Laser heat therapy plus immunotherapy may dramatically improve survival for those with deadly brain cancer

Glioblastoma (histology slide). Credit: Wikipedia/CC BY-SA 3.0

High-grade astrocytoma, which includes glioblastoma, is a fast-growing, aggressive brain cancer that often returns after the tumor is removed, making it difficult to treat. Patients with recurrent high-grade astrocytoma typically only survive for four to five months.

Immune checkpoint inhibitors, medications that allow the body’s own immune system, particularly cancer-fighting T-cells, to recognize, find and attack tumor cells, can help stop the recurrence of cancer in many parts of the body.

However, these drugs are not usually effective on brain cancers like astrocytoma due to the blood-brain barrier—a tightly sealed layer of cells that acts as a protective boundary between the brain and the bloodstream. Because this barrier is so effective, it also limits the ability of immune cells, including cancer-fighting T-cells, to enter the brain and reach the tumor.

But now, Keck Medicine of USC researchers may have discovered a way to break through this blood-brain barrier and make immune checkpoint inhibitors effective for patients with recurrent, high-grade astrocytoma, thus potentially extending patients’ lives.

Stunning results

In a Phase 1/2b clinical trial, investigators combined a minimally invasive procedure that uses laser heat to both destroy the tumor tissue and disrupt the blood-brain barrier, with a common immune checkpoint inhibitor drug, pembrolizumab.

The results, published in Nature Communications, were striking. Nearly half of patients treated with laser interstitial thermal therapy (LITT), followed by pembrolizumab were still alive at 18 months. In comparison, none of the patients who received a conventional treatment of surgery followed by pembrolizumab were alive at the 18-month mark.

In addition, more than one-third of patients treated with LITT and the immune checkpoint inhibitor lived more than three years, far exceeding the typical four-to-five-month survival for patients with recurrent high-grade astrocytoma.

“These results suggest that LITT can help the immune checkpoint inhibitor pembrolizumab work more effectively against high-grade astrocytoma,” said David Tran, MD, Ph.D., chief of neuro-oncology with Keck Medicine, co-director of the USC Brain Tumor Center and lead author of the study.

“Patients with this type of advanced cancer have few remaining options and poor outcomes, and this approach could meaningfully extend their survival time and provide new hope for patients and their loved ones.”

How LITT breaks through the blood-brain barrier

Tran and his colleagues based the study on their past research showing that the heat produced by LITT can disrupt the blood–brain barrier for several weeks, which is enough time for T-cells to detect and target cancer cells once they have been activated by an immune checkpoint inhibitor.

During the trial, participants received either LITT or surgery/biopsy, then the pembrolizumab. For those receiving LITT, neurosurgeons used magnetic resonance imaging (MRI) to locate the tumor in the brain, guide the LITT probe into the tumor, then precisely deliver laser heat to the tumor.

The heat destroys the tumor while surgeons work to ensure no healthy brain tissue is damaged; and as a side product, the heat disrupts the blood-brain barrier.

Once patients receive the immune checkpoint inhibitor, this disruption allows tumor materials to slip past the blood-brain barrier and into the blood. “This alerts T-cells to the presence of the tumor and provides easy passage of these T-cells to rush in, find and attack the tumor,” said Tran.

About the clinical trial

Forty-five patients enrolled in the study. All trial participants were in their second recurrence of astrocytoma, with nearly 15% in their third recurrence, meaning the cancer was at a very advanced stage.

The LITT plus pembrolizumab combination was found to be generally safe and well-tolerated.

Since the trial began, the U.S. Food and Drug Administration has cleared LITT for treating certain brain tumors, and pembrolizumab has been approved for several cancers.

Keck Medical Center of USC was one of the three clinical trial sites nationwide, alongside researchers from Washington University in St. Louis and the University of Florida.

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