Cancer patients often complain of ``chemobrain,'' or woolly-headedness during treatment. While they are typically reassured this will go away, little attempt has been made until now to see if these subtle problems linger years later. The new study, conducted at Dartmouth Medical School, found that people who get standard chemotherapy appear to be about twice as likely as other cancer patients to score poorly on various intelligence tests an average of 10 years after their treatment. Doctors say the findings suggest that aggressive treatment with chemotherapy may be unwise in some people with early-stage cancer unless the drugs can substantially improve chances of survival. Tim A. Ahles, a psychologist, presented the results Tuesday at a meeting in Tampa of the American Cancer Society. He said that while his is one of the first formal studies of the problem, the results are unlikely to surprise many cancer patients.

Ahles said that when he spoke recently about the findings at a meeting of cancer survivors, he worried his discouraging news would upset the audience. Instead, they seemed relieved that scientists were finally taking seriously a complaint they had made for years. He said that many years after treatment, some cancer survivors say they still have trouble remembering and concentrating. Some say they need a calculator for math problems they once could have solved in their heads. Others have to read a page twice to absorb what's being said.

``In talking to someone, you'd never notice this,'' Ahles said. ``But it is very relevant to them.''

Ahles noted that lots of things during chemotherapy can make people feel unfocused. Often they are anemic, sick from the chemotherapy and sleepy from anti-nausea medicines. But intellectual ability gradually comes back as they recover. ``The question is whether it returns to pretreatment levels,'' he said. ``The inference from our data is that for a subgroup of patients, it does not.''

In his study, Ahles tested 71 patients who were cancer-free after getting chemotherapy an average of 10 years earlier for breast cancer or lymphoma. They were compared with 58 who had been treated with radiation or surgery alone.

Overall, the chemotherapy patients scored significantly worse, though most were still thinking clearly.

However, between one-quarter and one-third of those who got chemotherapy scored near the bottom in at least four of the nine areas of intellectual ability that the researchers measured. Only half as many of the patients who got surgery or radiation alone did this badly.

Dr. William Wood of Emory University in Atlanta noted that patients with early-stage cancer often opt for aggressive chemotherapy, even though statistically it offers only a percentage point or two improvement in survival.

``This is may give second thoughts to people who really would not get much benefit'' from chemotherapy, Wood said. Earlier studies have found a chance of lingering intellectual problems in people who receive high-dose chemotherapy, such as those undergoing bone marrow transplants. Doctors treating children with leukemia have also successfully turned to less toxic doses after finding the drugs cause learning problems.

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Cancer Invest 2001;19(8):812-20

Cognitive effects of standard-dose chemotherapy in patients with cancer.

Ahles TA, Saykin A.

Department of Psychiatry and Center for Psycho-Oncology Research, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.

Adult cancer survivors have reported experiencing persistent changes in cognitive function following treatment with chemotherapy. Increasing evidence supports the hypothesis that standard-dose chemotherapy can produce cognitive deficits in a subgroup of adult cancer survivors. Although these cognitive changes tend to be subtle deficits in memory, concentration, and the ability to remain focused or organized, these alterations in cognitive ability can have a significant impact on patients' quality of life generally, and on meeting career and educational goals specifically. This manuscript reviews the literature relevant to the cognitive impact of standard-dose chemotherapy in adults, outlines methodological issues related to the study of cognitive functioning in people with cancer, and discusses future directions for research in this area.

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J Clin Oncol 2002 Jan 15;20(2):485-93

Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma.

Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, Whedon MB, Bivens S, Mitchell T, Greenberg ER, Silberfarb PM.

Department of Psychiatry and Center for Psycho-Oncology Research, New Hampshire Hospital, Concord, NH, USA. Tim.A.Ahles@dartmouth.edu

PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only.

PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory).

RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P <.04), particularly in the domains of verbal memory (P <.01) and psychomotor functioning (P <.03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P <.01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P <.02).

CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy

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