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© 2001 American Society for Clinical Oncology Neurobehavioral Status and Health-Related Quality of Life in Newly Diagnosed High-Grade Glioma PatientsByFrom the Departments of Medical Psychology, Neurology, Neurosurgery, and Pulmonology, Vrije Universiteit Medical Center; Department of Neurosurgery, Academic Medical Center, University of Amsterdam; Departments of Neurology and Radiation Oncology, Division of Psychosocial Research & Epidemiology, the Netherlands Cancer Institute, Amsterdam; Departments of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands. Address reprint requests to M. Klein, PhD, Vrije Universiteit Medical Center, Department of Medical Psychology, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands; email: m.klein.psychol{at}med.vu.nl
PURPOSE: To evaluate the health-related quality of life (HRQOL) and cognitive functioning of high-grade glioma patients in the postneurosurgical period. PATIENTS AND METHODS: The HRQOL, as assessed by the Short-Form Health Survey-36, tumor-specific symptoms, and objective and subjective neuropsychologic functioning, of 68 newly diagnosed glioma patients were compared with that of 50 patients with non–small-cell lung cancer (NSCLC) and to age- and sex-matched healthy controls. The association between tumor lateralization, extent of resection, and use of medication, and the HRQOL outcomes was also investigated. RESULTS: The HRQOL of the two patient groups was similar but significantly lower than that of the healthy controls. Glioma patients reported significantly more neurologic symptoms and poorer objective and subjective neuropsychologic functioning than the NSCLC patients. Using healthy controls as the reference group, cognitive impairment assessed at the individual patient level was observed in all glioma patients and 52% of the NSCLC patients. Poor performance on timed tasks in the glioma group could be attributed, in large part, to visual and motor deficits. Tumor lateralization was found to affect neuropsychologic functioning in a predictable manner. The extent of resection was not related significantly to neuropsychologic functioning. Corticosteroid use was associated with better recognition memory, whereas antiepileptic drug use was correlated negatively with working memory capacity. CONCLUSION: The general HRQOL of glioma patients is similar to that of patients with NSCLC. However, they suffer from a number of condition-specific neurologic and neuropsychologic problems that have a significant impact on their daily lives in the postsurgical period, before treatment with radiotherapy.
HIGH-GRADE GLIOMAS are the most serious and aggressive types of malignant brain tumors, with median patient survival times ranging from less than 1 year to 3 years from initial diagnosis. Despite intensive treatment with surgery, radiotherapy, and chemotherapy, patients with these brain cancers invariably experience tumor recurrence, often within a year after completion of first-line therapy. Historically, evaluation of cancer therapies has focused on such biomedical outcomes as tumor response, disease-free and overall survival, and treatment-related toxicity. Although these outcome parameters remain central in the evaluation process, there is increasing recognition of the need to assess more formally and systematically the impact of cancer and its treatment on the functional, psychologic, and social health of the individual. Such health-related quality of life (HRQOL) factors have played a salient role in recent clinical studies in oncology, most notably among patients with local and advanced breast cancer and lung cancer. To date, little attention has been paid to the impact of a brain tumor on HRQOL and cognitive functioning.1 Patients with brain tumors not only have to cope with the diagnosis of cancer, but they are also often confronted with a diffuse decrease in cognitive functioning, as well as with more specific cognitive deficits related to tumor location.2,3 Patients with anaplastic astrocytomas and glioblastoma multiforme (GBM) typically present with symptoms of increased intracranial pressure, seizures, or focal neurologic deficits.4-7 Presenting symptoms, including alterations in personality and mood resulting from increased intracranial pressure, may be ameliorated by pharmacologic or neurosurgical interventions.8-11 Cognitive deficits in long-term surviving glioma patients have been attributed to treatment side effects, such as radiation encephalopathy or chemotherapy-induced neurotoxicity.3,12 Although cognitive deficits have been demonstrated in the postsurgical interval before the start of radiation therapy,13,14 these studies have not included adequate control groups. Cancer patients, regardless of their specific diagnosis, are confronted with a wide range of stressors throughout the illness and treatment trajectory. Therefore, estimates of HRQOL and cognitive function of patients with brain tumors should be based on comparisons with cancer patients with a similar prognosis but without CNS involvement. Only in this way can one determine whether the typical problems of people with cancer are exacerbated by the cognitive problems accompanying brain tumors.15 The primary objective of this study was to determine the HRQOL and neuropsychologic functioning of newly diagnosed, high-grade glioma patients who had undergone a biopsy or resection. To place the results pertaining to the glioma patients in perspective, comparisons were made with patients with non–small-cell lung cancer (NSCLC) and with normative data based on general population samples.
