the country to use LITT for brain cancers when it was cleared by the federal Food and Drug Administration (FDA) in 2010. He has since refined the therapy for minimally invasive tumor ablation and helped to define the national patient criteria for its use.

Leuthardt, Kim and Zipfel are now advancing the use of MRI-guided LITT. A pioneering discovery found that LITT temporarily disrupts the blood-brain barrier, creating a window of opportunity of up to six weeks during which anti-tumor drugs can be used after tumor ablation. They also are investigating how adding checkpoint inhibitors, a type of immunotherapy, into the mix can also improve outcomes.

Research has found that LITT improves the length of survival by up to 40% for certain patients with recurrent glioblastoma. A highly specialized laser ablation surgical suite is now in regular use at Barnes-Jewish Hospital, and the team has performed several hundred LITT procedures, making it one of the busiest centers in the world.

 

Pioneers in Investigating the Link Between Brain Tumors and Aging

Chheda is rethinking how brain tumors form. Because glioblastoma predominantly occurs in older adults, he is investigating how the aging process itself contributes to brain tumor development.

“You could argue that with time, cells pick up mutations and eventually something goes wrong,” Chheda said. “But it’s also true that the brain itself changes as it ages.”

Instead of viewing glioblastoma as a disease caused by rogue cancer cells, it may also be influenced by changes in the surrounding tissue, called the tumor microenvironment. To Chheda, aging is not just a risk factor. It may also actively influence how tumors emerge, evolve and resist treatment.

“This is a relatively new and exciting area of research, and not many groups are focused on it yet,” he said. “We are exploring how aging alters the brain at a molecular level. By doing so, we may uncover new strategies that can prevent tumor formation, or at the very least, make other treatments more effective.”

 

Planning Underway for First-in-Human Clinical Trials Using Zika Virus

Ongoing in Chheda’s lab are groundbreaking studies with a modified version of the Zika virus that is engineered to kill glioblastoma. He and colleague Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and professor of molecular microbiology and of pathology and immunology at WashU Medicine, have confirmed that combining the modified Zika virus with standard immunotherapy drugs increased survival rates in mice, from 30% to nearly 90%. The researchers now have created a strain of Zika that is safe for use in humans.

“In mouse models, combining this approach of using Zika-based oncolytic viruses with immunotherapy makes previously ineffective treatments work,” Chheda said. Phase I first-in-human clinical trials are expected to begin before the end of 2026.

 

Sonobiopsy: Rapidly Advancing New Technology Discovered at Siteman

As multiple researchers explored ways to open the blood-brain barrier to allow for targeted therapies, a team led by Leuthardt and WashU bioengineer Hong Chen, PhD, a professor of biomedical engineering and of neurosurgery and a Siteman research member, invented an ultrasound technology that temporarily opens that barrier. Now called sonobiopsy, the technique uses focused ultrasound and microbubbles to open the blood-brain barrier, which then allows for a non-invasive “liquid biopsy” of the brain tumor, as well as opening the door to add anti-tumor drugs. A first-in-human clinical trial began in 2023 in select patients with high-grade gliomas, including glioblastoma, which originate in the brain or spinal cord.

“What’s remarkable about this is the speed of translation,” Kim said. “It moved from concept to human trials in about three to five years, much faster than normal, which is about a decade. It’s exciting and probably is one of the most significant technological advances coming out of The Brain Tumor Center at Siteman.”

 

The Most Advanced Radiation Research is Focused on Protecting the Brain

Radiation oncology research is focused on a fundamental challenge: delivering more effective treatment while preserving the healthy brain. Through investigator-initiated and national multicenter clinical trials, WashU Medicine radiation oncologist Jiayi Huang, MD, and colleagues are evaluating innovative approaches designed to improve tumor control, reduce injury to normal tissue and help patients maintain cognitive function throughout treatment. Huang leads pioneering radiation oncology clinical trials that are showing promise in treating glioblastoma.

He is the principal investigator of a multicenter, randomized Phase III clinical trial comparing temporally modulated pulsed radiation therapy (TMPRT) to standard radiotherapy in patients with a type of recurrent glioma, including glioblastomas. TMPRT divides radiation into small pulses with short breaks in between rather than giving radiation to the patient all at once. Early studies found that TMPRT improved survival and preserved cognitive function and memory. The current large-scale study is funded by the National Cancer Institute and conducted through NRG Oncology, one of five national research groups in the NCI’s National Clinical Trials Network. The goal is to enroll almost 400 patients in the Phase III trial over the next four years.

“We think it will control the tumor spread better,” Huang said, “and also cause less injury to normal tissue and less cognitive deficit in patients.”

