New magnetic resonance analysis reveals brain tumor response to anti-angiogenesis therapy

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A new way of analyzing data acquired in magnetic resonance (MR) imaging appears to identify whether or not tumors are responding to anti-angiogenesis therapy. This information can help physicians determine the most appropriate treatments and discontinue ones that are ineffective.

The technique, called vessel architectural imaging (VAI), was able to identify changes in brain tumor blood vessels within days of initiation of anti-angiogenesis therapy.

"Until now the only ways of obtaining similar data on the blood vessels in patients' tumors were either taking a biopsy, which is a surgical procedure that can harm the patients and often cannot be repeated, or PET scanning, which provides limited information and exposes patients to a dose of radiation," said lead author Kyrre Emblem, PhD, of the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) in Boston. "VAI can acquire all of this information in a single MR exam that takes less than two minutes and can be safely repeated many times."

Previous studies in animals and in human patients have shown that the ability of anti-angiogenesis drugs to improve survival in cancer therapy stems from their ability to "normalize" the abnormal, leaky blood vessels that usually develop in a tumor, improving the perfusion of blood throughout a tumor and the effectiveness of chemotherapy and radiation. In the deadly brain tumor glioblastoma, the investigators found that anti-angiogenesis treatment alone significantly extends the survival of some patients by reducing edema, the swelling of brain tissue. In the current report, published in Nature Medicine (2013; doi:10.1038/nm.3289), the MGH team uses VAI to investigate how these drugs produce their effects and which patients benefit.

Advanced MR techniques developed in recent years can determine factors like the size, radius, and capacity of blood vessels. VAI combines information from two types of advanced MR images and analyzes them in a way that distinguishes among small arteries, veins, and capillaries, and it determines the radius of these vessels and shows how much oxygen is being delivered to tissues.

The MGH team used VAI to analyze MR data acquired in a phase 2 clinical trial of the anti-angiogenesis drug cediranib in patients with recurrent glioblastoma. The images had been taken before treatment started and then 1, 28, 56, and 112 days after it was initiated.

In some patients, VAI identified changes reflecting vascular normalization within the tumors–particularly changes in the shape of blood vessels–after 28 days of cediranib therapy and sometimes as early as the next day. Of the 30 patients whose data was analyzed, VAI indicated that 10 were true responders to cediranib, whereas 12 who had a worsening of disease were characterized as nonresponders. Data from the remaining eight patients suggested stabilization of their tumors.

Responding patients survived 6 months longer than nonresponders, a significant difference because the expected survival is less than two years, Emblem noted. He added that quickly identifying those whose tumors don't respond would allow discontinuation of the ineffective therapy and exploration of other options.

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