Patients and Control Subjects Between February 1997 and June 1999, consecutive, newly diagnosed and histologically confirmed high-grade glioma patients and newly diagnosed and histologically confirmed patients with locally advanced or metastatic NSCLC (stage IIIa/IIIb/IV), without clinical evidence of brain metastases were recruited into the study. Purposive sampling of NSCLC patients was carried out to match them as closely as possible in terms of age and sex to the glioma patient sample. Patients were recruited from the University Medical Center Utrecht (Utrecht), the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, the Vrije Universiteit Medical Center, the Slotervaart Hospital, the Academic Medical Center of the University of Amsterdam (Amsterdam), and the Sint Antonius Hospital (Nieuwegein), the Netherlands. Patients were excluded from the study who (1) had a life expectancy of less than 3 months; (2) were not eligible for radiotherapy (for glioma patients); and (3) did not have a basic proficiency in the Dutch language or who were unable to communicate. Eighteen of the 90 glioma patients who met the inclusion criteria declined to participate, and four patients had to be excluded after testing revealed severe aphasia, resulting in a final study sample of 68 patients. The rate of refusal among the NSCLC patients was higher, with 40 of the 90 patients who were approached declining participation. The major reason for nonparticipation for both glioma and NSCLC patients was the fact that the study would be emotionally too stressful or confronting or physically too tiresome. In addition to glioma and NSCLC patients, normative data of healthy controls were used as an additional anchor for interpreting the results. Healthy controls providing normative data for the neuropsychologic tests were drawn from a large, cross-sectional study of the biologic and psychologic determinants of cognitive aging, the Maastricht Aging Study.16 Two such normative samples were formed, those matched with high-grade glioma patients and those matched with NSCLC patients with respect to age, sex, and educational level. Educational level was assessed by a Dutch scoring system consisting of an eight-point scale, ranging from unfinished primary education (level 1) to university education (level 8).17 For purposes of comparing HRQOL outcomes, two age- and sex-matched samples were drawn from a large, nation-wide study whose aims were to translate, validate, and generate normative data on the Short-Form Health Survey (SF-36) Health Survey for use among Dutch-speaking residents of the Netherlands.18 Glioma and NSCLC patients were asked by their treating physician (ie, neurologist, neurosurgeon, radiation oncologist, or pulmonologist) to participate in the study. Informed consent procedures and testing in glioma patients were carried out in the postsurgical period, before the start of radiotherapy. NSCLC patients also completed the informed consent procedures and testing before the start of treatment (radiotherapy or chemotherapy). Before the day of formal neuropsychologic testing, patients completed a questionnaire concerning sociodemographic data, including age, sex, and educational level, self-perceived HRQOL, brain tumor-specific HRQOL issues, and self-reported cognitive functioning. An extensive battery of standardized neuropsychologic tests was administered during a session lasting between 60 and 90 minutes. The majority of both glioma patients and NSCLC patients were tested at home (73% and 88%, respectively). Assessment of patients’ performance status was carried out via a brief, standardized interview. Medical chart audits were performed to obtain data on tumor characteristics (histology and site), and treatment history (neurosurgery, use of corticosteroids, and antiepileptic drugs). Because volumetric data for most patients were not available, the neurosurgical intervention was classified as biopsy versus gross total or subtotal resection as evaluated by the neurosurgeon.
