New technique 'lights up' brain tumor

Judy Morrill's husband noticed his wife seemed a little off last spring, but she insisted she felt fine.

But, Morrill, of North Royalton, Ohio, would forget to turn off the lights, or even the oven.

One day, when she was out with her friends, they noticed she was staring off into space and fiddling with her purse. They worried she was having a stroke, so Morrill, then 68, dutifully went to the ER.

To her great shock, the active grandmother was diagnosed with an aggressive brain tumor, called a glioblastoma.

“My birthday was a couple of weeks away, and I remember thinking, 'will I be here for my birthday?'” she recalled.

Morrill quickly had surgery to remove the tumor, but when she got home and began to read about the high mortality rate associated with glioblastomas—with treatment, patients survive an average of one to two years—she felt she needed a second opinion.

Morrill visited the Cleveland Clinic, where she enrolled in an experimental trial of a technique that allows surgeons to remove more of the tumor.

With glioblastomas, surgeons cannot remove the entire tumor because the edges get too close to important functional parts of the brain. Removing these parts could cause neurological problems  or “deficits.” Patients are treated with chemotherapy and radiation to kill remaining cancerous tissue.

But the more tumor they can get, the better.

At the Cleveland Clinic, her brain surgeon, Dr. Michael Vogelbaum, associate director of the Brain Tumor and Neuro-Oncology Center, used an experimental technique, which helps the surgeon see the tumor better and remove more of it.

Typically, surgeons use a contrast-enhanced MRI taken before the surgery to locate the tumor, but it is a static image and the brain may shift ever so slightly during surgery.

The goal of surgery is to remove all of tumor that lights up with the contrast on the MRI, but to avoid being overly aggressive and damaging an area of the brain that affects function.

“Visually, the part of the tumor at the edges sometimes may be indistinguishable from normal surrounding brain,”  Vogelbaum said.  So surgeons tend to err on the side of caution, leaving more of the edges intact.

In the experimental technique, two hours before surgery, a patient will drink a liquid that contains 5 ALA, a substance that causes the cancer cells to turn a fluorescent, pinkish-red color when exposed to blue light.

In Europe, a randomized trial found surgeons were able to remove more of the tumor when using 5 ALA and the more complete surgery was associated with a longer time for the tumor to recur.

The study found that 41 percent of those in the 5 ALA group had six months of progression-free survival, meaning that the tumor did not grow during that time, compared to 21 percent in those not treated with 5 ALA.

While 5 ALA is approved for use in Europe, the Food and Drug Administration has not approved it in the U.S.

“The FDA has asked the question, 'does the improved rate of resection [removal] improve survival to a meaningful degree?' And that we don’t know,” Vogelbaum said. “Some studies have strongly suggested this, but it’s not yet been proven,” he added.

The other issue is whether using 5 ALA will expose patients to more risk because the surgeon removes more tissue. When a German group of surgeons asked this question, they found an increased rate of new neurologic deficits after the surgery with 5 ALA, but these deficits resolved after a couple of months.

That suggests surgeons get closer to functional areas, disrupting function temporarily, but if careful, do not cause permanent neurological injury, Vogelbaum said.

“I figured, what have I got to lose?” she said. Her surgeon did in fact see more tumor that could be removed using 5 ALA.

Nearly a year later, her tumor has not progressed. Morrill said she feels great and is back to her active lifestyle.