• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • 1
    CommentGo Back
Download
 
162
News
|
JNCI
Vol. 100, Issue 3
|
February 6, 2008
 NEWS
Chemobrain Is Real but May Need New Name
By Karyn Hede
C
ancer patients know that chemo-brain is real. The nearly ubiquitousexperience of foggy thinkingimmediately after chemotherapy treat-ment has even inspired T-shirts and but-tons emblazoned with “My Name isChemo Brain.” For some cancer survi- vors, the cognitive effects of chemother-apy such as lack of concentration andshort-term memory loss linger for yearsafter treatment, but little is known about who is most likely to suffer a long-termdeficit or how to guard against it.Confounding factors such as fatigue anddepression—as well as widely divergentpatient experiences—have made studyingthe cognitive consequences of chemo-therapy problematic. That obstacle hasled to a disconnectbetween patientexperiences and phy-sician attention tothe issue.“I think it’s prob-ably true that there’sstill a fair amount of skepticism amongst some people abouthow real of a phenomenon this is,” says Tim Ahles, Ph.D., a cognitive psycholo-gist at Memorial Sloan-Kettering CancerCenter in New York. “Even thoughpatients have been talking about this for years, really since the 1970s, it’s only thelast 10 years that anyone has been doingsystematic research.”Now a series of studies that combineneuropsychological testing with sophisti-cated brain imaging and molecular analyseshas allowed investigators to get a handle on what had previously been seen as an inde-scribable phenomenon. And severalresearch studies focusing on treatment arebeginning to yield new strategies to miti-gate some of the quality-of-life issues thataccompany short-term memory loss afterchemotherapy.In the first study of its kind, DanielSilverman, M.D., Ph.D., associate profes-sor of molecular and medical pharmacol-ogy at UCLA’s David Geffen School of  Medicine, and his colleagues conductedpositron emission tomography imagingstudies of 16 long-term breast cancer survi- vors with persistent memory problems,eight former breast cancer patients whohad never had chemotherapy, and 10healthy control subjects. The researchers, who were blinded, administered a delayed-recall memory test while observing brainmetabolic activity. The studies demonstrated that the women who had received chemotherapy had a lower resting brain metabolism, andthe questions activated a larger portion of their frontal cortex than that in untreated women. “The more impaired they were inperforming the mem-ory task, the lowerthe resting metabo-lism was in that areaof the brain,”Silverman said. “Thatsame part of thebrain, the inferiorfrontal cortex, is less metabolically active tobegin with, so … to perform the same cog-nitive task, [the subjects have] to work thatpart of the brain that much harder to get upto the level that they would have if they hadnot been impaired.”Complementary functional magneticresonance imaging studies have yieldedsimilar results. Andrew Saykin, Psy.D.,director of Indiana University’s center forneuroimaging, and his colleagues arestudying breast cancer patients beforeand after chemotherapy, breast cancerpatients who did not receive chemother-apy, and healthy control subjects.Preliminary results, presented at theannual meeting of the Organization forHuman Brain Mapping in June 2007,show a disrupted pattern of brain activa-tion 1 month after chemotherapy, withless overall activity in bilateral prefrontalregions. Saykin said that the group willrepeat the imaging 1 year after the womenfinish chemotherapy before publishingthe dataset.
Should It Be “Cancer Brain”?
However, other studies suggest thatblaming cognitive problems solely onchemotherapy is too limiting. Ahles andhis colleagues recently published a neu-ropsychological study of 132 newly diag-nosed breast cancer patients and 45healthy control subjects that concludedpatients with stage I–III invasive diseasehad statistically significantly lower cogni-tive performance before treatment thanthat of patients with noninvasive diseaseor no disease, althoughboth sets of patientsscored within what isconsidered the “nor-mal” reference range. Ahles suggests thatother factors associ-ated with invasive can-cer, such as elevatedlevels of proinflamma-tory cytokines or DNA damage, may contribute to poorer baseline cognitiveperformance.Previous studies have established thedeleterious effects of cytokines on cogni-tive function. Janette Vardy, M.D., Ph.D.,a medical oncologist at the University of Sydney in Australia, is collaborating withIan Tannock, M.D., Ph.D., of Princess Margaret Hospital in Toronto, on a study of cytokine levels and functional magneticresonance imaging results in 120 breastcancer patients. The goal is to associatecytokine levels with levels of fatigue andcognitive impairment. Preliminary datasuggest that cytokine levels are elevated inall cancer patients compared with those incontrol subjects, but with the current sam-ple size no conclusions can be drawn, Vardy said.Other factors may also be involved thatpoint to issues besides chemotherapy.
Robert Ferguson, Ph.D.
“If you treat the brain as amental muscle and exerciseit, these functions will improve.” 
 
