Science + Technology

UCLA Imaging Study Shows Changes in Brain Function Even 10 Years After Cancer Patients Undergo Chemotherapy

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Cancer survivors, take note. The mental fog andforgetfulness of "chemo brain" are no figment of your imagination.

A new UCLA study shows that chemotherapy causes changes tothe brain's metabolism and blood flow that can linger at least 10 years aftertreatment. Reported Oct. 5 in the online edition of the journal BreastCancer Research and Treatment, the findings may help to explain the disruptedthought processes and confusion that plague many chemotherapy patients.

"People with 'chemo brain' oftencan't focus, remember things or multitask the way they did beforechemotherapy," explained Dr. Daniel Silverman, head of neuronuclearimaging and associate professor of molecular and medical pharmacology at theDavid Geffen School of Medicine at UCLA. "Our study demonstrates for thefirst time that patients suffering from these cognitive symptoms have specificalterations in brain metabolism."

Silverman and his colleagues used positron emissiontomography (PET) to scan the brains of 21 women who had undergone surgery toremove breast tumors five to 10 years earlier. Sixteen of them had beentreated with chemotherapy regimens near the time of their surgeries to reducethe risk of cancer recurrence. 

The team compared PET images evaluating the chemotherapy patients'brain function to PET scans from five breast-cancer patients who underwentsurgery only, and 13 control subjects who did not have breast cancer orchemotherapy. 

As the women performed a series ofshort-term memory exercises, the UCLA team measured blood flow to theirbrains.  The researchers also ran a scan of the patients' resting brainmetabolism after the women finished the exercises.

"The PET scans show a link betweenchemo-brain symptoms and lower metabolism in a key region of the frontalcortex," explained Silverman. "We found that the lower thepatient's resting brain metabolism rate was, the more difficulty she hadperforming the memory test."

 The scans revealed thatblood flow to the frontal cortex and cerebellum spiked as the chemotherapypatients performed the memory tests, indicating a rapid jump in these brainregions' activity level.

"The same area of the frontal lobe that showed lower restingmetabolism displayed a substantialleap in activity when the patients were performing the memory exercise," saidSilverman. "In effect, these women's brains were working harder than thecontrol subjects' to recall the same information."

Finally, the researchers discovered that women who underwenthormonal therapy in addition to chemotherapy displayed changes to their basalganglia, a part of the brain that works to bridge thought and action. Onaverage, these women showed an 8 percent drop in resting metabolism in thisbrain region.

"Chemotherapy used to be prescribed primarily to treat metastatic disease," observed Silverman. "Now it'scommon for doctors to administer chemotherapy to patients near the time ofsurgery to prevent metastasis. As many of these patients become long-termsurvivors, doctors are recognizing lasting side-effects of chemotherapy, and,in particular, the kind of chemo-brain symptoms we are studying."

"Our findings suggest that PET scans could be used tomonitor the effects of chemotherapy on brain metabolism," he added. "Theapproach could be easily added to current whole-body PET or PET/CT scansalready being used to monitor patients for tumor response to therapy."

Although chemo brain is an acknowledged phenomenon, doctorsdon't know what mechanisms cause it. More studies are needed to uncover how thedamage occurs and whether modification of chemotherapy drugs could prevent it.

The National Cancer Institute recently awarded a five-yeargrant to oncologist Dr. Patricia Ganz, who isorganizing a long-term study on chemo brain of a larger group of breast-cancersurvivors with Silverman and their colleagues at UCLA.

More than 211,000 new cases of breast cancer are diagnosed ayear, making it the most common cancer in women. Experts estimate that atleast 25 percent of chemotherapy patients are affected by chemo brain, and arecent study by the University of Minnesota reported an82 percent rate.  

The Breast Cancer Research Foundation and American CancerSociety supported the study. Silverman's UCLA coauthors included ChristineDy, Jasmine Lai, Betty Pio,Michael Phelps and Steven Castellon, as well as Laura Abraham, Kari Waddell,Laura Petersen and Dr. Patricia Ganz of the Jonsson Comprehensive Cancer Center. Castellon isalso affiliated with the Greater Los Angeles Veterans Affairs HealthcareSystem.

-UCLA-

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