Standard-Dose Chemo May Have Long-Term Cognitive Effects

NEW YORK—Preliminary findings from a study of long-term cancer survivors suggest a linkage of cognitive deficits to standard-dose chemotherapy, Timothy Ahles, PhD, reported at the Pan American Congress of Psychosocial and Behavioral Oncology.

Dr. Ahles, professor of psychiatry, Dartmouth-Hitchcock Medical Center, said that data already analyzed show differences in cognitive functioning between groups who received standard-dose chemotherapy and those treated only with local therapy such as surgery or targeted radiation.

His study is enrolling patients who were treated at Dartmouth-Hitchcock for breast cancer or lymphoma at least 5 years ago. Some patients are 20 years post-treatment, he said, and all are cancer-free.

The preliminary data are based on 57 breast cancer patients, 27 who received chemotherapy and 30 who had local therapy, and 53 lymphoma patients, 35 treated with chemotherapy and 18 with local measures. Average education in all the groups is more than 2 years of college.

“We excluded anyone who had any evidence of CNS disease; previous treatment with any kind of CNS radiation or intrathecal therapy; any history of head injury, neurologic disorder, or substance abuse; and any axis I psychiatric disorders,” Dr. Ahles said. “We also measured depression, anxiety, social support, and fatigue because we were concerned that all of these elements can affect cognitive function, and we wanted to be able to control for these kinds of effects.”

From results on a variety of neuro-psychologic tests, Dr. Ahles and his colleagues created composite domain scores. The domains include verbal ability, learning, and memory, as well as visual memory, block design, psychomotor and motor functioning, and attention.

Plotting of the composite domains after correction for such variables as age and education revealed differences between the chemotherapy patients and those receiving local therapy only. Deviations from the mean were “fairly consistently” above the line for the local therapy group, Dr. Ahles said, and below it for the chemotherapy cohort.

“Differences were statistically significant,” he said, “for block design, verbal learning, and psychomotor functioning.” Multivariate analysis also showed an overall effect, he said, adding that the only domain that did not differ between groups was attention.

Another analysis focused on patients who scored in the lowest quartile on specific tests. Those who scored this low in four or more tests were considered to be in an impaired range, Dr. Ahles said. Again, a difference emerged, with 35% of chemotherapy patients falling into this range, compared with 15% of those who had received local therapy.

The researchers also looked at lowest quartile cutoffs of 3 and 5 domains to define impairment. “It doesn’t matter where you draw the line,” Dr. Ahles said. “The difference between the treatment groups is maintained.”

Patients’ Perceptions

Dr. Ahles has also attempted to find out whether these long-term survivors perceive that they are having cognitive problems. Using the Squire Memory Test, a self-report measure of function, he found the biggest difference in perceived decrement over time in working memory. “There’s a borderline significance in new learning,” he said. “Survivors or patients undergoing therapy often tell you they feel like they can’t learn new material as well as they used to.”

Eventually, Dr. Ahles hopes that interventions will be developed to help patients cope with cognitive changes linked to chemotherapy. Meanwhile, he points to the need to define who is likely to be affected. “If it is accurate that only a subset of patients is affected,” he asked, “what accounts for that subset? Medications? A history of head injury or learning disabilities? Are there other biologic or genetic factors that predispose people to be affected adversely by chemotherapy?”