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Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors a
G. C. Wochos , C. H. Semerjian a
ac
ab
& K. S. Walsh
Children’sNational Medical Center, Washington, DC 20010, USA
b
The George Washington University Medical Center, Washington, DC 20052, USA c
Roosevelt University, Chicago, IL 60605, USA Published online: 24 Oct 2014.
Click for updates To cite this article: G. C. Wochos, C. H. Semerjian & K. S. Walsh (2014) Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors, The Clinical Neuropsychologist, 28:8, 1243-1257, DOI: 10.1080/13854046.2014.971875 To link to this article: http://dx.doi.org/10.1080/13854046.2014.971875
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The Clinical Neuropsychologist, 2014 Vol. 28, No. 8, 1243–1257, http://dx.doi.org/10.1080/13854046.2014.971875
Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors G. C. Wochos1, C. H. Semerjian1,3, and K. S. Walsh1,2 1
Children’sNational Medical Center, Washington, DC 20010, USA The George Washington University Medical Center, Washington, DC 20052, USA 3 Roosevelt University, Chicago, IL 60605, USA
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2
We aimed to compare executive function (EF) outcomes in pediatric brain tumor (BT) survivors compared with healthy children (HC) across multiple settings. This retrospective cross-sectional study of BT survivors and age- and gender-matched HC analyzed scale patterns of parent and teacher ratings of EF (Behavior Ratings of Executive Function; BRIEF). We also analyzed relationships between groups and raters (parent/teacher) and clinical elevations across EF domains on the BRIEF. Group differences in aspects of EF emerged from parent ratings in working memory (WM), while significant interactions from teacher ratings emerged on nearly all EF scales. Parents reported impaired cognitive/behavioral flexibility in the BT group four times more than parents of HC. Teachers rated survivors significantly more poorly as a group on the majority of EF domains, and indicated clinical impairment in cognitive/behavioral flexibility, emotional regulation, self-starting/initiation, WM, and planning and organization (P/O) four to ten times more often than the teachers of HC. Overall, teacher ratings of EF impairment in pediatric BT survivors were significantly greater than parent ratings, who reported far fewer EF problems. Possible explanations for inter-rater discrepancies include potential reporting bias/response shift in parents and/or differences in EF demands across settings. Keywords: Executive function; Pediatric brain tumor; Response shift; Rater bias.
INTRODUCTION Brain tumors account for approximately 20% of all pediatric cancers (Kaatsch, 2010). Advances in treatment have resulted in dramatic increases in survival rates, with the 5-year survival rate for children and adolescents with brain tumors now exceeding 70% (Porter, McCarthy, Freels, Kim, & Davis, 2010). Yet chemotherapy and cranial radiation continue to be necessary treatments for many pediatric brain tumor patients, and neurotoxic effects are well established (Robinson, Fraley, Pearson, Kuttesch, & Compas, 2013). The scope and severity of neuropsychological impairment is linked to multiple treatment-related and individual factors. Processing speed, memory, attention, and executive functions (EF) are particularly vulnerable to the effects of chemotherapy and radiation treatments in children and adolescents with brain tumors (Maddrey et al., 2005; Mulhern et al., 2001; Palmer et al., 2003; Reddick et al., 2003; Ris, Packer, Goldwein, Jones-Wallace, & Boyett, 2001; Spiegler, Boufett, Greenberg, Rutka, & Mabbott, 2004). Younger age at the time of diagnosis, female gender, comorbid
Address correspondence to: Karin S. Walsh, Psy.D., Children’s National Medical Center, 111 Michigan Avenue, NW WP1066, Washington, DC 20010, USA. E-mail: [email protected] (Received 3 March 2014; accepted 28 September 2014)
© 2014 Taylor & Francis
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neurological sequelae (e.g., seizures, hydrocephalus), tumor recurrence, and time since treatment completion have all been shown to be related to greater neuropsychological disruption (Campbell et al., 2007; Jain, Browers, Okcu, Cirino, & Krull, 2009; Krappmann et al., 2007; Macedoni-Luksic, Jereb, & Todorovski, 2003; Merchant et al., 2002). Executive function is a broad neuropsychological domain that encompasses skills related to purposeful, goal-oriented, problem-solving behaviors and self-regulation (Gioia, Isquith, Kenworthy, & Barton, 2002; Lezak, Howieson, & Loring, 2004, p. 35). The development of these functions is largely mediated by frontal brain systems, for which development is protracted, thus increasing susceptibility for disruptions in development. These functions become more salient in later elementary school years and beyond, especially in the remediation of areas of learning weaknesses, and in the independent regulation of behavior. Several models of EF have been proposed since EF was first described by Neisser (1967), and there has been some debate about specific definitions and subcomponents of EF