Summary: 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 tria has demonstrated a massive leap in survival by combining Laser Interstitial Thermal Therapy (LITT) with the immunotherapy drug pembrolizumab.
The laser heat not only destroys tumor tissue but also temporary “unseals” the blood-brain barrier, allowing cancer-fighting T-cells to rush in and attack. The results were stunning: nearly half of the treated patients were still alive at 18 months, compared to zero in the control group.
Key Facts
- The Survival Leap: Nearly 50% of patients receiving the laser + immunotherapy combo were alive at 18 months; more than one-third survived beyond three years.
- Breaking the Barrier: The heat from LITT disrupts the blood-brain barrier for several weeks, providing a critical window for immunotherapy to reach the brain—a feat previously deemed nearly impossible.
- T-Cell Activation: The treatment allows tumor material to slip past the barrier and into the blood, “alerting” the immune system’s T-cells to the presence of the cancer.
- Minimally Invasive: The LITT procedure uses MRI guidance to precisely deliver heat to the tumor, sparing healthy brain tissue.
- Phase 1/2b Success: The study involved 45 patients with advanced-stage recurrent cancer, proving the combination is both safe and remarkably effective.
Source: USC
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 today 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, PhD, 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.
Other USC authors for the study include Son B. Le, PhD, assistant professor of research neurological surgery at the Keck School of Medicine of USC; Harshit Manektalia, MS, computational research scientist at the Keck School; and Dongjiang Chen, MD, assistant professor of research neurological surgery at the Keck School.
Key Questions Answered:
A: Brain cancer is notoriously hard to treat because the “blood-brain barrier” acts like a high-security wall that keeps medications out. This study found a way to “knock down the wall” using laser heat, allowing the body’s own immune system to finally see and attack the tumor.
A: The trial specifically targeted “high-grade astrocytoma,” which is one of the most aggressive and recurrent forms of brain cancer. Because both LITT and the drug pembrolizumab are already FDA-cleared for other uses, this combination could potentially become a new standard of care very quickly.
A: The LITT procedure is minimally invasive and uses real-time MRI to make sure the heat only hits the tumor. In the study, the combination was found to be generally well-tolerated by patients, even those in their second or third recurrence of cancer.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this brain cancer research news
Author: Gabbi Robison
Source: USC
Contact: Gabbi Robison – USC
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial” by Jian L. Campian, Son B. Le, Ashley Ghiaseddin, Omar H. Butt, Harshit Manektalia, Dongjiang Chen, Yifei Xu, Jingxia Liu, Maryam Rahman, Nathan Thai, William A. Leidig, Tanner Johanns, George Ansstas, Alice Y. Zhou, Sangami Pugazenthi, Gavin P. Dunn, Jiayi Huang, Milan G. Chheda, Albert H. Kim, Eric C. Leuthardt & David D. Tran. Nature Communications
DOI:10.1038/s41467-026-69522-w
Abstract
Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial
Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response.
A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose.
The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed by pembrolizumab (LITT + PEM) or non-LITT surgery followed by pembrolizumab (NLS + PEM). Phase 2’s primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, and immune signature.
After 21 patients, based on an independent Data and Safety Monitoring Committee request of unscheduled interim review of accumulating efficacy data, randomization stopped as benefit from NLS + PEM appeared limited, and the subsequent 24 patients received LITT + PEM.
The pre-specified study endpoints were achieved. Among 39 per-protocol patients, LITT + PEM (n = 33) improved median OS (11.8 versus 5.2 months) and 18-month survival (42% versus 0%) compared to NLS + PEM (n = 6) (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06–0.49; P = 0.0002). Median PFS was longer in LITT + PEM (4.5 versus 1.6 months; HR 0.21; 95% CI, 0.08–0.56; P = 0.0006). In an intent-to-treat sensitivity analysis (n = 21), OS (HR 0.29; 95% CI, 0.10–0.88) and PFS (HR 0.30; 95% CI, 0.10–0.87) again favored LITT + PEM (n = 13).
Treatment was well tolerated. LITT activated non-classical monocytes, and pembrolizumab unleashed CD8⁺ T cell proliferation, clonal expansion, and coordinated memory T-cell responses. Overall, LITT + PEM is safe and may overcome rHGA immunosuppression to generate antitumor immunity.
