Neurosurgeons at Allegheny General Hospital (AGH) are exploring use of a drug that illuminates brain tumor cells to determine if the experimental visualization technique will enhance their ability to surgically excise tumors and improve patient survival.
AGH is one of just three medical centers in the country approved by the U.S. Food and Drug Administration to investigate the efficacy of an oral fluorescent compound, called 5-aminoevulnic acid (ALA), in a clinical trial of patients diagnosed with a glioma, the most common form of primary brain tumor.
Gliomas strike an estimated 10-12 thousand people each year in the United States and vary in severity. High grade gliomas, such as glioblastoma multiforma, are rapidly progressive and fatal malignant tumors. Low grade gliomas are more treatable, but also pose a risk of becoming cancerous overtime.
Regardless of grade, however, removing as much of a glial tumor as possible is critical to the patient's outcome, said Matthew Quigley, MD, director of AGH's Division of Neurosurgical Oncology.
"The nature of gliomas is such that regardless of the extent of surgery, some tumor cells will remain in the brain. Nevertheless, one of the few things we can do to improve somebody's survival from this disease is to perform as complete a tumor resection as possible. We know that patients who have a clean post-operative MRI tend to live longer," said Dr. Quigley, who is the hospital's co-lead investigator in the study of ALA with Khaled Aziz, MD, Director of AGH's Center for Complex Skull Base Surgery.
According to Dr. Aziz, gliomas are particularly challenging to resect because the infiltrative nature of the malignant cells produces indistinct borders between normal and diseased tissue.
"These tumors are often difficult because the lack of easily identifiable tumor margins under normal, direct vision of the operating field confounds the surgeon's attempts toward total resection. Any technique that would enhance our ability to more precisely determine these margins could make a significant difference for the patient," Dr. Aziz said.
"That is why we are so excited about investigating ALA as an adjunct to our conventional surgical approach. The preliminary experience with this innovative procedure has been extremely promising."
5-aminolevulinic acid is a compound that is converted into a fluorescent substance called photoporphyrin when it enters glioma tumor cells. The conversion does not occur in normal tissue. Thus under blue ultra-violet light conditions, the tumor appears as red.
After administering an oral dose of ALA to patients about three hours prior to surgery, surgeons use a modified surgical microscope that incorporates ultra-violet blue light to see the glowing tissue and guide their excision of the tumor.
In Germany, where ALA has already been approved for use in brain surgery, researchers have shown significant benefits associated with the therapy.
Reporting in The Lancet (Lancet Oncol. 2006 May; 7(5): 392-401), a team from the Heinrich-Heine University in Dusseldorf, Germany showed that nearly twice as many patients receiving fluorescence-guided surgery had their tumors completely removed as assessed by post-operative MRI scan, compared to those who received conventional surgery under white light.
Additionally, six months after surgery, 41 percent of those in the ALA treatment group had no progression of their tumor compared to 21 percent of those receiving conventional surgery. Though not designed to reliably measure overall survival, the study did not demonstrate a statistically significant difference between the two groups.
Still, Dr. Quigley said even extending lives by three or four months is progress in a group for whom time is so precious.
"Our goal in treating some who receives this devastating diagnosis is to do everything we can to maximize the quantity and quality of time they have left," Dr. Quigley said.
While the German studies focused primarily on high grade gliomas, Dr. Quigley said the AGH clinical trial will also explore ALA therapy in patients with low grade gliomas, where there is currently little data. The hospital has enrolled 12 patients in the study to date and has approval from the FDA to treat a total of 50 patients.
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