Breaking Barriers: New Treatment Extends Survival for Aggressive Brain Cancer
Recurrent high-grade astrocytoma, including glioblastoma, is an aggressive brain cancer with a typical survival of just four to five months. Immune checkpoint inhibitors, powerful tools that enable the immune system to target cancer cells, have historically been ineffective against these brain cancers due to the blood-brain barrier. Now, researchers at Keck Medicine of USC have identified a method to overcome this critical barrier, offering potential for extended patient survival.
Promising Clinical Trial Results Emerge
In a groundbreaking Phase 1/2b clinical trial, investigators explored a novel combination: laser interstitial thermal therapy (LITT) followed by the immune checkpoint inhibitor pembrolizumab. LITT, a minimally invasive procedure, utilizes laser heat to destroy tumor tissue and, crucially, disrupt the blood-brain barrier.
Key findings from the trial showcase remarkable improvements:
- Nearly half of patients treated with LITT followed by pembrolizumab were alive at 18 months. This stands in stark contrast to conventional treatment, where no patients receiving surgery followed by pembrolizumab survived at 18 months.
- Over one-third of patients who received LITT and the immune checkpoint inhibitor lived for more than three years, significantly surpassing the typical four-to-five-month survival for recurrent high-grade astrocytoma.
Dr. David Tran, chief of neuro-oncology at Keck Medicine and lead author of the study, emphasized the significance of these findings: "These results suggest LITT can enhance the effectiveness of pembrolizumab against high-grade astrocytoma, offering a new treatment option for patients with advanced cancer."
Understanding the Mechanism: Breaching the Blood-Brain Barrier
Previous research by Dr. Tran and his team laid the groundwork, indicating that LITT's precisely delivered heat can disrupt the blood-brain barrier for several weeks. This temporary disruption is critical, as it provides a sufficient window for T-cells—immune cells activated by drugs like pembrolizumab—to detect and target cancer cells within the brain.
During the trial, neurosurgeons utilized MRI to meticulously guide the LITT probe. This allowed for targeted delivery of laser heat, not only destroying tumor tissue but also strategically disrupting the blood-brain barrier.
The disruption serves a dual purpose: it enables tumor materials to enter the bloodstream, effectively alerting the body's T-cells to the presence of cancer. Simultaneously, it facilitates these activated T-cells' entry into the brain to launch a direct attack on the tumor.
Study Details and Safety Profile
The study included forty-five patients, all facing the challenging prognosis of their second or third recurrence of astrocytoma.
The combination of LITT and pembrolizumab was generally well-tolerated by participants and deemed safe. Both LITT and pembrolizumab have previously received FDA clearance or approval for various medical applications, underscoring their established safety profiles. The clinical trial was conducted across three prominent sites: Keck Medical Center of USC, Washington University in St. Louis, and the University of Florida.