MRI Scans Show Brain Structure Changes After Chemotherapy

Zosia Chustecka

November 27, 2006

November 27, 2006 — Breast cancer patients receiving adjuvant chemotherapy often complain of cognitive impairment after the treatment, symptoms that have been termed "chemobrain." Now a study using magnetic resonance imaging (MRI) has found brain changes in such patients, suggesting a potential effect of adjuvant chemotherapy on brain structure, say the researchers. The findings come from a Japanese study in Cancer, published online November 27, 2006.

The changes were seen at 1 year after chemotherapy but were not visible after 3 years. This "can lead us to speculate that the brain volume change related to adjuvant chemotherapy may well recover over the course of time," the researchers comment.

The study was headed by Masatoshi Inagaki, MD, PhD, from the National Cancer Center Hospital East, in Chiba, and relied on databases containing brain MRI scans of breast cancer survivors. The team compared scans from patients who had been exposed to chemotherapy (including tegafur-uracil [UFT], cyclophosphamide, methotrexate, and 5-fluorouracil) with those who had not been exposed and looked at scans taken within 1 year of surgery and more than 3 years after surgery.

The 1-year study showed that patients exposed to chemotherapy (n = 51) had smaller regional volumes of both gray and white matter than patients who had not been exposed (n = 55). The brain regions affected included the prefrontal cortex, parahippocampal gyrus, and precuneus, and the volumes of these 3 regions were significantly correlated with indices of attention/concentration and/or visual memory, the researchers comment.

The 3-year study showed no significant differences in regional brain volumes between those exposed to chemotherapy (n = 73) and those not exposed (n = 59). The mean time from completion of adjuvant chemotherapy to this MRI scan was 4.2 years. "Regional brain structural changes and cognitive impairments observed in cancer survivors exposed to adjuvant chemotherapy may recover in time," the researchers comment.

The group also looked at MRI brain scans in healthy volunteers, who were recruited via a local newspaper. These showed no significant differences in regional brain volumes when compared with the scans from breast cancer survivors who had not been exposed to chemotherapy, suggesting that the cancer itself had no effect on the brain.

"These results lead to the idea that adjuvant chemotherapy could have a temporary effect on brain structure, which would recover 3 years after the cancer surgery," Dr. Inagaki told Medscape. Although the researchers measured memory function, it was not the end point of the study, and further studies are needed to explain chemobrain, he added. A detailed, longitudinal controlled study with a large sample is needed.

Approached for comment by Medscape, Gordon Winocur, PhD, from the Rotman Research Institute, in Toronto, Ontario, said; "The study by Inagaki et al is very important in that utilizes high-resolution MRI to show that chemotherapy produces significant structural changes in the brain that could account for the loss of memory and related cognitive function that is frequently reported by cancer patients undergoing such treatment.

"The results provide further evidence that these cognitive changes, commonly termed 'chemobrain,' can be related to changes in brain function independently of the effects of stress associated with the disease and treatment," he continued.

"Importantly, the authors related changes in specific cognitive processes to corresponding changes in localized brain regions. Of particular interest is that the authors report reductions in volume in hippocampus and prefrontal cortex, 2 brain regions that have been implicated by previous research in the cognitive deficits associated with chemotherapy," including studies from his own group.

The finding that brain changes were noted after 1 year, but not at 3 years, is interesting in that it suggests that they may not be permanent, Dr. Winocur commented.  However, that is in conflict with other results that the authors cite, as well as long-term complaints of cancer patients.  Further research into the long-term effects of chemotherapeutic drugs on cognition is clearly warranted, he concluded.

Cancer. Published online November 27, 2007.

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