Study Measures Activities of daily living (ADL). The capacity to carry out ADL activities was assessed by means of the Barthel Activities of Daily Living Index.20,21 The Barthel index consists of 10 items assessing continence of bowels and bladder, grooming, toilet use, feeding, transfer, mobility, dressing, climbing stairs, and bathing. The items are ordered in ascending degree of difficulty. Higher scores indicate higher levels of functional independence. Neurologic functioning was rated by means of the Neurological Functional Status Scale developed by Order et al.22 Originally developed for use with patients with brain metastases, this scale has been used successfully in studies of brain tumor patients.23 Scores range from 1 to 4, with higher scores indicating better neurologic functioning. Self-reported cognitive functioning was assessed with a six-item scale developed for use in the Medical Outcomes Study (MOS).24 This scale assesses day-to-day problems in cognitive functioning of which the patient would be aware, including difficulty with reasoning and problem solving, slowed reaction time, forgetfulness, and problems with concentration. Raw scores are converted linearly to a 0 to 100 scale, with higher scores indicating higher levels of self-reported cognitive functioning. Health-related quality of life was assessed by means of the MOS SF-36.25 The SF-36 is a self-report questionnaire developed in the United States as part of a large, national study of the effect of various forms of health care delivery on patients’ health status and HRQOL.24 It is composed of 36 items, organized into eight multi-item scales assessing physical functioning, role limitations caused by physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations caused by emotional problems, and general mental health. Raw scores are converted linearly to 0 to 100 scales, with higher scores representing better levels of functioning. In addition to individual SF-36 scale scores, two higher-order component scores were calculated, a Physical Component Scale (PCS) and a Mental Component Scale (MCS).26 The SF-36 has been demonstrated to have excellent reliability and validity when used with healthy or patient populations in the United States27 and most European countries, including the Netherlands.18 Brain tumor-specific HRQOL issues were assessed by means of a questionnaire (Brain Cancer Module [BCM] 20) developed by Osoba et al.28 It contains five multi-item scales (future uncertainty, visual disorder, motor dysfunction, communication deficit, and emotional distress) and seven single items asking about headaches, seizures, drowsiness, hair loss, itching, weakness in the legs, and difficulties with bladder control. The four-item emotional distress scale was not included in the current analysis because of the substantial content overlap with the SF-36 mental health scale (MH). The BCM 20 raw scores are linearly converted to 0 to 100 scales, with higher scores representing lower levels of functioning. Neuropsychologic status. A battery of standard tests was used to assess neuropsychologic status. The total time required to complete the battery was approximately 60 minutes. Because of the heterogeneity in high-grade glioma patients of both origin and severity of cognitive disturbances,29 the cognitive test battery assessed a wide range of functions. Appendix 1 provides detailed information on this test battery. Because consideration of group means may obscure cognitive impairment evaluation at the level of the individual, an impairment score for each patient was calculated. This was performed by converting neuropsychologic test scores to z scores, using the mean scores of the NSCLC patients as a reference, and thus also weighing the psychologic impact of having cancer. Subsequently, a mean overall composite z score was computed. Neuropsychologic impairment was defined as a test score of two SDs below the mean of the NSCLC group. An overall impairment score was calculated for each individual patient by counting all tests that met this criterion. Because cognitive deficits also were expected in NSCLC patients, the fifth percentile of the NSCLC group was additionally used as a cutoff score for neuropsychologic impairment.30 Based on this latter cutoff score, both glioma and NSCLC patients were considered cognitively impaired if they had deviant scores on at least three tests. To obtain an estimate of the absolute percentage of cognitive deficits in glioma and NSCLC patients, the same algorithm was used with reference to their healthy control groups. Application of this algorithm indicated that glioma patients were defined as cognitively impaired if they had at least two deficient test scores and NSCLC patients if they had at least one deficient score.
Statistical Analysis Correlational and multiple stepwise regression analyses were performed to explore the association of the higher order SF-36 PCS and MCS scales with physical performance status (KPS), ADL-functioning (Barthel), and neurological status (Order). Additionally, the association between cognitive status and MCS scores was explored by additionally entering performance indices of the following four major cognitive domains in the regression model: (1) memory (total recall), (2) attention (Stroop Color-Word Test [SCWT]-III), (3) information processing capacity (Letter-Digit Substitution Test-writing), and (4) graphomotor speed (Concept Shifting Test [CST] motor). To examine the possibility that cognitive deficits in glioma patients in the postsurgical period might be related to any residual effects of general anesthesia, correlations between the time since neurosurgery and the indices of four major cognitive domains were calculated.
Sociodemographic and Clinical Characteristics Table 1 lists the sociodemographic and clinical characteristics of the high-grade glioma and NSCLC patients. Despite attempts at matching, the NSCLC patients were significantly older and had lower educational levels than the glioma patients (both P < .05). The majority of both glioma and NSCLC patients were male (78% and 76%, respectively). The age, sex, and educational levels of the healthy controls were comparable with those of the patient groups (Table 1). Levels of physical functioning as expressed by KPS scores did not differ significantly between glioma and NSCLC patients, although glioma patients were more limited in ADL (Barthel) and neurologic functioning (Order).
