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Radiology

New brain imaging technique helps predict patients’ response to Avastin

10/20/2010

CU-Brain ImagingGlioblastoma is the most common and deadly type of primary brain tumor in adults. On average, glioblastoma patients survive only 12 to 15 months after initial diagnosis despite conventional treatment with surgery, chemotherapy and radiation.The prognosis for patients with recurrent gliobastoma is worse. Food and Drug Administration (FDA) approval of the drug Avastin represented the first new systemic therapy shown to be effective against recurrent glioblastoma in more than 10 years, but the majority of patients with recurring brain tumors do not respond to the drug. Using magnetic resonance imaging (MRI) of the brain, UCLA scientists have developed a way to predict which glioblastoma patients are most likely to benefit from Avastin – before the patient takes a single dose.

Avastin is significant treatment advance, but most glioblastoma patients don’t respond

Avastin is a molecularly targeted therapy that neutralizes vascular endothelial growth factor (VEGF), a chemical signal that stimulates the growth of new blood vessels needed to supply tumors with oxygen and nutrients. In a multi-center randomized clinical trial, Avastin – alone and in combination with the chemotherapy drug CPT-11 – increased response rates (nearly 40 percent with Avastin compared to 5 percent with conventional therapies) and significantly improved progression-free survival rates in patients with recurrent glioblastomas. Half as many patients experienced tumor growth after six months of treatment with Avastin as did patients receiving conventional therapies. Avastin is generally well-tolerated, enables patients to avoid the toxic side effects of chemotherapy and often makes it possible to reduce steroids and minimize related side effects (weight gain, fluid retention, mood swings, increased risk of infection, increased blood pressure, bone calcium loss). Still, progression-free patients with recurring glioblastomas do not respond to the drug, which may cost up to $10,000 per month. Additionally, some researchers hypothesize that Avastin may make tumors more aggressive and resistant in some patients.

Using MRI to predict Avastin response with 70 percent accuracy

Avastin works by blocking the VEGF secreted by cancer cells. When cancer cells produce increased amounts of VEGF to stimulate angiogenesis (blood vessel growth), fluids leak into the tumor and surrounding tissue and cause swelling and increased water motion in the tumor. In a controlled clinical study, UCLA researchers measured these changes using MRI in a sample of 82 patients with recurrent glioblastoma. The team found that tumors with more water motion, which they hypothesized corresponded to higher VEGF levels, responded best to Avastin. This discovery allowed the scientists to predict with 70 percent accuracy in which patients the tumors would continue to progress within six months. The team published their findings in Radiology (July 2009) and are testing the technique in two, larger clinical trials. The researchers also plan to investigate their ability to increase their predictive accuracy and to identify which glioblastoma patients will respond to Avastin before the tumor is removed surgically. With information from these studies, patients and their physicians will be equipped to make more informed decisions about which therapies to avoid or pursue.

First published study predicting glioblastoma patients’ response to Avastin is key to tailored medicine

“Tumors are different genetically and metabolically,” says Whitney Pope, M.D., Ph.D., assistant professor of radiological sciences at the David Geffen School of Medicine at UCLA. “There are many drugs being developed for glioblastoma that work by different mechanisms, and it is important to match each patient with the drug that is most likely to help them.” Dr. Pope and his UCLA colleagues published the first ever study specifically attempting to predict which patients with recurrent glioblastoma would respond to Avastin. Using MRI to measure structural changes in the tumors of patients who received targeted treatment with Avastin, the team of UCLA scientists predicted with 70 percent accuracy whether or not the drug would be effective. The goal, Dr. Pope says, is tailored medicine.

“If we can achieve even higher predictive accuracy, we can design the best therapy to fight the tumor as well as improve each patient’s quality of the life,” Dr. Pope says.

Participating Researchers

Whitney Pope, M.D., Ph.D
Assistant Professor, Radiological Sciences
David Geffen School of Medicine at UCLA

Timothy Cloughesy, M.D.
Professor and Director
Department of Neurology
David Geffen School of Medicine at UCLA

Paul Mischel, M.D.
Professor, Department of Pathology
and Laboratory Medicine
David Geffen School of Medicine at UCLA

Albert Lai, M.D., Ph.D
Assistant Professor
Department of Neurology
David Geffen School of Medicine at UCLA Phioanh Leia Nghiemphu, M.D. Assistant Professor Department of Neurology David Geffen School of Medicine at UCLA

Syed Rahmanuddin, M.D.
Research Assistant
David Geffen School of Medicine at UCLA

Jonathan Goldin, M.D.
Professor, Radiological Sciences
David Geffen School of Medicine at UCLA

Contact Information
Whitney Pope, M.D., Ph.D.
Assistant Professor
Radiological Sciences
David Geffen School of Medicine at UCLA
10833 Le Conte Ave.
BL-428, CHS
Los Angeles, CA 90095
(310) 206-3545 Voice
(310) 825-2776 Fax
wpope@mednet.ucla.edu





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