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© 2002 American Society for Clinical Oncology Neuropsychologic Impact of Standard-Dose Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and LymphomaByFrom the Department of Psychiatry and Center for Psycho-Oncology Research, Department of Psychiatry (Neuropsychology Program), Community and Family Medicine, and Norris Cotton Cancer Center, New Hampshire Hospital, Concord, NH. Address reprint requests to Tim A. Ahles, PhD, Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756; email: Tim.A.Ahles{at}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.
COGNITIVE DEFICITS associated with cancer treatment can have a dramatic effect on patients’ quality of life1 and have been recognized as a problem by the President’s Cancer Panel2 and as a challenge facing cancer survivors by the National Coalition for Cancer Survivorship.3 Although early research focused on the cognitive effects of treatment on children with cancer, recent reviews of the adult literature4,5 have shown that a growing body of research has supported the hypothesis that adults with cancer experience cognitive deficits associated with a variety of treatments, including cranial radiation, conventional chemotherapy, high-dose chemotherapy and hematopoietic transplantation, and biologic response modifiers. Improved understanding of the impact of systemic chemotherapy on cognitive functioning is critical for the following reasons: (1) increasing numbers of people with cancer are becoming concerned about this issue2,3; (2) cognitive problems can have a major impact on survivors’ educational and career decisions and general quality of life; (3) patients need to be aware of potential cognitive effects of treatment to make informed treatment decisions; (4) similar research with children resulted in modifications of treatment regimens that reduced the negative cognitive effects while maintaining treatment efficacy6; and (5) cognitive rehabilitation approaches, which have been shown to significantly improve functioning of other types of patients with subtle cognitive deficits,7,8 may be effective for cancer patients experiencing cognitive deficits secondary to chemotherapy. Increasing attention has focused on the measurement of cognitive effects of standard-dose chemotherapy using standardized neuropsychologic testing. Two studies9,10 found that a high percentage of patients with lung and breast cancer treated with systemic chemotherapy (95% and 75%, respectively) experienced lower scores than published norms in memory and concentration. In each study, patients were evaluated within 6 months of treatment; therefore, the impairment may have been attributable to the ongoing, acute effects of chemotherapy. Other studies have compared cancer patients treated with systemic chemotherapy with a matched sample of cancer patients who receive local therapy only. van Dam et al11 evaluated patients with breast cancer an average of 2 years after treatment who were randomized to high-dose chemotherapy plus tamoxifen or standard-dose therapy (fluorouracil, epidoxorubicin, and cyclophosphamide) plus tamoxifen. They also included a control group of stage I patients who were treated with local therapy only (surgery plus local radiotherapy). Patients in the high-dose arm were more likely to demonstrate cognitive impairment (32%); however, a greater number of patients in the standard-dose arm (17%) demonstrated cognitive impairment compared with the local therapy group (9%). Schagen et al12 studied 39 patients with breast cancer treated with cyclophosphamide, methotrexate, and fluorouracil (CMF) plus or minus tamoxifen and a control group of 34 age-matched patients with axillary node–negative breast cancer who received surgery and local radiotherapy but no systemic chemotherapy. Neuropsychologic testing occurred approximately 2 years after treatment. Their results demonstrated that patients treated with CMF compared with those who received local therapy only had significantly more problems with concentration (31% v 6%) and memory (21% v 3%). Across all domains, cognitive impairment was seen in 28% of chemotherapy patients and 12% of controls. Finally, Brezden et al13 compared cognitive functioning in women with breast cancer who were presently receiving adjuvant chemotherapy (CMF or cyclophosphamide, epirubicin, and fluorouracil) or were more than 1 year past chemotherapy (median, 25 months) with that of healthy controls. Consistent with the studies described above, a greater number of patients in both treatment groups had moderate or severe cognitive impairment compared with healthy controls as measured by the High Sensitivity Cognitive Screen. Taken together, these studies support the hypothesis that cognitive deficits, particularly in the areas of memory and concentration, are associated with cancer chemotherapy regimens during treatment, in the short-term after treatment, and up to 2 years after treatment. Additionally, qualitative studies have suggested that these cognitive problems may persist for many years after treatment.3,14 Therefore, the purpose of the present study was to investigate the neuropsychologic impact of chemotherapy regimens in long-term (> 5 years past diagnosis) survivors of breast cancer and lymphoma.
