Chad M. Gundy

PURPOSE: Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. PATIENTS AND METHODS: This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. RESULTS: The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. CONCLUSION: Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting.

PURPOSE: Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas. PATIENTS AND METHODS: One hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health-related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up. RESULTS: At the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months. CONCLUSION: The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.

PURPOSE: To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer (BC). PATIENTS AND METHODS: Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch postmenopausal patients with BC, who did not receive chemotherapy. Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC. RESULTS: Participants included 80 tamoxifen users (mean age, 68.7 years; range 51 to 84), 99 exemestane users (mean age, 68.3 years; range, 50 to 82), and 120 healthy controls (mean age, 66.2 years; range, 49 to 86). At T2, after adjustment for T1 performance, exemestane users did not perform statistically significantly worse than healthy controls on any cognitive domain. In contrast, tamoxifen users performed statistically significantly worse than healthy controls on verbal memory (P < .01; Cohen's d = .43) and executive functioning (P = .01; Cohen's d = .40), and statistically significantly worse than exemestane users on information processing speed (P = .02; Cohen's d = .36). With respect to visual memory, working memory, verbal fluency, reaction speed, and motor speed, no significant differences between the three groups were found. CONCLUSION: After 1 year of adjuvant therapy, tamoxifen use is associated with statistically significant lower functioning in verbal memory and executive functioning, whereas exemestane use is not associated with statistically significant lower cognitive functioning in postmenopausal patients with BC. Our results accentuate the need to include assessments of cognitive effects of adjuvant endocrine treatment in long-term safety studies.

PURPOSE: To investigate the generic and condition-specific health-related quality of life (HRQL) of patients with low-grade glioma (LGG). PATIENTS AND METHODS: A total of 195 patients with LGG, which was diagnosed, on average, 5.6 years before the study, were compared with 100 patients with hematologic (non-Hodgkin's) lymphoma and chronic lymphatic leukemia cancer (NHL/CLL) and 205 general population controls who were comparable with patients with LGG at the group level for age, sex, and education (healthy controls). Generic HRQL was assessed with the Short Form-36 (SF-36) Health Survey, and condition-specific HRQL was assessed with the Medical Outcomes Study cognitive function questionnaire and the European Organisation for Research and Treatment of Cancer brain cancer module. Objective neurocognitive functioning was assessed with a standardized battery of neuropsychological tests. RESULTS: No statistically significant differences were observed between patients with LGG and patients with NHL/CLL in SF-36 scores. Patients with LGG scored significantly lower than healthy controls on six of eight scales and on the mental health component score of the SF-36. Approximately one quarter of patients with LGG reported serious neurocognitive symptoms. Female sex, epilepsy burden, and number of objectively assessed neurocognitive deficits were associated significantly with both generic and condition-specific HRQL. Clinical variables, including the time since diagnosis, tumor lateralization, extent of surgery, and radiotherapy, did not show a consistent relationship with HRQL. CONCLUSION: Patients with LGG experienced significant problems across a broad range of HRQL domains, many of which were not condition-specific. However, the neurocognitive deficits and epilepsy that were relatively prevalent among patients with LGG were associated with negative HRQL outcomes and, thus, contributed additionally to the vulnerability of this population of patients with cancer.