High-grade astrocytoma, which includes glioblastoma or GBM, is a fast-growing, aggressive, typically fatal, brain cancer that often returns after initial treatment. Treatment options are limited, focusing on managing symptoms and slowing progression, often involving repeat surgery, radiotherapy, and chemotherapy. The disease is difficult to treat, and patients diagnosed 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 prevent cancer recurrence in many parts of the body. However, due to the blood-brain barrier, a tightly sealed layer of cells designed to protect the brain from the bloodstream, these drugs are generally not effective against brain cancers such as astrocytoma. Because the blood-brain 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.
Now, for the first time, researchers at Keck Medicine of the University of Southern California (USC), alongside researchers from Washington University in St. Louis and the University of Florida, may have discovered a way to break through the blood-brain barrier and make immune checkpoint inhibitors effective for patients with recurrent, high-grade astrocytoma, potentially extending patients’ lives.
Stunning results
In a Phase 1/2b clinical trial (NCT02311582), supported by research funding and drug-provision from Merck & Co/MSD and a research grant from Monteris Medical, investigators combined a minimally invasive procedure that uses laser heat to both destroy the tumor tissue and disrupt the blood-brain barrier, with pembrolizumab, a common immune checkpoint inhibitor drug.
The results, published inthe February 26, 2026 edition of Nature Communications, were striking.[1] Nearly half of patients treated with laser interstitial thermal therapy (LITT), also known as Stereotactic Laser Ablation (SLA), a minimally invasive cytoreductive approach, followed by pembrolizumab (Keytruda®; Merck & Co/MSD), were still alive at 18 months.* [2] 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.
A study analysis demonstrates that the combination of LITT and pembrolizumab is safe and well-tolerated, and delivers an overall survival advantage of more than 3-fold compared to surgery or biopsy plus immunotherapy.
“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,” Tran added.
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.
Video: Orin Block, M.D., FAANS, Director, UC Davis Brain Tumor Program; Professor, Department of Neurological Surgery, presents case studies following patient selection and treatment with Laser Interstitial Thermal Therapy (LITT) for brain tumors at the September 2025 Monteris NeuroBlate Surgeon Forum.
During the trial, participants received either LITT or surgery/biopsy, then 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, and 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,” Tran explained.
Study design
The study enrolled forty-five patients. Most participating patients were in their second recurrence of astrocytoma, with nearly 15% in their third recurrence, meaning the cancer was at a very advanced stage, limiting the overall patient’s health-related Quality-of-Life (hrQoL). The trial outcomes demonstrated that the combination of LITT and pembrolizumab was generally safe and well-tolerated.
Following the start of the trial, the U.S. Food and Drug Administration has cleared LITT, developed by Monteris Medical, for treating certain brain tumors, and has approved pembrolizumab for several cancers.
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Note: * Laser interstitial thermal therapy has recently gained prominence in the treatment of malignant primary and metastatic brain tumors. [2]
Clinical Trials
MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas – ClinicalTrials.gov ID NCT02311582
Highlights of Prescribing Information
pembrolizumab (Keytruda®; Merck & Co/MSD)[Prescribing Information]
Reference
[1] Campian JL, Le SB, Ghiaseddin A, Butt OH, Manektalia H, Chen D, Xu Y, Liu J, Rahman M, Thai N, Leidig WA, Johanns T, Ansstas G, Zhou AY, Pugazenthi S, Dunn GP, Huang J, Chheda MG, Kim AH, Leuthardt EC, Tran DD. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun. 2026 Feb 26;17(1):1763. doi: 10.1038/s41467-026-69522-w. PMID: 41748622; PMCID: PMC12946167.
Featured image courtesy © 2018 – 2026 Fotolia/Adobe. Used with permission.
DOI
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