Cancer survivors treated with systemic chemotherapy (breast cancer, n = 35; lymphoma, n = 36) or local therapy (breast cancer, n = 35; lymphoma, n = 22) were identified through the Norris Cotton Cancer Center Tumor Registry. The patients with lymphoma were nearly equally divided between Hodgkin’s (n = 31) and non-Hodgkin’s (n = 27) lymphoma. Systemic chemotherapy was defined as standard-dose chemotherapy, whereas local therapy was defined as surgery or radiation therapy, excluding CNS radiation. Additionally, survivors had to have been a minimum of 5 years after diagnosis, receiving no cancer treatment except tamoxifen, disease-free, greater than 18 years of age when diagnosed, and fluent in and able to read English. Survivors were excluded if they had CNS disease, treatment with CNS radiation or intrathecal therapy, neurobehavioral risk factors, including head injury with loss of consciousness, history of neurologic disorder, a learning disability, or an axis I psychiatric disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), specifically, substance abuse, mood, anxiety-based, or psychotic-spectrum disorders. All participating survivors provided signed, informed consent.
Survivors who initially agreed to participate received a call from a research nurse who described the purpose and procedures of the study and conducted a brief, standardized medical and neurobehavioral screening designed to assess general medical and psychiatric status, with a particular focus on neurobehavioral risk factors, signs and symptoms of CNS disorder, and medications that could potentially alter neuropsychologic functioning. Survivors who were eligible after the medical screening and remained willing to participate were scheduled for a time to sign informed consent forms and complete the assessment battery (approximately 2 hours in duration). The comparison group of cancer survivors who had received local therapy were frequency matched by diagnosis and age with distributions of the chemotherapy cases. Testing occurred in the neuropsychology testing offices of the Department of Psychiatry (77%) or in survivors’ homes (23%, 19 chemotherapy and 10 local therapy survivors). Two hundred six cancer survivors were initially approached and 28 (14%) were ineligible on the basis of the exclusion criteria described above. Of the remaining 178 eligible survivors, 45 (25%) declined to participate, primarily because they were too busy, and 133 (75%) agreed to participate. Of the survivors who agreed to participate, 128 (94.5%) completed testing, one (0.5%) was unable to complete testing, and four (2%) agreed to participate but were never able to schedule a time for testing. The assessment battery included standardized neuropsychologic tests and measures of affective variables and fatigue, which may impact performance on neuropsychologic tests. The neuropsychologic tests (grouped by cognitive domain below) have established utility in clinical neuropsychologic assessment and published normative data15 and were selected from a larger set recommended by a panel of experts.16 Neuropsychologic tests were grouped into domains to reduce the number of statistical comparisons based on previous factor analyses in larger data sets and consensus of experienced neuropsychologists.16
Neuropsychologic Assessment Battery
Self-Report Measures of Cognitive and Psychologic Function The Center for Epidemiological Study–Depression (CES-D)29 is a 20-item measure of depressive symptoms that has been widely used in epidemiologic studies of depression. Patients are asked to rate how frequently they have experienced each symptom on a 4-point scale ranging from "rarely or none of the time" to "most or all of the time." The CES-D has been widely studied and has strong data supporting its validity and reliability.30 The Spielberger State-Trait Anxiety Inventory (STAI)31 contains two 20-item forms that measure state anxiety (the level of present anxiety) and trait anxiety (the general level of anxiety experienced). Extensive data on reliability and validity support the utility of the test.31 The Fatigue Symptom Inventory (FSI)32 is a 14-item measure designed to assess the intensity, frequency, and disruptiveness of fatigue experienced by cancer patients. Patients rate each item on an 11-point scale ranging from 0 (not a problem) to 10 (an extreme problem). Evidence supports the validity and reliability of the instrument in a cancer population.32 Using the demographic data form, we assessed basic demographic data (age, sex, and education level) as well as treatment and disease-related characteristics (ie, type of cancer therapy and time since cancer diagnosis). Medical records were abstracted to determine cancer treatment history (ie, type and dosages of chemotherapy agents, surgical procedures, and type and dosage of radiation) and treatment for other medical disorders.
