Combined Laser Therapy and Immunotherapy Shows Promise for Aggressive Brain Cancer

A new treatment approach combining laser heat therapy with immunotherapy may dramatically improve survival for patients with recurrent high-grade astrocytoma, which includes glioblastoma. In a Phase 1/2b clinical trial, nearly half of patients treated with laser interstitial thermal therapy (LITT) followed by the immune checkpoint inhibitor pembrolizumab were still alive at 18 months, compared to none of the patients who received conventional surgery followed by pembrolizumab.

The results, published in Nature Communications, showed that 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. Patients with recurrent high-grade astrocytoma typically only survive for four to five months, making this potential extension of survival particularly significant.

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.

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, 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. Forty-five patients enrolled in the study, with all trial participants 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. The clinical trial was supported by a research funding and drug-provision grant from the biopharmaceutical company Merck and a research grant from Monteris Medical, a company providing LITT technology.

In separate research, scientists have discovered that steroids could make glioblastoma brain tumours vulnerable to a specially formulated diet. Steroids have been a vital part of glioblastoma care for more than 50 years, primarily to manage brain swelling and limit treatment side effects. Through a study published in Science Advances, researchers found that steroids dramatically alter how glioblastoma cells process vitamin B3 and an amino acid called methionine to make energy.

The steroids pushed the cells to set up new production lines for turning these ingredients into a specific metabolite that's rare in the rest of the brain. The metabolite identified (N1-methylnicotinamide) is about seven times more common in glioblastomas treated with steroids than in healthy brain cells. In mouse models, steroids combined with an experimental low-methionine diet safely halved methionine levels in glioblastoma cells and showed signs of restricting tumour growth.