High-grade astrocytoma, which includes glioblastoma,\u00a0is a fast-growing, aggressive\u00a0brain cancer\u00a0that often returns after the tumor is removed, making it difficult to treat.\u00a0Patients\u00a0with recurrent\u00a0high-grade astrocytoma\u00a0typically only survive for\u00a0four to five months.\u00a0<\/p>\n
Immune checkpoint inhibitors,\u00a0medications\u00a0that allow the body’s own immune system,\u00a0particularly\u00a0cancer-fighting\u00a0T-cells, to recognize, find and attack tumor cells,\u00a0can help stop the recurrence of cancer\u00a0in many parts of the body.\u00a0<\/p>\n
However,\u00a0these drugs\u00a0are not\u00a0usually\u00a0effective\u00a0on brain cancers like astrocytoma\u00a0due to\u00a0the\u00a0blood-brain barrier –\u00a0a\u00a0tightly sealed layer of cells that acts as a protective boundary between the brain and the bloodstream. Because this barrier is so effective, it also\u00a0limits the ability of\u00a0immune cells, including\u00a0cancer-fighting\u00a0T-cells, to enter the brain and reach the tumor.\u00a0<\/p>\n
But now,\u00a0Keck Medicine of USC\u00a0researchers may have discovered a way to\u00a0break\u00a0through\u00a0this\u00a0blood-brain barrier and\u00a0make immune checkpoint inhibitors effective for patients with recurrent, high-grade astrocytoma,\u00a0thus\u00a0potentially extending patients’ lives.\u00a0<\/p>\n
Stunning results\u00a0<\/p>\n
In a Phase 1\/2b clinical trial,\u00a0investigators\u00a0combined\u00a0a minimally invasive procedure that uses laser heat to\u00a0both destroy the tumor tissue and\u00a0disrupt the blood-brain\u00a0barrier, with\u00a0a common\u00a0immune checkpoint inhibitor drug, pembrolizumab.\u00a0<\/p>\n
The results, published\u00a0today\u00a0in\u00a0Nature Communications, were striking.\u00a0Nearly half\u00a0of patients treated with\u00a0laser interstitial thermal therapy (LITT),\u00a0followed by\u00a0pembrolizumab were\u00a0still\u00a0alive at\u00a018 months. In comparison, none\u00a0of the patients who received a conventional treatment of surgery followed by\u00a0pembrolizumab\u00a0were\u00a0alive at the 18-month-mark.\u00a0<\/p>\n
In addition, more than\u00a0one-third of patients treated with LITT and\u00a0the immune checkpoint inhibitor\u00a0lived more than three years,\u00a0far exceeding\u00a0the typical\u00a0four-to-five-month\u00a0survival for patients with recurrent high-grade astrocytoma.\u00a0<\/p>\n
<\/p>\n
These results\u00a0suggest\u00a0that LITT can help the immune checkpoint inhibitor pembrolizumab work more effectively against high-grade astrocytoma. Patients with this type of advanced cancer have few remaining options and poor outcomes,\u00a0and\u00a0this approach could\u00a0meaningfully extend\u00a0their\u00a0survival\u00a0time\u00a0and provide new hope for patients and their\u00a0loved ones.”\u00a0<\/p>\n
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<\/p>\n
David Tran, MD, PhD, chief of neuro-oncology with Keck Medicine, co-director of the\u00a0USC Brain Tumor Center\u00a0and\u00a0lead author of the study<\/p>\n
<\/p>\n
How LITT\u00a0breaks\u00a0through the\u00a0blood-brain barrier\u00a0<\/p>\n
Tran and his colleagues based the study on their\u00a0past research showing\u00a0that\u00a0the heat produced by\u00a0LITT can\u00a0disrupt the blood\u2013brain barrier for\u00a0several\u00a0weeks, which is enough time\u00a0for T-cells\u00a0to detect and target\u00a0cancer\u00a0cells once they have been activated by an\u00a0immune checkpoint inhibitor.\u00a0<\/p>\n
During the trial,\u00a0participants received\u00a0either\u00a0LITT or surgery\/biopsy<\/a>, then the pembrolizumab.\u00a0For those receiving LITT, neurosurgeons used\u00a0magnetic resonance imaging\u00a0(MRI)\u00a0to\u00a0locate\u00a0the tumor in the brain,\u00a0guide the LITT probe into the tumor, then\u00a0precisely\u00a0deliver\u00a0laser\u00a0heat to the tumor.\u00a0The\u00a0heat\u00a0destroys the tumor while surgeons\u00a0work to\u00a0ensure no healthy brain tissue is damaged;\u00a0and as\u00a0a side product,\u00a0the heat\u00a0disrupts the blood-brain barrier.\u00a0<\/p>\n Once patients receive the\u00a0immune checkpoint inhibitor,\u00a0this disruption\u00a0allows\u00a0tumor materials\u00a0to\u00a0slip past the blood-brain barrier and into the blood. “This alerts\u00a0T-cells to the presence of the tumor\u00a0and\u00a0provides\u00a0easy\u00a0passage of these T-cells to rush in,\u00a0find and attack the tumor,” said Tran.\u00a0<\/p>\n About the clinical trial\u00a0<\/p>\n Forty-five patients enrolled in\u00a0the\u00a0study.\u00a0All\u00a0trial participants\u00a0were in their second recurrence\u00a0of\u00a0astrocytoma,\u00a0with\u00a0nearly 15%\u00a0in their third recurrence, meaning the cancer was at a very advanced stage.\u00a0<\/p>\n The LITT plus pembrolizumab combination was\u00a0found to be\u00a0generally\u00a0safe\u00a0and well-tolerated.\u00a0<\/p>\n 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.\u00a0<\/p>\n Keck Medical Center\u00a0of USC\u00a0was one of\u00a0the three\u00a0clinical trial\u00a0sites\u00a0nationwide,\u00a0alongside\u00a0researchers from Washington University in St. Louis and the University of Florida.\u00a0<\/p>\n Other\u00a0USC\u00a0authors\u00a0for the study\u00a0include Son\u00a0B.\u00a0Le, PhD, assistant professor of research neurological surgery\u00a0at the\u00a0Keck School of Medicine of USC;\u00a0Harshit\u00a0Manektalia, MS, computational research scientist\u00a0at the Keck School;\u00a0and\u00a0Dongjiang\u00a0Chen,\u00a0MD,\u00a0assistant professor of research neurological surgery at the Keck School.\u00a0<\/p>\n Source:<\/p>\n University of Southern California – Health Sciences<\/a><\/p>\n Journal reference:<\/p>\n