Statistical Analysis Multivariate analysis of covariance (MANCOVA) followed by analysis of covariance (ANCOVA) was used to evaluate treatment and diagnosis factors in terms of the domain scores. ANCOVA was used for comparisons of the Squire Memory Self-Rating Questionnaire. Logistic regression analysis was used to compare rates of low performance based on the Neuropsychological Performance Index. Pearson’s correlations and analysis of variance were used to identify and evaluate potential confounders of treatment and performance on neuropsychologic testing.
Table 1 presents the basic demographic characteristics, Table 2 presents the stage of disease at diagnosis, and Table 3 lists the chemotherapy regimens administered by diagnosis. The majority of breast cancer patients had stage 0, I, or II disease, whereas the lymphoma patients had a wider distribution across disease stage. Review of Table 3 reveals that patients primarily received standard treatments for their disease. Importantly, most patients (85%) received only one type of chemotherapy regimen. The median number of cycles of chemotherapy within a regimen was six (range, one to 17). A significant (P < .02) but low correlation (r = -.31) was found between the number of cycles and the mean of the neuropsychologic domain scores, indicating that more cycles of chemotherapy was associated with lower neuropsychological performance. Finally, of the breast cancer survivors, 18 had taken tamoxifen at some time (13 chemotherapy and five local therapy survivors). However, only four survivors were taking tamoxifen at the time of testing (three chemotherapy survivors and one local therapy survivor). Analysis of the group of survivors who had ever taken tamoxifen compared with those who had never taken tamoxifen revealed no significant differences on any of the neuropsychologic domain scores.
Frequency matching of breast cancer cases on age was successful, given the numbers of survivors available; however, because of substantially smaller numbers of lymphoma survivors, frequency matching still resulted in a mean age difference of 7.3 years between the chemotherapy and local therapy groups. When comparing the chemotherapy and local groups for potential confounders, the only significant difference that emerged was a longer time since treatment in the local therapy group (P < .03), attributable mostly to longer time since treatment among the lymphoma survivors. However, correlation analysis revealed no significant associations between time since treatment and performance on neuropsychologic testing. Chemotherapy and local therapy groups did not differ on level of depression, state and trait anxiety, and fatigue (Table 4). Comparison of the mean CES-D and STAI scores with published norms indicated that these scores fell well within normal limits for both the chemotherapy and local therapy groups. Furthermore, Pearson’s correlations were calculated between the domain scores and age, education, depression (CES-D), state and trait anxiety (STAI), and fatigue (FSI). Significant negative correlations with neuropsychologic performance emerged for present age and positive correlations emerged with years of education, but no other variables were significant. Therefore, only age and education were used as covariates in the subsequent analyses.
Impact of Treatment Domain scores. Table 5 displays the unadjusted, non–z-transformed scores by treatment status and diagnosis for each of the neuropsychologic tests that were used to calculate the domain scores. MANCOVA was conducted with treatment (chemotherapy v local therapy) and diagnosis (breast v lymphoma) as independent variables, the nine domain scores as dependent variables, and age and education as covariates. The overall MANCOVA demonstrated a significant effect for treatment (P < .04) but not for diagnosis (P < .15). Univariate analyses revealed significant treatment differences in the domains of verbal memory (P < .01) and psychomotor functioning (P < .03). There was also a nonsignificant trend for group differences in spatial ability (P < .10) and visual memory (P < .12). For each outcome above, survivors who had received systemic chemotherapy scored lower than survivors who had received local therapy only. Examination of the individual tests within the domains where there was a significant treatment difference revealed that survivors treated with chemotherapy scored significantly lower on logical memory I (P < .03) and II (P < .01) from the verbal memory domain and digit symbol (P < .02) from the psychomotor domain. Figure 1 graphically displays the adjusted, z-transformed domain scores for the systemic chemotherapy versus local therapy groups, and Table 6 displays the adjusted, mean z-transformed domain scores and SDs. Finally, to evaluate whether the results are significantly influenced by a few outliers, Fig 2 displays the distribution of the global neuropsychologic performance score (the mean of the domain scores) by treatment. As can be seen, the data are normally distributed and support the hypothesis that survivors treated with chemotherapy, as a group, scored significantly lower than survivors treated with local therapy.
