Abstract of the Year No. 4: Preliminary Results of the FRONTIER Trial: Safety and Feasibility of Yttrium-90 TheraSphere in Recurrent Glioblastoma
Presentation: Wednesday, April 2, at 8 a.m.
Glioblastoma (GBM), an aggressive type of brain cancer, remains one of the most formidable challenges in oncology—but promising results from a new trial investigating the feasibility of yttrium-90 (Y-90) microsphere therapy may indicate a role for IR in the treatment of recurrent GBM.
Samdeep Mouli, MD, FSIR
The data come from the preliminary results of the FRONTIER Trial, a multicenter, multidisciplinary, first-in-man study evaluating the safety and feasibility of intra-arterial Y-90 microsphere therapy as an endovascular radiotherapy for patients with recurrent GBM.
Lack of options, poor outcomes
There are approximately 12,000 case sa year of GBM, according to lead researcher Samdeep Mouli, MD, FSIR. The median survival for patients is approximately 14 to 16 months, with a 5-year survival rate of less than 5%. According to Dr. Mouli, traditional therapies, such as surgical resection and external radiotherapy plus chemotherapy, have limited success.
“Pretty much every patient, after completing chemotherapy and external radiotherapy, experiences recurrence of disease. At that point, there is no standard of care,” Dr. Mouli said. At this stage, patients are often referred to clinical trials. Many chemotherapies and radiotherapies have been explored in the GBM space, Dr. Mouli said—though they come with many limitations in terms of response, safety and toxicity.
“We know radiation works in the brain and in tumors in general. However, due to the location of these tumors in the critical structures of the brain, there’s limitations on how much radiation a patient can receive before they suffer toxicity,” Dr. Mouli said. “With chemo, the blood brain barrier is difficult to manage, and so chemotherapy doesn’t penetrate the brain as well as it would in other organs. And with surgery, there is often substantial residual tumor left behind because the infiltrated nature of GBM extends beyond the borders of what we can see visually or on imaging.”
In light of these limitations, the new paradigm of delivering radiotherapy intra-arterially may be a viable path for a patient population that is otherwise out of options.
A new approach for Y-90 therapy
Y-90 microsphere treatment has long been established as an approved therapy for hepatocellular carcinoma (HCC) and has changed the management of complex HCC patients, bridging more patients to transplant and expanding curative options. However, the experience outside the liver is very limited, Dr. Mouli said, and while intra-arterial therapies have been explored in the brain before, the idea of injecting particles or microspheres into the brain was largely unheard of in the GBM space.
“The study was designed as a safety trial in this first group of patients with recurrent GBM to determine who would even be safe to undertake something like this,” Dr. Mouli said.
Because researchers had no data on how this therapy would work in humans, and the risks included ischemia, stroke and hemorrhage, the trial was designed to be similar to a stroke trial as well as an oncological trial. Patients were put through rigorous neurologic exams before and after therapy, and only patients with tumors in the non-eloquent, non-dominant hemisphere of the brain were selected for this initial trial.
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According to Dr. Mouli, of the eight patients who they have complete data for, all left the hospital the day after therapy with a stable neurologic exam and no change in their baseline function.
“What we found, similar to our liver experience, was a preferential uptake of the radiation dose within the tumors. Our target was 40 Gy, but the tumors actually saw up to 120 Gy within the tumor,” Dr. Mouli said. “So that was very favorable for what we were expecting.”
In half of the patients treated, Dr. Mouli’s team also saw a decrease in the size of the tumor on imaging after 1 month.
Improving quality of life
“It’s still early, but we’re very excited about the direction this is going,” he said. “The fact that we may be able to safely deliver radiotherapy intraarterially to patients who are otherwise out of options is very promising—as well as the fact that we can deliver radiation doses that exceed what is possible with external beam radiotherapy.”
In addition, patients noted positive quality of life outcomes immediately following the minimally invasive therapy.
“Compared to other therapies for these patients, like repeat surgical resection or chemo, patients tolerated this really well,” Dr. Mouli said. Not only were patients able to go home the next day, but they described a better experience than previous interventions and improved hospital experiences. “My patients were talking to their loved ones, Christmas shopping on their devices and making plans to go out to dinner. It was extremely heartwarming to see and very moving for everyone involved in the study.”
Next steps
Though this initial safety trial has shown promising results, there are still many more levels of research required, Dr. Mouli said.
“The most important thing is to make sure that everything we saw in this trial stays consistent amongst all patients in terms of imaging response and the primary endpoints of safety and neurologic findings,” he said. “Everyone—the oncologists and surgeons as well—are very excited about these findings, and the goal will eventually be to expand this to other areas of the brain. But we have to see what the data shows first.”
Dr. Mouli said he is grateful for the support of the multidisciplinary teams at the five sites who were part of the trial—especially as the role of IR in the treatment of GBM has previously been nonexistent.
“I think this study shows that not only is there a role for IR to work with multidisciplinary teams to care for these patients, but that in the future, IR may actually be integral to treating GBM.”