constructs (Burgess, Alderman, Evans, Emslie, & Wilson, 1998; Goldman-Rakic, 1987). This study utilizes a model of EF proposed by Gioia and colleagues (Gioia, Isquith, Guy, & Kenworthy, 2000), which includes two broad EF domains reflecting various components of behavioral/emotional regulation and metacognitive problem-solving skills. Previous research into neuropsychological outcomes in pediatric BT survivors utilizing performance-based tests has documented deficits in attention, processing speed, problem-solving, and metacognitive functions such as WM and strategic planning (Conklin et al., 2012; de Ruiter, van Mourik, Schouten-van Meeteren, Grootenhuis, & Oosterlaan, 2012; Wolfe, Madan-Swain, & Kana, 2012). Executive function deficits among cancer survivors have been linked to negative long-term economic/occupational outcomes, poor emotional health, and worse overall quality of life (Ellenburg et al., 2009; Waber et al., 2006). In a large-scale study, Ness and colleagues (2008) reported that pediatric cancer survivors with EF impairment were less likely to finish high school or be employed, and were at increased risk for emotional difficulties. Performance-based measures are most prevalent in studies evaluating cognitive late effects of cancer treatment, while neuropsychological impairment within home, school, and community settings has received relatively less attention (Campbell, et al., 2007; Peterson et al., 2008). Evaluation of everyday functioning addresses the concept of ecological validity, which refers to the relationship between the patient’s performance on a set of neuropsychological tests and the patient’s behavior in a variety of real world settings (Sbordone, 1996). Although literature provides evidence that traditional paperpencil measures have reasonable ecological validity (Chaytor & Schmitter-Edgecombe, 2003) many qualities of traditional neuropsychological measures limit the amount of variance in everyday skills that can be accounted for, as they are structured tasks administered in a largely controlled context. Thus, measures of everyday functioning may be more sensitive to problems in daily life that are not fully evident in a formal assessment setting (Chevignard, Soo, Galvin, Catroppa, & Eren, 2012). Utilizing parent and teacher ratings of EF in pediatric BT survivors provides an opportunity to capture unique information about their functioning in naturalistic settings. There have been several studies of neuropsychological and behavioral outcomes in survivors of pediatric cancers using behavior rating scales. The most prominent example of such research is being done as part of the Childhood Cancer Survivorship
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Study (CCSS; Ellenburg et al., 2009), which concluded that survivors of CNS malignancy in childhood are at significant risk for impairment in neurocognitive functioning in adulthood, especially if they have received cranial radiation, had a VP shunt placed, or suffered a cerebrovascular incident. Several studies have used the Behavior Rating Inventory of Executive Functioning (BRIEF; Gioia et al., 2000) specifically to examine EF in pediatric cancer survivors (Howarth et al., 2013; Kadan-Lottick et al., 2010; Wolfe et al., 2012). Results from these studies highlighted the presence of various areas of EF disruption in survivors of pediatric cancers, with particular risks associated with radiation treatment, age at diagnosis, age at the time of assessment, intellectual functioning, female gender, hearing impairment, and socioeconomic status (Howarth et al., 2013; Kadan-Lottick et al., 2010). Particular differences in EF between cancer survivors and non-affected comparison groups (i.e., sibling and non-CNS solid tumors) were documented in the areas of working memory (Howarth et al., 2013), task efficiency, memory, and emotional regulation (Kadan-Lottick et al., 2010). Research has also demonstrated the importance of EF in social functioning in survivors of pediatric brain tumors (Wolfe et al., 2012). To our knowledge, only one study to date has compared ratings from parents and teachers in this population of children, specifically related to response to methylphenidate treatment, and the results indicated only modest agreement between raters (Nelson et al., 2010). Our primary aim was to compare EF in childhood cancer survivors compared to same-aged healthy children (HC) by parent and teacher ratings on the Behavior Rating Inventory of Executive Function (BRIEF). As previous research shows EF deficits following treatment of pediatric CNS cancers (De Luca, Conroy, McCarthy, Anderson, & Ashley, 2009), we hypothesized that pediatric BT survivors would demonstrate higher mean parent and teacher ratings of executive dysfunction compared to HC. We also predicted a higher frequency of clinically elevated symptoms in the BT group compared to HC. Finally, we predicted that teacher ratings would reflect greater executive dysfunction in BT survivors compared to parent ratings, as the academic environment is often inherently more demanding on the EF system (Hartman, Rhee, Willcutt, & Pennington, 2007; Mares, McLuckie, Schwartz, & Saini, 2007).