Neuropsychological Performance Index. The Neuropsychological Performance Index was used to construct 2 x 2 frequency tables for neuropsychologic performance (lower quartile v upper three quartiles) by treatment (chemotherapy v local therapy). Logistic regression, which included treatment, diagnosis, age, and education, in the model revealed a significant treatment effect (P < .01), with a higher percentage of survivors who had received systemic chemotherapy scoring in the low performance range (39%) compared with survivors receiving local therapy (14%). To evaluate the adequacy of the definition of low performance as scores in the lower quartile in four or more domains, we also categorized survivors using three domains in the lower quartile (chemotherapy, 50%; local therapy, 23%; P < .01) and five domains in the lower quartile (chemotherapy, 24%; local therapy, 5%; P < .01). Regardless of the cutpoint used, significantly more survivors in the chemotherapy group scored in the low performance range (always greater than double) compared with the local therapy group. Similar 2 x 2 frequency tables constructed with the Neuropsychological Performance Index and diagnosis revealed no significant differences between the breast cancer and lymphoma survivors. Self-perceived changes in memory functioning. The 18-item Squire Memory Self-Rating Scale item data were divided into three cluster scales on the basis of factor analysis of the present survivor study data set and a large database of epilepsy patients with known memory dysfunction.36 The factor structure was nearly identical in both groups. Scales were composed of items with high loadings on only one of three factors. Three of 18 items were not included because of ambiguous loadings. Factor I included items mainly related to learning new information; factor II assessed working memory and attention and concentration; factor III included items about retrieval from remote memory (ie, from "long ago" or childhood). All items were rated by participants on a scale from -4 (worse than ever before) to +4 (better than ever before). Unit-weighted averages of items in each cluster were computed, preserving this scaling. Results were analyzed with treatment (chemotherapy v local therapy) as a single between-group factor, memory cluster as the within-subject factor, and age and education as covariates (Fig 3). Factor II (working memory) was rated significantly lower by the chemotherapy group (P < .02); factor I (new learning) showed a similar tendency (P < .07); and factor III (remote retrieval) did not differ between the groups. However, correlations between the Squire subscales and the neuropsychologic domain scores were low and nonsignificant.
The primary purpose of this study was to compare the cognitive functioning of long-term survivors of breast cancer or lymphoma who were treated with systemic chemotherapy or local therapy only. The multivariate analysis of the mean domain scores and analysis of the Neuropsychological Performance Index strongly support the hypothesis that deficits in cognitive functioning are associated with systemic chemotherapy. The multivariate analysis demonstrated a global difference between the chemotherapy and local therapy groups, and univariate analyses revealed significant differences in the domains of verbal memory and psychomotor functioning. Both of these functional domains have high sensitivity to cerebral dysfunction associated with multiple etiologies. The significant overall effect of treatment across domains, as shown by Fig 1, suggests that the effect is relatively diffuse, as might be expected given the mixture of systemic treatment regimens. The cognitive deficits seen in this study were identified in survivors, on average, approximately 10 years after chemotherapy. Therefore, it seems that the cognitive deficits seen shortly after treatment9,10 and approximately 2 years after treatment11-13 can persist long after treatment and perhaps indefinitely. In understanding this pattern of results, it is also noteworthy that the vast majority of patients in the chemotherapy group (85%) received only one standard-dose chemotherapy regimen. Therefore, the population studied is similar to the survivors studied by the investigators from the Netherlands and Canada in terms of the amount of chemotherapy received. Importantly, the differences in cognitive functioning persisted after controlling for the potential confounders of age and education level. Other potential factors (depression, anxiety, and fatigue) were evaluated and not found to be confounders in this study. This is likely because of the fact that survivors with major psychosocial problems (including depression and anxiety) were screened out, and the survivors who participated were 5 years or more past treatment and disease-free. Consequently, most were functioning at a high level and scored within the normal range for these psychologic measures. The Neuropsychological Performance Index analysis at multiple thresholds indicated that between 24% and 50% of survivors treated with systemic chemotherapy scored in the low performance range compared with 5% to 23% of patients treated with local therapy. Stated another way, at each performance cutoff score, greater than double the number of survivors treated with chemotherapy scored in the impaired range compared with the local therapy group. Putting these data into context, low performance is defined in terms of the performance