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Physiological/Biological Imaging Detects Response Earlier in Therapy than Standard CT/MRI Does

Fuerst, Mark

doi: 10.1097/01.COT.0000438514.57479.da

Specialized magnetic resonance imaging (MRI) tests can measure blood volume and cell density in brain tumors to determine whether clinical treatment is working, according to a new study.



“Physiological or biological imaging can assess tumor response to therapy earlier than anatomic imaging,” said Yue Cao, PhD, Professor of Radiation Oncology, Radiology and Biomedical Engineering and Head of the Functional Imaging Group at the University of Michigan, discussing data she presented at the American Association of Physicists in Medicine Annual Meeting.

“The conventional response to therapy is assessed months after therapy to evaluate tumor volume changes. If imaging tests indicate that a patient is not responding to therapy, a physician can alter treatment earlier, including intensifying therapy.”

Rather than waiting until after treatment to see if brain tumors have shrunk, doctors could use a specialized type of MRI during treatment to determine if it is working. In the study she reported, the team used dynamic contrast-enhanced MRI (DCE-MRI) imaging tests and diffusion-weighted MRI (DW-MRI)—which measure blood volume and cell density—to assess the response of brain tumors two weeks after radiation treatment.

Tumors that had decreased blood volume and cell density responded to therapy.

“Multi-modality imaging is needed to assess patient response and find out what is going on with the tumor,” Cao said. “Subvolumes of the tumor with high cell density—i.e., cellularity—and high blood volume—high neovascularity—can be detected by diffusion and perfusion imaging that could be predictive of response indicators.”

To gauge the success of treatment, patients typically undergo standard MRI or computed tomography (CT) imaging after therapy is completed, to determine whether or not the tumor has decreased in size. However, even when a treatment has worked, the tumor may not shrink for a month or more. “Even if a tumor is responsive to a treatment, its size looks similar on a CT scan or MRI for quite a while until the body starts to absorb the tissue,” Cao explained. “In the meantime, the patient has continued to undergo treatment that may not be working, therefore missing out on the opportunity to move on to a different or more powerful therapy.”



The researchers used DCE-MRI and DW-MRI to image the brains of 24 patients two weeks after starting radiation therapy to treat a total of 67 brain tumors. All 24 patients also had a standard MRI one month after treatment to determine if the tumors had shrunk. Both types of imaging revealed 24 tumors that showed decreases in density and/or abnormal blood volume two weeks after starting therapy, meaning that they had responded to therapy, which was confirmed by the one-month standard MRI.

After two weeks of therapy, we don't see much in the way of tumor volume changes, Cao continued. “If we look at the vascular level of the tumor, we can see minor changes—a 25 percent reduction in tumor size. If we look at the cellular level, cell density has decreased after two weeks.” She noted that the specialized imaging techniques have 90 percent accuracy in predicting tumor progression.

The research also reflects the reality that tumors themselves are not uniform, meaning that certain parts may respond to therapy while other parts do not. “Tumors are not homogenous. Some tumors have high cell density, and some have low cell density. We can probe the cell density with diffusion imaging,” she said. “Early on we can measure changes in vascular density, and that can tell us if the tumor is responding or not.”

The researchers used DCE-MRI to quantify additional information about the tumor, which could be used in the future to quickly assess whether treatment is working. If these findings bear out, MRI with perfusion and diffusion could be used to measure the effect of treatment earlier—for example, during therapy—instead of waiting until treatment has been completed.

“If even a portion of the tumor is not responding, that would signal clinicians to try more intensive therapy,” added another member of the research team, Christina Tsien, MD, Associate Professor of Radiation Oncology. “This approach could aid in the selection of a tumor or a subvolume of the tumor for intensified treatment after further validation.”

A related study by the same group showed that DCE-MRI can also measure early treatment response in liver tumors. Perfusion imaging can be enhanced in intrahepatic cancer as well, she said.

“We can predict progression months after completion of radiotherapy after 60 percent of the planned radiation dose. The technician could define the subvolume needed to treat more of the tumor. This potentially reduces toxicity and improves tumor control. We generally measure tumor response before therapy and at mid-point or after two-thirds of therapy has been delivered. We want to be as early as possible to change therapy, but give enough therapy to detect responses.”

The next step in the research will be to replicate the study and to show there is no increase in side effects, she said.

© 2013 by Lippincott Williams & Wilkins, Inc.
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