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New MRI Technique Reveals Brain Tumor Response to Antiangiogenesis Therapy

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Key Points

  • Researchers used vessel architectural imaging (VAI) to analyze magnetic resonance data acquired in a phase II clinical trial of cediranib in patients with recurrent glioblastoma.
  • Of the 30 patients analyzed, VAI indicated that 10 were true responders to cediranib. Responding patients ended up surviving 6 months longer than nonresponders, a significant difference.
  • In some patients, VAI identified changes reflecting vascular normalization within the tumors after 28 days of cediranib therapy and sometimes as early as the next day.

A new way of analyzing data acquired in magnetic resonance imaging (MRI) appears to be able to identify whether or not tumors are responding to antiangiogenesis therapy, which may help physicians determine the most appropriate treatments for patients. In a report published online in Nature Medicine, investigators from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) described how vessel architectural imaging (VAI) was able to identify 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 scanning, which provides limited information and exposes patients to a dose of radiation," said Kyrre Emblem, PhD, of the Martinos Center, lead and corresponding author of the report.  "VAI can acquire all of this information in a single MRI exam that takes less than 2 minutes and can be safely repeated many times."

Study Details

In previous reports, investigators at MGH found that antiangiogenesis treatment alone significantly extended the survival of some patients with glioblastoma by reducing edema.  In the current report, the research team used VAI to investigate how these drugs produce their effects and which patients benefit.

VAI combines information from two types of advanced magnetic resonance images and analyzes them in a way that distinguishes among small arteries, veins, and capillaries; determines the radius of these vessels; and shows how much oxygen is being delivered to tissues. The researchers used VAI to analyze magnetic resonance data acquired in a phase II clinical trial of the antiangiogenesis drug cediranib in patients with recurrent glioblastoma led by Tracy Batchelor, MD, Director of the Pappas Center for Neuro-Oncology at MGH and coauthor of the current paper. 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 8 patients suggested stabilization of their tumors.

Responding patients ended up surviving 6 months longer than nonresponders, a significant difference for patients with an expected survival of less than 2 years, Dr. 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.

One Step Closer to Personalized Medicine

Gregory Sorensen, MD, senior author of the report, explained, "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.”

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."

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 likely to respond to antiangiogenesis drugs even before therapy is initiated, potentially eliminating treatment destined to be ineffective.

Support for the study included grants from the U.S. Public Health Service, the National Cancer Institute, and other funders.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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