He is also testing the combination of radiation with an oral agent to enhance immune responses in patients with glioblastoma. Based on his own early-phase investigator-initiated trial, it is hoped that immune-modulating radiation will improve survival. Already, the therapy is moving toward testing in newly diagnosed brain cancer patients later this year.

In a collaboration between neurosurgeons and radiation oncologists, Huang points to the excitement surrounding an industry-led clinical trial that uses radiation seeds implanted into a foam tile that is then placed directly into the brain during surgery to remove a tumor. Called GammaTile, it functions much like the more well-known radiation seeds for prostate cancer.

“The seed itself is not new, and it can move if you insert it into the brain separately,” Huang explained. “Using the seed-implanted foam keeps the seeds in one location to better direct the radiation.”

 

First Vaccine and Other Innovative Therapies for Glioblastoma

Another major effort involves the development of personalized vaccines tailored to each patient’s brain tumor. A key discovery was that different regions of a tumor can have different mutations. As a result, current clinical trials now sample multiple tumor regions and target shared mutations, improving the effectiveness of treatment options.

Exciting and promising news came just this spring, after an early-stage clinical trial co-led by WashU Medicine researchers at Siteman Cancer Center found that a personalized vaccine to treat glioblastoma is safe and resulted in robust and broad immune responses. The responses appear to increase recurrence-free survival in a subset of patients after surgery.

“We are extremely encouraged by these results,” said lead author Tanner M. Johanns, MD, PhD, assistant professor of medicine at WashU Medicine and a Siteman research member. “This kind of vaccine is a first for glioblastoma, and it is exciting to think how we can leverage this individualized therapeutic DNA cancer vaccine platform to make a positive impact on the lives of patients who are fighting this disease.”

While directly delivering medicines to the brain remains extremely challenging, Stegh and his team have developed a novel drug delivery method that can cross the blood-brain barrier and activate the immune system to attack glioblastoma.

Their technology uses precisely engineered structures assembled from nano-size materials to deliver potent tumor-fighting medicine to the brain through nasal drops. This method is less invasive than similar treatments in development and was shown to be effective in mice. The researchers are now working toward a first-in-human clinical trial.

“This redefines how cancer immunotherapy can be achieved in otherwise difficult-to-access tumors,” Stegh said.

 

Global Leaders in Advancing Pediatric Brain Tumor Care

In addition to researching effective treatments for adults with brain cancers, The Brain Tumor Center at Siteman has been at the forefront of advancing targeted therapies for children diagnosed with certain types of brain tumors.

WashU Medicine’s Eric M. Thompson, MD, chief of pediatric neurosurgery at Siteman Kids at St. Louis Children’s Hospital, is exploring the effectiveness of a new targeted therapy called moxetumomab pasudotox for children whose brain tumors have not responded well to standard treatment options.

Mohamed Abdelbaki, MD, director of the pediatric brain tumor program at WashU Medicine and Siteman Kids, is investigating another experimental therapy, ONC-212. The tailored therapy attacks cancer cells at the molecular level.

The pediatric brain tumor program at Siteman Kids at St. Louis Children’s Hospital is recognized globally. Abdelbaki founded and leads an international pediatric brain tumor board that comprises experts from around the world who meet regularly to review difficult brain cancer cases. The tumor board has rapidly become the leading consortium of experts committed to collaborative, multidisciplinary discussions that inform recommendations for pediatric brain cancer treatment.

“These studies ensure that innovation in brain tumor care and research reaches patients at every stage of life,” Zipfel said.

 

One of the Nation’s Most Advanced Brain Tumor Centers

The Brain Tumor Center at Siteman Cancer Center brings together one of the nation’s most comprehensive programs in brain tumor research and care, integrating neurosurgery, neuro-oncology, radiation oncology, advanced imaging, artificial intelligence and translational science to accelerate discovery and improve patient outcomes. That collaborative model is driving innovations ranging from FDA-approved, real-time brain-mapping technology used during surgery to machine learning tools that help predict tumor growth, guide surgical planning and personalize care after treatment.

“Our environment is built for discovery,” said Jiayi Huang, MD. “The Brain Tumor Center and the WashU Jeffrey T. Fort Neuroscience Research Building bring together neurosurgeons, radiation oncologists, physician-scientists and basic researchers in ways that accelerate new ideas into new treatments. That level of collaboration is what distinguishes Siteman and WashU Medicine.”

Albert H. Kim, MD, PhD, director of The Brain Tumor Center, says the program’s scale strengthens both patient care and scientific discovery. Each year, the multidisciplinary team performs more than 700 brain tumor surgeries and cares for approximately 2,000 new patients while training the next generation of surgical and medical neuro-oncology specialists.

“Our goal is not simply to advance today’s standard of care,” Kim said. “It’s to define what the next standard should be.”

WashU Medicine science writer Mark Reynolds contributed to this report.