Glioma patients with tumors in the left hemisphere were not more limited in performance status (KPS) or in their capacity to carry out ADL activities (Barthel) than patients with right-sided tumors. However, lower scores on the Order scale measuring neurologic functioning characterized patients with tumors in the left hemisphere (P < .05). As far as the differential effects of biopsy versus gross total or subtotal resection were concerned, no differences could be demonstrated on performance status (KPS) or neurologic function (Order). The capacity to carry out ADL activities, however, was lower in patients who underwent biopsy as opposed to gross total or subtotal resection (P < .05). Karnofsky, Barthel, and Order scales were not associated significantly with the use of corticosteroids or antiepileptic drugs.
HRQOL
Results pertaining to the assessment of additional glioma-associated health problems (BCM 20) are listed in Table 2. Compared to NSCLC patients, glioma patients reported significantly more visual problems, motor dysfunction, communication deficits, headaches, and epileptic seizures than the NSCLC patients. No differential effects of cancer diagnosis were found on the perceived uncertainty concerning the future.
Lateralization of gliomas did not affect HRQOL as assessed by the SF-36 higher order PCS or MCS scores. Patients who had undergone biopsy had lower SF-36 PCS scores (P < .05) than patients who had gross total or subtotal resection. Patients using corticosteroids had lower PCS scores (P < .05) than those who did not, whereas the use of AEDs was not associated with lower PCS or MCS scores (data not shown in tabular form). Patients with tumors in the left hemisphere of the brain reported more problems with communication as evidenced by an elevated score on the relevant BCM 20 subscale (P < .01). No differences between surgery type could be demonstrated on any other brain tumor–specific issues (BCM 20). Patients who used corticosteroids at the time of testing did not report more BCM 20 symptoms, whereas patients who used AEDs reported significantly more communication deficits and uncertainty about the future (P < .01 and P < .05, respectively).
Neuropsychologic Performance
Compared with healthy controls, glioma patients did not evidence any increased difficulty with the primary recall of newly presented information (Visual Verbal Learning Test [VVLT] Trial 1). However, memory storage and learning capacity of glioma patients was limited. They benefited less from repeated presentation of the same material, thus leading to a smaller total amount of information stored in long-term memory (total recall and delta scores, respectively). When patients had to recall the information 20 minutes after the initial presentation, they had difficulty with both active and passive retrieval from long-term memory (delayed recall and delayed recognition, respectively). These findings indicate that glioma patients not only store less information in long-term memory, but also that they cannot easily retrieve this information at a later time. Performance on the working memory task was also indicative of a lower information processing capacity. In addition to being slower on attentional tasks with increasing task complexity (SCWT), glioma patients were more distracted by irrelevant information than healthy controls. Glioma patients also had difficulty with simple tasks, such as those requiring the generation of words from specific semantic categories (Fluency Test). Moreover, glioma patients seemed to have reductions in executive functions as evidenced by lower scores on tasks measuring visual scanning and conceptual tracking (CST). As one would expect, glioma patients with right-sided tumors had significantly lower scores than patients with left-sided tumors on tasks involving right-hemisphere function (line bisection; P < .05). These patients also had more problems with facial recognition (P < .05). Left-sided tumors were found to primarily affect measures of attentional and executive functioning, expressed by an increase in the time needed for visual scanning (CST A, P < .05), an increased susceptibility to interfering information (SCWT, P < .01), and a reduction in the generation of words from specific semantic categories (Fluency Test). Neither the nature of the neurosurgical intervention (biopsy or resection) nor the time elapsed since neurosurgery was associated significantly with neuropsychologic function. The use of corticosteroids was associated with better recognition memory (VVLT, P < .05), whereas patients using AEDs had a lower working memory capacity (working memory task, P < .05).
Using NSCLC patients as the reference group, 49% of the glioma group compared with 26% of the NSCLC group was found to be cognitively impaired ( As noted above, differences in visual and motor functioning could explain much of the observed difference in cognitive functioning between the glioma and NSCLC patients. An additional series of ANCOVAs, correcting for sociodemographics, was carried out to compare the cognitive functioning of glioma patients with or without visual and/or motor deficits. These analyses were restricted to those neuropsychologic tests that yielded nonsignificant between-group (glioma v NSCLC) differences after controlling for visual and motor problems. Glioma patients with lower self-reported visual functioning (47% of all patients) had significantly lower scores on four out of six timed tasks. Additionally, those patients with motor deficits (33%) had a general reduction in overall cognitive performance (MMSE) and showed more perseverative behavior (data not shown in tabular form).
