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Standard-Dose Chemo May Have Long-Term Cognitive Effects

Jun 1, 2000
Volume: 
9
Issue: 
6

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?”

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