METHOD All data included in this manuscript were obtained in compliance with the regulations of our institution and approved by the Institutional Review Board. Participants and procedures This is a retrospective, cross-sectional study of 62 pediatric BT survivors evaluated in our clinic between 2002 and 2013 (mean age = 12.02; SD = 3.56) and 62 age- and gender-matched HC (mean age = 11.79; SD = 3.21). Participant disease and treatment characteristics of the BT group were obtained via review of available medical records (Table 1). The BT and HC samples were nearly equal in gender representation (BT male = 30, 48.6%; female = 32, 51.6%; HC male = 31, 50%; female = 31; one BT/HC pair could not be matched on gender). BT survivors were included in the study if they were age 6 to 18 at assessment, had undergone chemotherapy and/or radiation
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G. C. WOCHOS ET AL. Table 1. Diagnostic characteristics of brain tumor sample Disease/treatment characteristics (N = 62)
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Age at diagnosis
Time since treatment Tumor type Medulloblastoma Ependymoma Astrocytoma Glioma Germinoma Craniopharyngioma Other tumor types Tumor recurrence* Yes No Treatment type Surgery + Chemotherapy + Radiation Chemotherapy Only Radiation Only Chemo+ Radiation Surgery+ Chemotherapy Surgery + Radiation Hydrocephalus* Yes No Seizures* Yes No Cerebellar Mutism* Yes No
Mean (SD) Range 5.81 (3.94) 1–14 years 4.68 (3.72) 0.30–15 years Frequency (%) 18 (29.0) 10 (16.1) 9 (15.5) 7 (11.3) 7 (11.3) 2 (3.2) 9 (14.5) 23 (37.1) 39 (62.9) 31 (50) 5 (8.1) 5 (8.1) 7 (11.3) 7 (11.3) 7 (11.3) 16 (25.8) 46 (74.2) 8 (12.9) 54 (87.1) 5 (8.1) 57 (91.9)
*Characteristics were historical, not present at the time of neuropsychological assessment.
treatment, and were off treatment and in remission/with stable disease. A total of 35 potential participants were excluded for not meeting inclusion criteria. Following completion of their treatment, each participant was clinically referred by their treatment team for a comprehensive neuropsychological assessment within the Division of Neuropsychology. Each neuropsychological assessment included parent and teacher-reported questionnaires of EF (BRIEF; Gioia et al., 2000). Of the 62 BT participants with a parent BRIEF, 50 also had a teacher BRIEF. Participants in the HC comparison group were selected from the original BRIEF normative sample and recruited from urban, sub-urban, and rural Maryland private and public schools, reflecting 1999 U.S. Census estimates for socioeconomic status, ethnicity, and gender distribution. Participants were excluded from inclusion in the normative sample if they had any history of learning (special education) or psychiatric impairment
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(prescribed psychotropic medication; Gioia et al., 2000). A recent meta-analysis demonstrated geographic equipoise (national and international), addressing recent concerns about heightened sensitivity of the BRIEF associated with sampling of the original standardization sample (Roth, Erdodi, McCulloch, & Isquith, 2014).
