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New imaging method gives early indication if brain cancer therapy is effective, U-M study shows

Diffusion MRI shows 3 weeks into treatment if tumor is responding --added 3/28/05

Ann Arbor - A special type of MRI scan that measures the flow of water molecules through the brain can help doctors determine early in the course of brain cancer regimen if a patient’s tumor will shrink, a new study shows.

brain tumor
Three dimensional representation of the functional diffusion map data in a patient with a malignant brain tumor at three weeks into a seven-week treatment schedule. Red and blue regions represent significant changes to the tumor cells early into treatment.

Researchers at the University of Michigan Comprehensive Cancer Center developed the assessment, which they call a functional diffusion map. They used a magnetic resonance imaging scan that tracks the diffusion, or movement, of water through the brain and mapped the changes in diffusion from the start of therapy to three weeks later. The tumor cells block the flow of water, so as those cells die, water diffusion changes.

In the study of 20 people with malignant brain tumors, the researchers found that any change in the functional diffusion map predicted 10 weeks before traditional techniques if the tumor was responding to the chemotherapy or radiation therapy. This has potential to spare patients from weeks of a grueling treatment regimen that’s not working and gives doctors the opportunity to switch patients early on to a therapy that may be more effective. Results of the study appear the week of March 28 in the early online edition of the Proceedings of the National Academy of Sciences.

Most primary brain tumors have a high mortality rate, with people surviving only 10 months after diagnosis. Typically, patients receive seven weeks of treatment, followed by a traditional MRI scan six weeks after completing therapy to determine if the tumor shrank. If the cancer did not respond to the treatment, a new approach may be tried.

Using diffusion MRI and the functional diffusion map, the U-M researchers were able to predict with 100 percent accuracy after only three weeks of treatment whether the therapy would be effective – 10 weeks before traditional methods would show a response.

no response tumor tumor responding to treatment
Two different brain tumor patients with functional diffusion maps overlayed on top of anatomical images three weeks into treatment. The patient on the left was called clinically unresponsive to treatment 10 weeks later. The novel functional diffusion map approach revealed a lack of change at three weeks (evidenced by very little changes in tumor cellularity - red and blue regions). The patient on the right was determined to be very responsive to treatment at 10 weeks later and the functional diffusion map approach detected huge tumor response as reflected by the large amount of red regions within the tumor mass at three weeks into therapy.

“This is an important issue in terms of patient quality of life. Do you want to go through seven weeks of treatment only to find two months later that it had no effect? Using MRI tumor diffusion values to accurately predict the treatment response early on could allow some patients to switch to a more beneficial therapy and avoid the side effects of a prolonged and ineffective treatment,” said Brian Ross, Ph.D., professor of radiology and biological chemistry at the U-M Medical School and a member of the U-M Comprehensive Cancer Center.

In the study, 20 participants with brain tumors underwent diffusion MRI before beginning a new treatment involving chemotherapy, radiation therapy or a combination. Three weeks later, they had another diffusion MRI. After finishing their treatment, the participants underwent standard MRI to determine whether their tumor responded to the therapy.

After three weeks – more than two months before the final MRI scan – researchers found significant differences between the patients’ scans. Some areas reflected an increase in water diffusion, suggesting tumor cell death; other areas saw a decrease in diffusion, which Ross said could be accounted for by the swelling some cells undergo before dying; and in some participants, researchers saw no change in diffusion.

“In the end, we found if the diffusion changes in any way, up or down, it correlates to a positive outcome. The magnitude or amount of change relates to the effectiveness of treatment. This indicates a different mixture of cell death pathways within the tumors. In the end, any change is good. When you think about it, if the treatment is not having an effect, the tumor will continue to grow without any change to water diffusion,” Ross said.

The researchers found that for each of the 20 patients, a change in the diffusion MRI accurately predicted the tumor’s response. Researchers plan to test the technique with breast cancer and head and neck cancer.

In addition to Ross, U-M study authors are Bradford Moffat, Ph.D., assistant professor of radiology; Thomas Chenevert, Ph.D., professor of radiology; Theodore Lawrence, M.D., Ph.D., Isadore Lampe Professor and Chair of Radiation Oncology; Charles Meyer, Ph.D., professor of radiology; Timothy Johnson, Ph.D., adjunct assistant professor and assistant research scientist in biostatistics; Qian Dong, M.D., a radiology fellow; Christina Tsien, M.D., lecturer in radiation oncology; Suresh Mukherji, M.D., associate professor of radiology; Douglas Quint, M.D., professor of radiology; Stephen Gebarski, M.D., professor of radiology; Patricia Robertson, M.D., associate professor of neurology and of pediatrics and communicable diseases; Larry Junck, M.D., professor of neurology; and Alnawaz Rehemtulla, Ph.D., associate professor of environmental health sciences, radiation oncology and radiology.

Funding for the study was from the National Cancer Institute and the Charles A. Dana Foundation.

The functional diffusion map is not yet available for routine use in clinic. A turn-key workstation capable of computing a diffusion map must be developed and approved by the U.S. Food and Drug Administration. The University of Michigan holds a patent on this MRI diffusion technology and has licensed the commercialization rights to Molecular Therapeutics, a corporation seeking to bring together several related technologies to create such a workstation. Ross, Rehemtulla and Chenevert, as inventors, would stand to benefit financially should the FDA approve this system and products result.

Patients seeking more information about brain cancer can call the Cancer AnswerLine™ at 800-865-1125, or visit www.cancer.med.umich.edu/learn/brain.htm.

Reference: Proceedings of the National Academy of Sciences, DOI 10.1073/pnas.0501532102

 

Written by: Nicole Fawcett

 

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