Originally published as JCO Early Release 10.1200/JCO.2007.15.4385 on July 14 2008

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Tumor Metabolism and Blood Flow Changes by Positron Emission Tomography: Relation to Survival in Patients Treated With Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer

Lisa K. Dunnwald, Julie R. Gralow, Georgiana K. Ellis, Robert B. Livingston, Hannah M. Linden, Jennifer M. Specht, Robert K. Doot, Thomas J. Lawton, William E. Barlow, Brenda F. Kurland, Erin K. Schubert, David A. Mankoff

From the Divisions of Nuclear Medicine and Medical Oncology and Departments of Bioengineering, Pathology, and Biostatistics, University of Washington; Seattle Cancer Care Alliance; and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Corresponding author: David Mankoff, MD, PhD, Division of Nuclear Medicine, MS G2-600, Seattle Cancer Care Alliance, 825 Eastlake Ave E, PO Box 19023, Seattle, WA 98109-1023; e-mail: dam{at}u.washington.edu

Purpose Patients with locally advanced breast carcinoma (LABC) receive preoperative chemotherapy to provide early systemic treatment and assess in vivo tumor response. Serial positron emission tomography (PET) has been shown to predict pathologic response in this setting. We evaluated serial quantitative PET tumor blood flow (BF) and metabolism as in vivo measurements to predict patient outcome.

Patients and Methods Fifty-three women with primary LABC underwent dynamic [¹⁸F]fluorodeoxyglucose (FDG) and [¹⁵O]water PET scans before and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and transport (FDG K₁) parameters were calculated; BF was estimated from the [¹⁵O]water study. Associations between BF, MRFDG, FDG K₁, and standardized uptake value and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model.

Results Patients with persistent or elevated BF and FDG K₁ from baseline to midtherapy had higher recurrence and mortality risks than patients with reductions. In multivariable analyses, BF and FDG K₁ changes remained independent prognosticators of DFS and OS. For example, in the association between BF and mortality, a patient with a 5% increase in tumor BF had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001).

Conclusion LABC patients with limited or no decline in BF and FDG K₁ experienced higher recurrence and mortality risks that were greater than the effects of clinical tumor characteristics. Tumor perfusion changes over the course of neoadjuvant chemotherapy measured directly by [¹⁵O]water or indirectly by dynamic FDG predict DFS and OS.

published online ahead of print at www.jco.org on July 14, 2008.

Supported in part by National Institutes of Health Grants No. CA72064, CA42045, and CA90771.

Presented in part at the 43rd American Society of Clinical Oncology Annual Meeting, June 1-5, 2007, Chicago, IL.

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

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