Vessel Architectural Imaging Reveals Glioblastoma Response to Antiangiogenesis Therapy

In their report published online in August 2013 in the journal Nature Medicine, investigators from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH; Boston, USA) described how their technology, called vessel architectural imaging (VAI), was able to detect changes in brain tumor blood vessels within days of the initiation of antiangiogenesis 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 [positron emission tomography] scanning, which provides limited information and exposes patients to a dose of radiation,” stated Kyrre Emblem, PhD, of the Martinos Center, lead and corresponding author of the report. “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.”

Earlier research in both animal and in human patients have shown that the ability of antiangiogenesis agents to improve survival in cancer therapy stems from their ability to “normalize” the abnormal, leaky blood vessels that typically develop in a tumor, improving the perfusion of blood throughout a tumor and the success of radiation and chemotherapy. In the lethal brain tumor disorder called glioblastoma, the researchers discovered that antiangiogenesis treatment by itself substantially extends the survival of some patients by lessening edema, the swelling of brain tissue. In the current report, the MGH researchers used VAI to examine how these agents produce their effects and which patients benefit.

Recently developed MRI techniques can determine factors like the size, radius, and capacity of blood vessels. VAI integrated data from two types of advanced MR images and analyzes them in a way that differentiates among veins, small arteries, and capillaries; determines the radius of these vessels and shows how much oxygen is being delivered to tissues. The investigators employed VAI to analyze MR data acquired in a phase 2 clinical trial of the antiangiogenesis 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 non-responders. Data from the remaining eight patients suggested stabilization of their tumors. Responding patients survived six months longer than non-responders, a considerable difference for patients with an expected survival of less than two years, Dr. Emblem reported. He also noted that rapidly identifying those whose tumors do not respond would allow discontinuation of the ineffective therapy and looking for other alternatives.

Gregory Sorensen, MD, senior author of the article, clarified, “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.” Formerly with the Martinos Center, Sorensen is now with Siemens Healthcare (Erlangen, Germany).

Study coauthor Rakesh Jain, PhD, director of the Steele Laboratory in the MGH department of radiation Oncology, added, “This is the most compelling evidence yet of vascular normalization with antiangiogenic therapy in cancer patients and how this concept can be used to select patients likely to benefit from these therapies.”

Lead author Dr. Emblem, noted that VAI may help further improve understanding of how abnormal tumor blood vessels change during antiangiogenesis treatment and could be useful in the treatment of other types of cancer and in 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 initiated, potentially eliminating treatment deemed to be ineffective.

Related Links:
Martinos Center for Biomedical Imaging at Massachusetts General Hospital