MRI Identifies Responses to Antiangiogenesis Treatment

In a retrospective analysis of data from patients with recurrent glioblastomas, researchers found that a new MRI technique they've named vessel architectural imaging (VAI) rapidly identifies how tumor blood vessels responded to antiangiogenic therapy.

The study shows how VAI MR data could be used to better customize a cancer patient's treatment, says Kyrre Emblem, PhD, a medical physicist at the Martinos Center for Medical Imaging at Massachusetts General Hospital (MGH) in Boston, lead author on a study published in Nature Medicine. Emblem also conducts research at Oslo University Hospital in Norway.

The new imaging technique may distinguish between patients who respond favorably to a given drug and those who don't much earlier in the treatment process than conventional techniques, says Emblem. Patients who don't respond to a given drug might benefit from changing treatment.

“With conventional contrast-enhanced MRI, you might have to wait for weeks or months before you see a patient's response to therapy,” says Emblem. “Our data suggest that with VAI, you can identify within a few days or a week patients who respond or don't respond to therapy.”

VAI may also help explain the mechanisms underlying antiangiogenic therapy. The technique analyzes the size and integrity of macroscopic and microscopic blood vessels, with associated estimates of oxygen saturation levels, using data from two types of MRI readouts that are collected simultaneously. With the right software, centers with MRI machines can employ VAI using existing resources, says Emblem.

The researchers analyzed data collected from 30 patients with recurrent glioblastomas from a phase II clinical trial of the antiangiogenesis drug cediranib (AstraZeneca). VAI identified patients whose vasculature responded to treatment by normalizing the vessel branching structure and oxygen saturation levels within the tumor, the scientists say. Their analysis indicated 10 patients whose vessels responded favorably to the drug, 8 patients whose tumors stabilized, and 12 patients with worsening disease.

Previously, the researchers found that patients who responded to cediranib treatment by boosting blood flow within the tumor survived roughly six months longer than patients who did not boost response.

Angiogenesis inhibitors were initially believed to starve tumors by impeding the growth of new blood vessels. More than a decade ago, Rakesh Jain, PhD, tumor biologist at MGH and Harvard Medical School in Boston, postulated that the drugs also work by “normalizing” abnormal and leaky blood vessels within tumors, thereby decreasing permeability and increasing circulation. (Jain is also coauthor on the VAI paper.) When the vessels' architecture resembles that of healthy vessels, according to this hypothesis, vascular permeability also may be normal, so that drugs may more effectively move through the vascular bed to treat the tumor.

The new VAI study offers evidence in the theory's favor, suggests Emblem. He notes, however, that potential mechanisms for antiangiogenic therapy remain the focus of much research and debate.