Astrocytoma and glioblastoma are fast-growing brain cancers that often return after surgery, with survival for astrocytoma patients averaging only four to five months. While medications that activate the body’s immune system, particularly T-cells that fight cancer, successfully stop most recurring cancers, they have proven ineffective against brain cancers like astrocytoma. This is due to the blood-brain barrier (BBB), a tight layer of cells that acts as a protective barrier around the brain and bloodstream, blocking immune system access to tumor tissue.

Breaking Through the BBB

Researchers at USC Keck Medicine and three other sites nationwide have developed a breakthrough approach. In a Phase 1/2b clinical trial published in Nature Communications, investigators combined laser interstitial thermal therapy (LITT), a minimally invasive procedure, with pembrolizumab, an immune checkpoint inhibitor drug.

The treatment works by employing laser heat to achieve two simultaneous goals: destroying malignant tumor tissue and disrupting the BBB. This disruption temporarily opens the barrier, allowing T-cells to penetrate and target cancer cells. Dr. David Tran, the study’s lead author and neuro-oncology chief at USC, noted that this approach extends treatment options and longer-term survival for patients with limited alternatives.

Trial Results

The trial enrolled 45 patients with recurrent astrocytoma, approximately 15 percent of whom were experiencing their third relapse. During treatment, patients received either LITT or standard surgery/biopsy, followed by pembrolizumab. MRI guidance was used to precisely deliver laser heat to the tumor while protecting healthy brain tissue.

The results were significant: approximately half of patients who received LITT combined with pembrolizumab survived to the 18-month mark, and survivors experienced at least three years longer survival compared to the control group treated with standard surgery plus pembrolizumab.

Moving Forward

The combination of LITT and pembrolizumab was found to be safe and well tolerated. The FDA has cleared LITT for treating various brain tumors, while pembrolizumab has received approval for certain cancers. This novel combination represents a promising new treatment option for patients with recurring high-grade astrocytoma.