A Crystal Ball for Brain Cancer?
Reported August 03, 2009
(Ivanhoe Newswire) UCLA researchers have uncovered a new way to scan brain tumors and predict which ones will shrink when treated by the drug Avastin — before the patient ever starts treatment. By linking high water movement in tumors to positive drug response, the UCLA team predicted with 70 percent accuracy which patients’ tumors were the least likely to grow six months after therapy.
Bronnie McNabb, 57, considers himself a lucky man. When his aggressive brain cancer returned after chemotherapy and radiation, his UCLA doctor prescribed the off-label use of Avastin, a drug known to quell cancers in the breast, colon and lung. One month later, McNabb’s tumors had shrunk by 95 percent. Subsequent brain scans showed no trace of his cancer at all. The former marathon runner, ordained minister and father of two says he hasn’t felt this good since his diagnosis last winter.
It was welcomed news for patients like McNabb when the U.S. Food and Drug Administration approved the use of Avastin last month for the treatment of brain cancer. The powerful drug shrinks tumors by choking off their blood supply. About half of patients don’t respond to the therapy, however, exposing them to unnecessary side effects and medication costing up to $10,000 per month.
Now UCLA scientists have discovered a way to image tumors and forecast which patients are most likely to benefit from Avastin before starting a single dose of treatment.
“Avastin is an expensive drug, yet only 50 percent of patients with recurring brain cancers respond to it,” lead author Dr. Whitney Pope, assistant professor of radiological sciences at the David Geffen School of Medicine at UCLA is quoted as saying. “Until now, there has been no good way to identify these patients in advance. Our work is the first to suggest that we can predict which tumors will respond before the patient ever starts therapy.”
Pope and his colleagues focused on glioblastoma, the most common and deadly form of adult brain tumor, striking 12,000 Americans a year. Despite surgery, radiation and chemotherapy, the average glioblastoma patient lives only 12 to 15 months after diagnosis. Survival rates drop even lower if the tumor returns. Conventional therapies produce little benefit; only 8 to 15 percent of patients survive without tumor growth six months after treatment.
The UCLA team studied 82 patients who had undergone surgery and radiation therapy to remove glioblastoma. Half of the patients received infusions of Avastin every two weeks. All underwent monthly brain scans by magnetic resonance imaging (MRI) to monitor change.
Researchers analyzed the MRI scans of the patients whose tumors returned. Cancer cells secrete a growth factor called VEGF that spurs the growth of new blood vessels to supply the tumor with oxygen and nutrients. Avastin blocks VEGF, essentially starving the tumor to death.
This process launches a chain of events that is detectable by MRI. Oxygen-starved cells produce more VEGF, which causes blood vessels to leak fluids into the tumor and surrounding tissue. This results in swelling, which boosts water’s ability to move freely in the tumor and brain tissue. As cells disintegrate, they no longer pose a physical barrier to water movement.
“We theorized that tumors with more water motion would also have higher VEGF levels,” explained Pope. “Because Avastin targets VEGF, it made sense that the drug would work better in tumors with high levels of the growth factor.”
“When we realized that high levels of VEGF are linked to greater cell death and increased water movement, we were able to predict the patients’ response to Avastin before they began treatment,” explained Pope. “We were correct 70 percent of the time. Previously, identifying which patients would respond was like flipping a coin. This is a huge improvement.”
SOURCE: Radiology, August 2009