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Changes in Brain Function Persist 10 Years after Chemotherapy, Imaging Study Suggests

doi: 10.1097/01.COT.0000290046.96639.b8
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Chemotherapy can cause changes to the brain's metabolism and blood flow that can linger for up to 10 years after treatment, according to a study in the October 5 online edition of Breast Cancer Research and Treatment.

“People with ‘chemo brain’ often can't focus, remember things, or multitask the way they did before chemotherapy,” lead author Daniel H. S. Silverman, MD, PhD, Head of the Neuronuclear Imaging Section of the Ahmanson Biological Imaging Division at UCLA Medical Center, said in a news release.

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“Our study demonstrates for the first time that patients suffering from these cognitive symptoms have specific alternations in brain metabolism.”

The study included 16 right-handed women who had histories of breast cancer and were treated with adjuvant chemotherapy. All had undergone their last course of cytotoxic chemotherapy five to 10 years prior to enrollment in this study.

Eleven patients had also undergone tamoxifen therapy, and a control group of eight right-handed women had never received chemotherapy. The control group members were well-matched to the chemotherapy-treated patients in time elapsed since diagnosis, as well as in age at enrollment and age at diagnosis.

The chemotherapy group was studied with the Rey-Osterrieth Complex Figure (ROCF) Delayed Recall test and positron emission tomography (PET). PET scans with [O-15] water were acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism.

PET scans revealed that modulation of cerebral blood flow in specific regions of the frontal cortex and cerebellum was significantly altered in chemotherapy-treated patients.

The most significant difference between the chemotherapy group and the control group was located in the inferior frontal gyrus. Peak activation occurring in the inferior frontal gyrus corresponded to a 2.3% increase of activity during recall and was highly significant in chemotherapy-treated patients, while activity in this area was only weakly increased in untreated patients.

Untreated patients demonstrated greatest cortical activation in the parietal cortex. Chemotherapy-treated patients experienced significant activations in the contralateral posterior cerebellum near the midline, as well as the superior frontal gyrus.

Patients in the chemotherapy group scored an average of 3.2 points lower than untreated patients did on the ROCF Delayed Recall test. There were no significant differences in resting metabolism between the control and adjuvant therapy groups.

In examining drug-class specific effects, metabolism of the basal ganglia was about 7% to 8% lower in patients receiving cytotoxic chemotherapy plus tamoxifen compared with patients receiving cytotoxic chemotherapy only. Chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated patients.

“Our findings suggest that PET scans could be used to monitor the effects of chemotherapy on brain metabolism,” Dr. Silverman said. “The approach could be easily added to current whole-body PET or PET/CT scans already being used to monitor patients for tumor response to therapy.”

© 2006 Lippincott Williams & Wilkins, Inc.
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