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Glioblastoma Response to Antiangiogenesis Therapy Revealed via Vessel Architectural Imaging

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A new technique has been developed in order to successfully analyze information obtained in magnetic resonance imaging (MRI) that seems to be able to identify whether or not tumors are in fact responding to antiangiogenesis therapy.

In their report, researchers from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH; Boston, USA) explained how their new method called vessel architectural imaging (VAI), possessed the ability to distinguish changes in brain tumor blood vessels within days of the commencement of antiangiogenesis therapy.

Their findings have since been published online in August 2013 in the journal Nature Medicine.

“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 [positron emission tomography] scanning, which provides limited information and exposes patients to a dose of radiation. 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,” said lead and corresponding author of the report and member of the Martinos Center, Kyrre Emblem, PhD.

In the early stages of the research, both animals and human patients were able to demonstrate that the capability of antiangiogenesis agents to further enhance survival in cancer therapy comes from their ability to “normalize” the abnormal, leaky blood vessels that usually grow in a tumor, improving the perfusion of blood throughout a tumor and the success of radiation and chemotherapy.

In the fatal brain tumor disorder called glioblastoma, the researchers found that antiangiogenesis treatment on its own measure significantly prolongs the survival of some patients by reducing edema, which is the swelling of brain tissue. For their current report, the MGH researchers utilized VAI to inspect how this method could eventually produce their desired effects and identify which patients would benefit most from VAI.

Newly developed MRI methods can determine dynamics like the size, radius, and capacity of blood vessels. VAI incorporated data from two kinds of advanced MR images and analyzes them in a manner that is able to distinguish between veins, small arteries, and capillaries; determines the radius of these vessels and shows how much oxygen is being delivered to tissues. The researchers utilized VAI to analyze MR data obtained in a phase 2 clinical trial of the antiangiogenesis drug cediranib in patients with persistent glioblastoma. The images had been taken prior to the start of the treatment and then 1, 28, 56, and 112 days following its commencement.

In some patients, VAI managed to recognize changes representing vascular normalization within the tumors, principally changes in the shape of blood vessels following 28 days of cediranib therapy and sometimes as early as the very next day.

Of the 30 patients whose data was analyzed, VAI designated that 10 were true responders to cediranib, while 12 who had experienced a worsening of the disease were classified as non-responders. Data from the remaining eight patients suggested stabilization of their tumors. Responding patients survived six months longer than non-responders, a substantial difference for patients with an expected survival of less than two years, Emblem noted. He also pointed out that hastily recognizing those whose tumors do not respond would enable stoppage of the unsuccessful therapy and begin searching for other options.

“One of the biggest problems in cancer today is that we do not know who will benefit from a particular drug. Since only about half the patients who receive a typical anticancer drug benefit and the others just suffer side effects, knowing whether or not a patient’s tumor is responding to a drug can bring us one step closer to truly personalized medicine—tailoring therapies to the patients who will benefit and not wasting time and resources on treatments that will be ineffective.,” said senior author of the article, Gregory Sorensen, MD.

Emblem concluded that VAI may help further improve the understanding of how abnormal tumor blood vessels fluctuate during antiangiogenesis treatment and could be useful when observing the treatment of other kinds of cancer in other vascular conditions, like stroke. He and his colleagues are also exploring whether VAI can identify which glioblastoma patients are prone to respond to antiangiogenesis drugs even before therapy is started, possibly circumventing treatment regarded to be unsubstantial all together.

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