Dose-Dependent Effects of Radiation Therapy on Cerebral Blood Flow, Metabolism and Neurocognitive Dysfunction

Reviewer: Voika BarAd, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 18, 2005

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Presenter: C.A. Hahn
Presenter's Affiliation: Radiation Oncology, Duke University Medical Center, Durham, NC
Type of Session: Scientific

Background

Radiation therapy can cause neurocognitive dysfunction in patients treated for brain tumors.  Frequent reported side effects include subtle neurocognitive dysfunction, short term memory impairment, global neuropsychological deficit.  There is significant interest in finding ways to decrease the rates of these difficult toxicities that impact on the patients quality of life.  The study prospectively assessed changes in neuropsychological function in a series of patients irradiated for brain tumors and related these to changes in functional PET brain imaging.

Materials and Methods

  • 11 subjects were enrolled, mean age 48 (21-69), 5 females, 6 males.
  • The histology was Anaplastic astrocytoma in 4 patients, Meningeoma in 2, Anaplastic Oligodendroglioma in 2, and a subject each with: Pituitary adenoma, Astrocytoma and undifferentiated histology.
  • Mean educational level was 13 years.
  • All patients received 3D conformal CT planned cranial irradiation for CNS tumors.
  • Baseline pre-radiotherapy evaluation included PET scanning with both 18F-FDG (metabolism) and 15O-H2O (blood flow) and neuropsychological testing.
  • The same evaluation was repeated 3 weeks and 6 months post treatment.
  • Baseline and follow up PET data were registered with treatment planning CT scans and hence the radiotherapy dose distribution.
  • Quantitative image analyses related changes in regional 18F-FDG PET and 15O-H2O PET in relation to regional radiotherapy dose.
  • Regions of brain were combined in 5 Gy dose bins from 5 to 60 Gy.
  • The pre and post- radiotherapy scans regions receiving < 5 Gy served as controls for image normalization.
  • Analyses were performed in order to ascertain correlations between changes in 18F-FDG PET, 15O-H2O PET, regional radiation dose, follow up time and neuropsychological test scores.
  • 7 patients completed 3 week and 6 patients 6 months follow up imaging studies. 6 patients completed follow up neuropsychological testing.

Results

  • PET data revealed reduction in FDG uptake with averages in dose bins of 2-6% in the regions of the brain receiving > 40 Gy at 3 weeks and 6 months follow up.
  • 15O-H2O PET revealed increases (< 10%) at 3 weeks in relative regional blood flow in brain receiving > 30 Gy, but much less at 6 months follow up series.
  • There were significant correlations between decease in FDG uptake in irradiated brain and increased scores from Sympton Checklist-90-R with average increase in T-score of 2. These changes were most evident at 6 months follow up.
  • Wisconsin Card Sorting Test, a measure of problem solving and cognitive flexibility, demonstrated significant correlation of decreased FDG uptake with increased errors in test performance and increased perseveration, average decline in T-score of 11.

Author's Conclusions

  • Dose-dependent response of CNS tissue can be detected using PET.
  • These quantifiable decreases in CNS function have significant correlation with decreased performance on neuropsychological test scores for problem solving, cognitive flexibility and global measures of psychopathology.

Clinical/Scientific Implications

The study assessed the functional changes in normal brain tissue by PET, and correlated them with the neurocognitive and neuropsychological dysfunction.  Longer follow up is needed in order to ascertain the late neurocognitive and neuropsychological side effects of radiotherapy.  A better quantification of the dose dependant effects of radiotherapy and its impact on the neuropsychological function may provide a rational basis for radiotherapy treatment planning for CNS tumors in order to minimize adverse effects of treatment and optimize patient quality of life. Further evaluation of functional imaging in this setting is warranted.


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