Dose-Dependent Effects of Radiation Therapy on Cerebral Blood Flow, Metabolism, and Neurocognitive Dysfunction
Received 12 November 2007; received in revised form 21 May 2008; accepted 22 May 2008. published online 27 August 2008.
Purpose
A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors.
Methods and Materials
Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment. Analyses were performed for correlations between changes in 2-deoxy-2-[18F]-fluoro-d-glucose (FDG)-PET (metabolism), 15O-PET (relative blood flow), regional radiation dose, follow-up time, and neuropsychological test scores.
Results
Eleven subjects were enrolled and 6 completed follow-up studies. The PET data showed reduced FDG uptake, with average decreases of 2–6% in regions of the brain receiving greater than 40 Gy at 3 weeks' and 6 months' follow-up. The 15O-H2O PET showed increases (<10%) at 3 weeks in relative regional blood flow in brain receiving greater than 30 Gy, but less at the 6-month follow-up studies. There were significant correlations between decreases in FDG uptake and increased scores from the Symptom Checklist-90-R, with an average increase in T score of 2 (p < 0.0001). The Wisconsin Card Sorting Test showed a significant correlation of decreased FDG uptake with increased errors and perseveration in test performance, with an average decrease in T score of 11 (p = 0.037).
Conclusions
A dose-dependent response of CNS tissue was detected using FDG PET in this small number of patients. Decreases in CNS metabolism correlated with decreased performance on neuropsychological tests for problem solving, cognitive flexibility, and global measures of psychopathology. Additional research is needed to verify and define these findings.
∗Department of Radiation Oncology, Duke University Medical Center, Durham, NC
†Department of Radiology, Duke University Medical Center, Durham, NC
‡Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC
§Duke Cancer Center Biostatistics, Duke University Medical Center, Durham, NC
¶21st Century Oncology/Southern New England Regional Cancer Center, Woonsocket, RI
Reprint requests to: Carol A. Hahn, M.D., Department of Radiation Oncology, Duke University Medical Center, Box 3085, Durham, NC 27710. Tel: (919) 668-7336; Fax: (919) 668-7345
Data presented at the CURED II Meeting, May 17, 2007, Rochester, MN.
Conflict of interest: Varian Medical Systems Award.
ABSTRACT