of the overall group of survivors. However, compared with published norms (Table 5), performance was generally within the normal range. This supports the observation that the effects of chemotherapy, although important to the individual, are relatively subtle. Overall, results from the analysis of the Neuropsychological Performance Index are similar to those presented by investigators from the Netherlands11,12 and Canada13 and suggest that only a subgroup of patients may experience cognitive deficits after chemotherapy. Survivors treated with chemotherapy also self-rated greater change in memory function as measured by the Squire Memory Scale compared with survivors treated with local therapy. However, correlations between the Squire scores and the neuropsychologic domain scores were low and nonsignificant. This pattern has been observed in epilepsy,28 mild head injury,37 and human immunodeficiency virus infection27,38 and may be related to factors that influence self-report measures more dramatically than performance on neuropsychologic measures (eg, self-perceptions like "I have a bad memory" or recent memory difficulties related to fatigue or mood). On the other hand, self-report measures like the Squire may not be sensitive enough to reliably assess the relatively subtle memory changes associated with chemotherapy; therefore, other, more appropriate measures may need to be identified or developed. A limitation of this study is the lack of pretreatment assessment of cognitive functioning. This type of analysis does not capture decline in patients who may have scored above normal before treatment and then scored in the normal range after treatment. The design of the present study also does not allow one to identify people who may have scored below the norm on certain neuropsychologic tests before treatment who were essentially unaffected by the chemotherapy.39-41 Furthermore, this approach does not allow analysis of potential interactive effects with normal aging processes. Clearly, a critical next step in this area is the use of prospective, longitudinal designs in which patients are evaluated before treatment and followed over time after treatment. A longitudinal study should also help to shed light on potential mechanisms by which chemotherapy causes decrements in performance on neuropsychologic tests. If the cognitive impact of chemotherapy is attributable to a direct impact on the brain, it is reasonable to predict that there are certain cytotoxic agents or combinations of agents that are more likely to be associated with cognitive decline than others. On the other hand, if the cognitive deficits are caused by a physiologic reaction that is stimulated by a wide variety of chemotherapy agents (eg, an immunologic response), then cognitive changes may be more closely associated with a certain side-effects profile. A longitudinal study will allow for a more precise examination of the association between the chemotherapy regimens (eg, agents and doses) and side-effect profiles and cognitive functioning. Finally, because we were studying long-term cancer survivors, a formal assessment of the effects of menopause was not included. Although women may experience cognitive problems after menopause,39 this is not likely to be a major confound in the present study for the following reasons: most of the women were over 50 years of age, ie, likely postmenopausal (58 in the chemotherapy group and 43 in the local therapy group) at the time of testing; differences in cognitive functioning between the chemotherapy and local therapy groups were seen even though age was included as a covariate in the analysis; and our data suggest that the effect of chemotherapy is relatively global, whereas research with postmenopausal women suggests that the cognitive deficits experienced are relatively specific to verbal memory.42 Nevertheless, this is an important issue that would best be studied with a longitudinal design in which menopausal status (both naturally occurring and chemotherapy-induced) could be evaluated over time and correlated with cognitive performance. In conclusion, data from the present study support the hypothesis that systemic chemotherapy can be associated with cognitive deficits, at least in a subpopulation of patients. The cognitive deficits found tended to be fairly subtle (ie, most survivors scored within the normal range compared with published norms); therefore, the survival benefits of chemotherapy far outweigh the potential risks to cognitive functioning for most patients. On the other hand, given the growing concerns among patients about cognitive problems associated with chemotherapy, patients need accurate information regarding potential long-term effects of chemotherapy (of which cognitive problems are only one) to add to the risk/benefit equation as they make treatment decisions. Before cognitive side effects of chemotherapy can reasonably be integrated into the informed decision-making process, significantly more research is required to understand which chemotherapeutic agents are responsible for causing the cognitive problems, the mechanism by which systemic chemotherapy creates cognitive deficits, and which variables predict who will experience long-term cognitive problems. Future studies are also needed to evaluate whether interventions can be developed to prevent the occurrence of cognitive impairment or to rehabilitate survivors who continue to experience cognitive problems.
