Laser Heat Therapy Combined with Immunotherapy Extends Survival in Brain Cancer Patients
A clinical trial combining laser interstitial thermal therapy with pembrolizumab shows nearly half of patients with recurrent high-grade astrocytoma alive at 18 months, compared to zero in the control group.
Patients with recurrent high-grade astrocytoma—an aggressive and typically fatal brain cancer—usually face a survival window of just four to five months. However, a groundbreaking clinical trial has demonstrated a massive leap in survival by combining Laser Interstitial Thermal Therapy (LITT) with the immunotherapy drug pembrolizumab.
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 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.
The study involved 45 patients with advanced-stage recurrent cancer, proving the combination is both safe and remarkably effective. 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.
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.
Researchers 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 cancer.