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Instruments and measures The BRIEF is a standardized questionnaire assessing EF by rating a child’s everyday behavior (Gioia et al., 2000). The BRIEF consists of 86 questions that contribute to eight EF domains comprising two indices: Behavioral Regulation and Metacognition. BRIEF domains and associated scale descriptions are presented in Table 2. Higher scores indicate greater impairment, with t-scores ≥ 65 indicating clinically significant symptomatology. Validity and test–retest reliability are well established (r = .82 for parents and .88 for teachers) with moderate correlations between teacher and parent ratings (r = .32–.34; Gioia et al., 2000). The BRIEF has been shown to demonstrate sensitivity to executive dysfunction in children with various developmental and acquired neurological disorders (Mautz et al., 2002). Data analysis Prior to data analysis, validity scales were checked for elevations (e.g., Negativity and Inconsistency scales) with no significant elevations identified in the sample. A profile analysis was conducted as mixed repeated-measures MANOVA to examine group Table 2. Description of BRIEF scales Scale
Behavioral description
Behavioral regulation Inhibit
Impulse control; ability to inhibit behaviors when necessary
Shift
Flexibility; mental flexibility in problem-solving; moving easily between situations, activities, or problems as needed
Emotional Control Metacognitive Initiate
Ability to modulate emotional responses appropriately
Working Memory
Ability to hold information in mind in order to complete a task and/or stay with an activity
Plan/Organize
Planning and organizational skills; Ability to anticipate future events, set goals; strategically plan and organize steps to complete tasks; understand and communicate key information
Organization of Materials
Ability to keep materials and environment orderly
Monitor
Self-monitoring; Ability to check and assess performance toward a goal; awareness of effects of one’s own behavior on others
Self-starting; Independently initiate tasks or activities; independently generate ideas
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differences across executive function domains. Scores on the eight BRIEF subscales served as within-participants variables, while group assignment (BT v. HC) served as the between-participants variable. We ran separate MANOVAs for Parent and Teacher BRIEF ratings. The Greenhouse-Geisser statistic was used in all analyses to control for violation of the sphericity assumption. To examine rater differences in the BT group, a repeated-measures MANOVA with two within-participants factors (rater and BRIEF subscales) was applied. Post-hoc paired-samples t-tests were run on those BRIEF subscales that were statistically significant in the MANOVA. Dichotomous variables were created to analyze clinically significant impairments. Each subscale was coded as: T ≤ 64 = 0, and T ≥ 65 = 1. Chi square was conducted to examine the frequencies of clinical elevations in each group (BT vs. HC) across BRIEF scales, and odds ratios (OR) were derived. In order to evaluate the frequencies of clinical elevations in the BT group between raters (parent vs. teacher), McNamar statistics were used. Finally, Pearson bivariate correlations were run to explore relationships between BRIEF scores with disease and treatment factors previously shown to be associated with neuropsychological impairment. Probability value was set at p < .05 for all analyses. We used Ferguson’s (2009) “recommended minimum effect size representing a ‘practically’ significant effect for social science data” (RMPE; Ferguson, 2009, p. 533), which suggests .04 for squared association indices (e.g., Eta-squared) and 2.0 for risk estimates (e.g., OR). We also applied Ferguson’s odds ratio effect size interpretations of moderate (OR ≥ 3.0) and strong (OR ≥ 4.0), when appropriate.
RESULTS Parent profile analysis Parent-rated EF did not reveal a statistically significant main effect for group or EF scale. However, there was a statistically significant group × EF interaction, F(4.93) = 3.12, p = .009, Eta2 = .025. Working memory (WM) was the only domain rated by parents as significantly higher in the BT group compared to the HC group, F(1) = 7.79, p = .006, Eta2 = .06, although the mean score is within the normal range for age (Figure 1). Further, examining the relationship between clinically elevated symptom levels (T ≥ 65) and group on parent rating indicated statistically significant differences on the Shift scale (χ2 = 4.21, p = .04), for which 16.1% of the BT survivors were clinically elevated (Figure 2). Parents of BT survivors were nearly four times more likely to report clinically significant inflexibility compared to parents of HCs (Table 3). Teacher profile analysis Teacher-rated EF revealed a significant main effect for group, F(1) = 14.51, p = .000, Eta2 = .117, and a significant group × EF interaction, F(3.53) = 4.19, p = .004, Eta2 = .037. The main effect for EF was not statistically significant, F(3.53) = 4.19, p = .173 Eta2 = .015. Mean teacher ratings in the BT group were significantly higher (i.e., greater impairment) than those for the HC comparison group in seven of the eight
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Figure 1. Mean scores on the BRIEF by parent and teacher reports for the brain tumor and healthy control groups.
