Resecting the Whole Tumor
UH neurosurgeons attack malignant brain tumors with advanced imaging technology and an experimental agent
Glioblastoma multiforme (GBM), a deadly malignancy that accounts for 23 percent of all primary brain tumors, poses a number of challenges to neurosurgeons as they attempt to eradicate all visible traces of malignant tissue. The borders of this highly invasive tumor can be notoriously difficult to discern. The tumor may be situated in an area of eloquent cortex, where surgery can pose a risk to adjacent normal tissue controlling speech or motor function. The tumor – and even the brain itself – can shift position in the course of surgery, hampering navigation that is based on preoperative imaging.
Despite these hurdles, it is critical that the surgeon remove as much of the glioma as possible, because current research indicates that extent of resection is one of the key factors affecting length of survival for patients with GBM, according to Andrew Sloan, MD, Director, University Hospitals Neurological Institute Brain Tumor and Neuro-Oncology Center; holder of the Peter D. Cristal Chair in Neurosurgery, and Associate Professor, Neurological Surgery, Case Western Reserve University School of Medicine. “There’s some variation among different studies, but it’s been shown that if you can get 90 to 95 percent of the tumor, or more, the patient will live 50 to 100 percent longer than if you leave more than 10 percent of the tumor,” says Dr. Sloan. “We never intentionally leave tumor behind except on very rare occasions when there’s involvement of an eloquent cortex, like speech or motor fibers.”
Fluorescence-Guided Resection
As part of a multifaceted approach to eradicating the tumor, Dr. Sloan and his colleagues are testing at University Hospitals Case Medical Center an orally administered compound, 5-aminolevulinic acid (5-ALA), that causes malignant gliomas to fluoresce pink when viewed under blue light. Fluorescence does not occur in adjacent normal tissue. Though widely used in Europe, the drug has not been approved by the U.S. Food and Drug Administration for this application. University Hospitals Case Medical Center is one of only a few U.S. centers testing the drug, according to Dr. Sloan. This surgical trial is funded by philanthropic donations to Dr. Sloan.
“This is the standard of care in Europe for the treatment of GBMs,” notes Dr. Sloan. “The doctors there feel strongly that 5-ALA is extremely valuable in helping them determine the borders of the tumor.” While the common practice in Europe is to discern the pink malignant tissue visually using only the blue light, Dr. Sloan takes the procedure a step further by using a fiber-optic probe that detects fluorescence not visible to the human eye. “Normally, the surgeon looks at the tumor under the blue light and subjectively decides whether the tissue he sees is pink or not pink,” he explains. “We and others have found that even when the surgeon can’t discern the color, the fluorescence still exists, and that suggests that this technique is more powerful than the human eye. If something is slightly fluorescent I may be able to see it, but there comes a point when I can no longer differentiate a low level of fluorescence from normal tissue. The fiber-optic probe can. When I touch it to the tissue, I actually get a waveform that I can quantify in various increments far more sensitive than my eye.”
Interpreting the data from the fiber-optic probe is a work in progress, Dr. Sloan says. “Generally, we think that if something is very fluorescent, say 100 units on an arbitrary scale, it’s tumor. If it’s 50 units, it’s probably still tumor. If it’s five or less, the question becomes, is it a small amount of infiltrated tumor, or is it inflammatory response? We understand this better with each successive case. We’re trying to better understand how to quantitate fluorescence and what each level of fluorescence means.”
Intraoperative Imaging
Complementing the use of 5-ALA in GBM surgery at UH Case Medical Center is state-of-the-art imaging technology that allows the surgeon to make “course corrections” during the procedure and minimize the likelihood that follow-up surgery will be needed to remove residual tumor. “Our navigation is based on how the MRI looks prior to surgery,” explains Dr. Sloan. “But particularly for a big, soft tumor, once you get into it, it starts to shift and the brain starts to shrink and change its position, and sometimes even the best surgeon might miss a little tumor.”
Previously, if a postoperative MRI showed a significant amount of residual tumor, the patient would undergo follow-up surgery. Now, at University Hospitals Case Medical Center, intraoperative MRI (iMRI) allows the surgeon to scan the tumor site before the patient is taken to recovery. “The patient’s head is open. We put on a special sterile coil so we don’t have to worry about infection, and we get the MRI,” says Dr. Sloan. “The beauty is that the MRI goes directly to my stereotactic computer and helps me navigate. I don’t have to go exploring; I just follow the MRI to the tumor and take it out. Now it’s not a second operation, with concomitant risks of infection and bleeding – it’s just a single operation with two parts.”
Andrew Sloan, MD
Director, University Hospitals Neurological Institute
Brain Tumor and Neuro-Oncology Center
Peter D. Cristal Chair in Neurosurgery
Associate Professor, Neurological Surgery
Case Western Reserve University School of Medicine.
Email Dr. Sloan for consultation.