Relationship Between Traditional Outcome Measures, HRQOL, and Cognitive Function Glioma patients’ deficits in attentional functioning, information processing capacity, and graphomotor speed correlated moderately with self-reported cognitive functioning (MOS; correlation = 0.46, P < .01; - 0.49, P < .01; and 0.33, P < .05, respectively). This indicates that glioma patients who have more objectively assessed neuropsychologic deficits tend to be more bothered by such cognitive problems in daily life. Both self-reported mental health (SF-36 subscale MH) and social functioning (SF-36 social functioning subscale) were associated significantly with self-reported cognitive functioning (MOS; correlations = -0.37, P < .01, and - 0.43, P < .01, respectively). Self-reported mental health (SF-36 subscale MH) was also associated significantly with information processing capacity (correlation = 0.33, P < .01). Deficits in other primary indexes of cognitive functioning were not significantly correlated with mental health scores.
This study evaluated the HRQOL and neuropsychologic functioning after neurosurgery in patients with newly diagnosed high-grade gliomas. The results indicate that the HRQOL of glioma patients is comparable with that of patients with NSCLC, except for social functioning, which is more negatively affected in glioma patients. Comparison of glioma and NSCLC patients with age- and sex-matched healthy controls revealed significantly lower scores in all HRQOL domains. The similarity in the self-reported HRQOL of glioma and NSCLC patients is not unexpected in that both patient groups have a poor prognosis, which is also reflected in their similar perceived uncertainty concerning the future. When using the NSCLC test score distributions as the reference, approximately half of the glioma patients and one quarter of the NSCLC patients were found to have impaired neuropsychologic functioning. Comparisons between glioma and NSCLC patients correcting for differences in neurologic functioning (BCM 20) suggest that cognitive differences between these patients groups are due, in large part, to impaired visual and motor functioning in glioma patients. Impaired self-reported visual functioning was found to be significantly associated with poorer performance on speeded tasks. Additionally, patients with self-reported limitations in motor functioning exhibited a reduction in overall cognitive performance, as well as increased perseverative behavior. These findings underscore the importance of assessing sensory and motor deficits as possible causative or aggravating factors when patients exhibit impaired cognitive functioning. Such information could be useful to patients, physicians, and other health care providers in determining the most appropriate strategies to help patients adjust to or compensate for their limitations in cognitive functioning. High-grade glioma patients are not only characterized by deficits in basic information-processing capacity but also by limitations in higher cognitive abilities, including attention and executive functions. It should be stressed that these results are based on comparisons with NSCLC patients who themselves exhibited signs of cognitive impairment. When using healthy controls as reference groups, all glioma patients and 52% of NSCLC patients were found to be cognitively impaired. Moreover, it should be noted that only 37% of the glioma patient sample had GBM, whereas this tumor accounts for the majority of all high-grade gliomas. This can largely be explained by the fact that patients for whom radiotherapy was not indicated or whose life expectancy was less than 3 months (both of which are more likely for patients with GBM) were not included in the sampling frame of the present study. Because patients with GBM typically present with more severe symptoms than those with other histologies, it is likely that the present findings underestimate the actual impact of glioma on HRQOL and, more specifically, on cognitive functioning. There are several possible explanations for the cognitive deficits found in glioma patients tested after neurosurgery. The first and most likely is the effect of the tumor itself. Apart from relief of cognitive dysfunctioning caused by increased intracranial pressure, surgery is not likely to improve cognitive functioning. Cognitive deficits might also be a result of the neurosurgical intervention. If the surgical intervention was to have detrimental effects on cognitive functioning, one would expect major surgery to have more impact than a biopsy. However, we did not observe any significant differences between patients who underwent biopsy versus gross total or subtotal resection. Because neuropsychologic data were not available preceding the surgical intervention, no firm conclusions can be drawn. The time elapsed since neurosurgery was found to be unrelated to neuropsychologic functioning. It is thus unlikely that cognitive deficits in glioma patients in the postsurgical period were caused by any residual effects of general anesthesia. Another possible explanation of cognitive dysfunctioning is the use of medication in the postoperative period, such as corticosteroids or AEDs. Corticosteroids are associated with a large number of physical side effects,31 and only recently have their detrimental effects on frontal lobe and memory functions been acknowledged.32,33 AEDs can give increase to decreased cognitive functioning, depression, and irritability,34 although several of the newer AEDs demonstrate few adverse cognitive effects.35 In our study, we found no evidence of a general deleterious effect of corticosteroids