Supported by a supplement to Norris Cotton Cancer Center Core grant P30CA23108 from the Office of Cancer Survivors, National Cancer Institute, Bethesda, MD.
1. Ahles TA, Saykin A: Cognitive effects of standard-dose chemotherapy in patients with cancer. Cancer Invest 19: 812–820, 2002 2. President’s Cancer Panel: Cancer Care Issues in the United States: Quality of Care, Quality of Life. Washington DC, National Cancer Program, National Cancer Institute, 1999 3. Ferrell BR, Hassey Dow K: Quality of life among long-term cancer survivors. Oncology 11: 565–576, 1997[Medline] 4. Walch SE, Ahles TA, Saykin AJ: Neuropsychological impact of cancer and cancer treatments in adults, in Holland J (ed): Textbook for Psycho-Oncology. New York NY, Oxford University Press, 1998, pp 940–945 5. Meyers CA: Neurocognitive dysfunction in cancer patients. Oncology 14: 75–79, 2000[Medline] 6. Walch SE, Ahles TA, Saykin AJ: Cognitive sequelae of treatment in children, in Holland J (ed): Textbook for Psycho-Oncology. New York NY, Oxford University Press, 1998, pp 500–505 7. Cimprich B: Development of an intervention to restore attention in cancer patients. Cancer Nurs 16: 83–92, 1993[Medline] 8. Sohlberg MM, Mateer CA: Introduction to Cognitive Rehabilitation. New York NY, Guilford Press, 1989 9. Komaki R, Meyers CA, Shin DM, et al: Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 33: 179–182, 1995[CrossRef][Medline] 10. Wieneke MH, Dienst ER: Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psycho-Oncology 4: 61–66, 1995
11.
van Dam FSAM, Schagen SB, Muller MJ, et al: Impairment of cognitive function in women receiving adjuvant treatment for high risk breast cancer: High dose versus standard dose chemotherapy. J Natl Cancer Inst 90: 210–218, 1998 12. Schagen SB, van Dam FSAM, Muller MJ, et al: Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 85: 640–650, 1999[CrossRef][Medline]
13.
Brezden CB, Philips KA, Abdolell M, et al: Cognitive junction in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 18: 2695–2701, 2000 14. Whedon MB, Stearns D, Mills L: Quality of life of long-term adult survivors of autologous bone marrow transplantation. Oncol Nurs Forum 22: 1527–1537, 1995[Medline] 15. Saykin AJ, Gur RC, Gur RE, et al: Normative neuropsychological test performance: Effects of age, education, gender and ethnicity. Appl Neuropsychol 2: 79–88, 1995[CrossRef][Medline] 16. Gur RC, Saykin A, Benton A, et al: Behavioral imaging, III: Inter-rater agreement and reliability of weightings. Neuropsychiatr Neuropsychol Behav Neurol 3: 113–124, 1990 17. Wechsler D: Wechsler Adult Intelligence Scale, ed 3 (WAIS-III). San Antonio TX, Harcourt Brace & Co, 1997 18. Wilkinson GS: The Wide Range Achievement Test, Revised (WRAT-3). Wilmington DE, Wide Range, 1993 19. Kaplan EF, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia PA, Lea & Febiger, 1978 20. Benton AL, Hamsher K: Multilingual Aphasia Examination. Iowa City IA, University of Iowa, 1978 21. Delis DC, Kramer JH, Kaplan E, et al: California Verbal Learning Test. Cleveland OH, Psychological Corporation, 1983 22. Wechsler D: Wechsler Memory Scale-Revised (WMS-R). New York NY, Psychological Corporation, 1987 23. Reitan RM: Trail Making Test: Manual for Administration and Scoring. Tucson AZ, Reitan Neuropsychological Laboratory, 1971 24. Reitan RM: Manual for Administration of Neuropsychological Test Batteries for Adults and Children. Tucson AZ, Reitan Neuropsychological Laboratory, 1979 25. Gordon M: The Gordon Diagnostic System. New York NY, Gordon Systems Inc, 1986 26. Squire LR, Wetzel CD, Slater PC: Memory complaint after electroconvulsive therapy: Assessment with a new self-rating instrument. Biol Psychiatry 14: 791–801, 1979[Medline] 27. Saykin AJ, Janssen R, Sprehn G, et al: Longitudinal evaluation of neuropsychological function in homosexual men with HIV-1 infection: 18 month follow-up. Neuropsychiat Clin Neurosci 3: 286–298, 1991 28. Deutsch GK, Saykin AJ, Sperling MR: Metamemory in temporal lobe epilepsy assessment. 