Originally published as JCO Early Release 10.1200/JCO.2007.15.2363 on June 9 2008

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Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival

Daniel A. Hamstra, Craig J. Galbán, Charles R. Meyer, Timothy D. Johnson, Pia C. Sundgren, Christina Tsien, Theodore S. Lawrence, Larry Junck, David J. Ross, Alnawaz Rehemtulla, Brian D. Ross, Thomas L. Chenevert

From the Departments of Radiology, Radiation Oncology, Neurology, and Biostatistics; and the Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan

Corresponding author: Thomas L. Chenevert, PhD, University of Michigan, B2A209 UH 1500 East Medical Center Dr, Ann Arbor, MI 48109-0030; e-mail: tlchenev{at}umich.edu

Purpose: Assessment of radiologic response (RR) for brain tumors utilizes the Macdonald criteria 8 to 10 weeks from the start of treatment. Diffusion magnetic resonance imaging (MRI) using a functional diffusion map (fDM) may provide an earlier measure to predict patient survival.

Patients and Methods: Sixty patients with high-grade glioma were enrolled onto a study of intratreatment MRI at 1, 3, and 10 weeks. Receiver operating characteristic curve analysis was used to evaluate imaging parameters as a function of patient survival at 1 year. Both log-rank and Cox proportional hazards models were utilized to assess overall survival.

Results: Greater increases in diffusion in response to therapy over time were observed in those patients alive at 1 year compared with those who died as a result of disease. The volume of tumor with increased diffusion by fDM at 3 weeks was the strongest predictor of patient survival at 1 year, with larger fDM predicting longer median survival (52.6 v 10.9 months; log-rank, P < .003; hazard ratio [HR] = 2.7; 95% CI, 1.5 to 5.9). Radiologic response at 10 weeks had similar prognostic value (median survival, 31.6 v 10.9 months; log-rank P < .0007; HR = 2.9; 95% CI, 1.7 to 7.2). Radiologic response and fDM differed in 25% of cases. A composite index of response including fDM and RR provided a robust predictor of patient survival and may identify patients in whom RR does not correlate with clinical outcome.

Conclusion: Compared with conventional neuroimaging, fDM provided an earlier assessment of equal predictive value, and the combination of fDM and RR provided a more accurate prediction of patient survival than either metric alone.

published online ahead of print at www.jco.org on June 9, 2008.

Supported by Grants No. PO1CA85878, PO1CA59827, 1P01CA87634, R24CA83099, and P50CA93990 from the National Institutes of Health and the National Cancer Institute.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.