on cognitive function. In fact, we found a slightly better memory performance in glioma patients using corticosteroids compared with patients who were not. In contrast, we found patients using AEDs to have a lower working memory capacity. Whether this difference is a result of medication taken and/or to the underlying epilepsy remains to be elucidated. Psychologic effects (eg, anxiety, depression, or fatigue) might also influence negatively cognitive functioning.36 In the current study, we found a significant association between scores on the SF-36 mental health summary score and several cognitive domains. This might also explain some of the cognitive disturbances noted among the NSCLC patients. Unfortunately, indices of mental health were not available from the healthy control group providing neuropsychologic test data. Therefore, we could not discern whether compromised mental health in glioma patients might be a major factor contributing to their lower level of cognitive functioning. With regard to the NSCLC patients, Stuschke et al37 found NSCLC survivors treated with systemic chemotherapy and chest irradiation to have cognitive disturbances that could not be attributed to brain metastases or prophylactic cranial irradiation. In the current study, we found cognitive disturbances to be present even before radiochemotherapy of the lung. This was also observed in the study by Komaki et al,38 who attributed pretreatment cognitive deficits in small-cell lung cancer to paraneoplastic limbic encephalopathy. Cognitive impairment after prophylactic cranial irradiation in NSCLC patients has been hypothesized to be instigated by immunologic dysfunction, treatment effects, opportunistic infection, depression, or microscopic CNS metastasis.38 Future studies are needed to investigate these issues further. Self-reported cognitive functioning (MOS) of high-grade glioma patients correlated significantly with objective measures of cognitive function, suggesting that these patients are able to monitor their cognitive capacity relatively well. This contrasts with the study of Taphoorn et al39 in a population of patients with low-grade gliomas and the study of van Dam et al30 among patients with high-risk breast cancer receiving high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, both of which found low correlations between subjective and objective measures of cognitive function. Although glioma patients had lower MMSE scores than NSCLC patients, it should be stressed that the MMSE cannot be used as a substitute for an extensive neuropsychologic test battery. The MMSE aims primarily at evaluating a general cognitive decline in dementing patients, and is not sensitive enough to detect subtle tumor- or treatment-related changes.40 However, in longitudinal studies where the level of functioning of some patients with high-grade glioma is expected to be too low to permit standard neuropsychologic assessment, the MMSE can be administered to ensure comparability of test sessions. The study results have important implications for the optimal management of patients with high-grade gliomas. Systematic assessment of cognitive function and quality of life needs to be incorporated into clinical trials to determine how different treatment regimens affect these parameters, especially because current treatments are likely to have a limited effect on the length of survival. An important rationale for selecting a noncurative therapy may be related to its profile of neurologic side effects and impact on quality of life. It should be stressed, however, that the correlation between self-reported quality of life and objective measures of physical, neurologic, and cognitive functioning may change during the course of the disease. Patients may experience reductions in their neurologic or cognitive abilities because of tumor growth or treatment side effects. This does not necessarily imply that their quality of life will change in a similar way. Patients, for instance, might consider themselves fortunate because they survived surgery or because they were able to undergo radiotherapy, even in the face of serious cognitive limitations. Thus, neuropsychologic tests are a useful tool in evaluating specific tumor or treatment effects, whereas quality-of-life estimates are indispensable for the evaluation of the subjective experience of brain cancer and its treatment on the daily life of the patient.
Supported by grant no. VU96-1155 from the Dutch Cancer Society. We thank H. Baaijen, P. Baas, E.B. Bongartz, J.H. Borger, D. González González, M.C.C.M. Hulshof, J.A. Langendijk, I. van der Lee, W.F. Luitjes, T.J. Postma, P.E. Postmus, J.G. Salverda, N. Schlösser, F.M.N.H. Schramel, S.I. Tjahja, and J.G. Wolbers for their permission to recruit their patients, Astrid Albersen, Judith Grit, Nick Guldemond, and Walter Oomen for their invaluable help in tracing and testing patients, Martin Muller for statistical assistance, and Jaap Lindeboom for his advice on neuropsychologic assessment.
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2, P < .05). Glioma patients not only had more objectively confirmable cognitive deficits; they were also characterized by lower levels of self-reported cognitive functioning (MOS, P < .001). Using healthy controls as reference groups, all glioma patients and 52% of the NSCLC patients were found to be cognitively impaired. The nature of the neurosurgical intervention, the lateralization of the tumor, or the use of corticosteroids did not affect MOS scores. However, patients who used AEDs were characterized by lower levels of self-reported cognitive functioning (MOS, P < .01). 