 jnci.oxfordjournals.org
JNCI
|
News
163
NEWS
“One of the first things we ought to do isrename ‘chemobrain,’” Ahles said. “… Formost women with breast cancer, they alsoreceive hormonal intervention like tamoxi-fen or aromatase inhibitors. There areissues like age, stress, anxiety, [and] depres-sion that can factor in. If anything, it hasbecome more complicated than werealized.”
Organizing the Field
 The recent convergence of data suggest-ing a biological basis for chemobrain hassparked an international effort to standard-ize research methods and to prioritizefuture research directions. The InternationalCognition and Cancer Task Force, formedduring the October 2006 international cog-nitive workshop in Venice, Italy, is creatinga Web site that will serve both physiciansand patients seeking assistance with man-aging cognitive symptoms associated withcancer treatment, according to Vardy,cochair of the group.“There are groups of us around the world that are trying to study this prob-lem,” Ahles said. “One of the things wefound when we get together is that every-body is using different sets of tests, differ-ent inclusion and exclusion criteria fortheir studies, and different statistical analy-sis plans. We are trying to come up with acore of common measures so that we canbe comparing across studies.”Indeed, the methodological problems with early studies on cognitive impairmentin cancer patients are well known (
 see
JNatl Cancer Inst 2003;95:190–7). Also,most studies on cognitive changes havebeen small and have included few olderpatients, even though most cancer patientsand cancer survivors are elderly, Ahlessaid. According to a 2007 Institute of  Medicine report on cancer in the elderly,60% of all cancer survivors are older than65 years. Andrea Bial, M.D., a geriatrician at theUniversity of Chicago, published a reviewin
Critical Reviews in Oncology/Hematology
 in which she pointed out that only 17% of studies on cognition included cancerpatients whose mean age was more than65 years. “There is an obvious and unmet
Survey Points to Doctor–PatientMiscommunication in Chemobrain Research
Defining what it means to have chemobrain is difficult, but getting a handle on the prevalenceand effect of cognitive changes resulting from systemic chemotherapy treatment has been evenharder to pin down. Estimates of how many cancer patients are affected range from 14% to85%. Patient advocacy groups say that no matter how many are affected, it’s time to focus onchemobrain as a major quality-of-life issue for survivors.“I’m hearing from a lot of patients that their doctors don’t believe them or they don’t thinkit’s important,” said Janet Colantuono, executive director of Hurricane Voices Breast CancerFoundation. “They think it’s age- or hormone-related, anything other than being an impact fromthe cancer treatment. So we identified this gap between the patient and the physician, and wewanted to do something that would help close that gap.”Working with Ian Tannock, M.D., Ph.D., of Princess Margaret Hospital in Toronto and JanetteVardy, M.D., Ph.D., of the University of Sydney, the advocacy group conducted the first surveyto gather information from cancer survivors about their experience with chemotherapy-relatedcognitive changes. A self-selected group of 471 men and women diagnosed with any type ofcancer participated. Colantuono said that the survey was not meant to be scientific but rather togive an overall picture of what experiences patients had and how it affected their ability to func-tion in daily life. Highlights of the survey included the following:
 
•
Most respondents indicated an effect on their functioning and relationships at home (62%)and in employment outside the home (62%). The effects rangeed from taking longer to doordinary jobs around the house to having to change careers or stop working.
•
Of the 102 respondents 5 or more years out from treatment, 92% were still affected bycognitive changes
—
 61% at the same level they first experienced after treatment. Only 8%reported that their symptoms had gone away.
•
Most patients reported that medical professionals do not help them cope with cognitivechanges. Sixty-three percent of patients conferred with their doctors, but only 10% felt thatthey were provided information and support to manage their symptoms.As the number of survivors continues to grow, cognitive deficits will become a critical qual-ity-of-life concern for millions of cancer patients, the report concludes. Colantuono said the sur-vey results indicate that cancer care teams need to better incorporate cognitive changes into thearray of side effects discussed and monitored throughout treatment and afterward.
—Karyn Hede
need to look specifically at cognitive issuesin older folks,” Bial said. “It is a compli-cated issue because being elderly is anindependent risk factor for cognitiveimpairment. It is important that futurestudies include a sufficient number of elderly patients in their trials so thatoncologists have enough information toadvise elderly patients about potentialdeleterious effects of chemotherapy oncognition.”
Lessening the Effects
 While researchers are working to identify  who is most at risk for long-term cogni-tive problems, others are turning theirattention to mitigating its effects. Onerecent approach involves giving a mildstimulant to patients who have justcompleted chemotherapy. At the 2007 American Society for Clinical Oncology meeting, Sadhna Kohli, Ph.D., a profes-sor at the University of Rochester, pre-sented data showing that modafinil, amedication approved for sleep apnea,improved short-term memory in breastcancer patients. In the study, 68 women who complained of memory problems 2 years after breast cancer chemotherapy  were given modafinil for 4 weeks. For thenext 4 weeks, half the women continuedto receive the drug, while the others weregiven a placebo. Women who receivedmodafinil showed modest but statistically significant improvement in cognitive
continued on page 169 
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
modafan

Buy Provigil Online @ ProvigilBuy.com. No prescription is required. Stay awake up to 90 Hours. Worldwide shipping. Cheapest price ever! Check http://www.provigilbuy.com

reply02 / 01 / 2010
You must be to leave a comment.
Submit
Characters: ...