3: 255–263, 1996 29. Radloff LS: The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1: 385–392, 1977[CrossRef] 30. Plutchick R, Conte HR: Self-report scales for the measurement of depression. Psychiatr Ann 19: 367–371, 1989 31. Spielberger CD, Gorsuch RL, Lushene RG: Manual for the State-Trait Anxiety Inventory. Palo Alto CA, Consulting Press, 1971 32. Hann DM, Jacobsen PB, Martin SC, et al: Fatigue in women treated with bone marrow transplantation for breast cancer: A comparison with women with no history of cancer. Support Care Cancer 5: 44–52, 1997[CrossRef][Medline] 33. Paolo AM, Troster AI, Ryan JJ: California Verbal Learning Test: Normative data for the elderly. J Clin Exper Neuropsychol 19: 220–234, 1997 34. Ivnik RJ, Malec JF, Tangalos RJ, et al: Mayo’s older Americans normative studies: WMS-R norms for ages 50-94. Clin Neuropsychol 6: 49–82, 1992 (suppl) 35. Spreen O, Strauss E: A Compendium of Neuropsychological Tests. New York NY, Oxford University Press, 1998 36. Saykin AJ, Robinson LJ, Stafiniak P, et al: Neuropsychological effects of temporal lobectomy: Acute changes in memory, language, and music, in Bennett T (ed): Neuropsychology of Epilepsy. New York NY, Plenum Press, 1992, pp 263–290 37. McAllister TW, Flashman LA, Sparling MB, et al: Relationship of psychopathology to post-concussive symptoms one month after mild traumatic brain injury (MTBI). J Neuropsychiatry Clin Neurosci 11: 150–151, 1999 38. Saykin AJ, Janssen RS, Cannon L, et al: Neurobehavioral patterns in HIV-1 infection: Relation of cognitive and affective changes and activities of daily living. J Clin Exp Neuropsychol 12: 1, 1990 (abstr)[Medline] 39. Ahles TA, Silberfarb PM, Herndon JH, et al: Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: A study by the cancer and leukemia group B. J Clin Oncol 16: 1954–1960, 1998[Abstract] 40. Phipps S, Dunavant M, Srivastava DK, et al: Neuropsychological outcome in survivors of pediatric bone marrow transplantation. Paper presented at Cancer Survivorship: Research Challenges and Opportunities for the New Millennium, Bethesda, MD, March 8–9, 1999 41. Syrjala KL, Dikmen S, Roth-Roener S, et al: Prospective longitudinal neuropsychological testing of patients receiving high dose chemotherapy: Results and methodological issues. Paper presented at Cancer Survivorship: Research Challenges and Opportunities for the New Millennium, Bethesda MD, March 8–9, 1999 42. Sherwin BB: Estrogen and cognitive functioning in women. Proc Soc Exp Biol Med 217: 17–22, 1998[CrossRef][Medline] Submitted August 2, 2002; accepted August 29, 2002.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 analysis revealed that the difference in frequency of testing at home between the chemotherapy and local therapy groups was not significant. The neuropsychologic examiners were bachelor degree–prepared technicians who were trained and supervised by the Director of Neuropsychology, a board-certified neuropsychologist (A.J.S.). The neuropsychology examiners were blind to survivors’ treatment history. The conduct of this study was approved by the institutional review board of Dartmouth Medical School. 