Figure 2. Frequency of clinical elevations on scales of the BRIEF by group and rater.
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Table 3. Differences in proportions of the clinically elevated symptoms by group and rater
Parent profile analysis (brain tumor v healthy controls) (N = 62) Inhibit Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor Teacher profile analysis (brain tumor v healthy controls) (N = 50) Inhibit* Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor Rater profile analysis (parent v teacher) (N = 50)** Inhibit Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor
Statistic (chi square)
Sign. (p)
Odds ratio (T ≥ 65)
95% confidence interval
.00 4.21 .90 .32 1.86 .89 1.97 .00
1.00 .04 .34 .57 .17 .34 .16 1.00
1.00 3.78 1.85 0.72 1.88 1.63 2.38 1.00
0.27–3.64 0.99–14.49 0.51–6.66 0.24–2.22 0.75–4.69 0.59–4.54 0.69–8.18 0.33–3.04
0.48 7.28 4.98 15.08 19.78 11.08 3.11 1.65
.49 .01 .03 .00 .00 .00 .06 .20
1.55 3.70 3.41 6.52 10.32 4.82 2.37 1.83
0.45–5.43 1.38–9.91 1.11–10.48 2.37–17.95 3.24–32.88 1.82–12.73 0.89–6.29 0.72–4.61
0.80 3.06 4.90 12.19 4.92 7.56 4.92 4.92
.38 .08 .02 .00 .02 .00 .02 .02
21.50 2.50 12.33 1.42 12.27 5.18 3.18 3.18
1.58–292.38 0.54–11.65 1.14–132.94 0.18–10.99 2.31–65.34 0.89–30.09 0.40–25.31 0.40–25.31
*Fisher Test Statistic was used because the minimum expected cell count requirement was not met. **McNemar NPAR statistic.
domains (Shift, Emotional Control, Initiate, WM, P/O, Organization of Materials, and Monitor), with effect sizes ranging from .01 to .21 (Figure 1). The relationship between clinically elevated symptoms (T ≥ 65) and group on teacher rating revealed statistically significant differences on five of the BRIEF scales including Shift (26% clinically elevated), Emotional Control (19%), Initiate (34%), WM (34%), and P/O (31%; Figure 2). Moderate to strong odds ratios emerged across these scales (Table 3). Rater profile analysis (BT only) As inter-rater reliability has been shown to be lower between parents and teachers (Achenbach, McConaughy, & Howell, 1987) and the normative sample for the BRIEF reported only modest correlations between parent and teacher ratings (Global Executive Composite [GEC], r = .340; Gioia et al., 2000), we examined the correlations within our sample and found greater consistency between parent and teacher ratings than
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reported for the normative sample (GEC r = .572; Metacogniton Index [MCI] r = .570; Behavior Regulation Index [BRI] r = .589). Intraclass correlations, however, did not meet minimum standards of agreement (ICC GEC r = .581). Comparing EF ratings from parents and teachers in the BT group revealed a significant main effect for rater (parent versus teacher); F(1, 49) = 21.57, p = .000, Eta2 = .306. There was also a significant main effect for EF, F(7, 48) = 7.84, p = .000, Eta2 = .561, but no significant rater by EF interaction effect (Figure 1). There were statistically significant differences across all eight EF domains such that teacher ratings were significantly higher than parent ratings for BT survivors (Table 4). All eight scale differences were modest, but met Ferguson’s (2009) RMPE odds ratio criteria. McNemar analyses of reported clinical elevations in the BT group by parents and teachers revealed statistically significant rater differences on six of the eight BRIEF scales (EC, Initiate, WM, P/O, Organization of Material, and Monitor). Effect sizes ranged from weak to strong (OR 1.42–12.33), and 95% Confidence Intervals suggest that this is likely driven by a few very impaired children (Table 3), which is consistent with the fact that overall mean scores in the BT group do not reach a level of clinical significance. Disease and treatment-related factors potentially associated with EF in the BT group were also examined. Clinically elevated EF was not found to be associated with age at diagnosis, tumor location, or a history of hydrocephalus, seizures, or cerebellar mutism syndrome. Elevated ratings on the P/O scale were significantly associated with the age at time of testing (r2 = .213, p = .048) and the time since treatment (r2 = .353, p = .005) by parents only. Elevations on the EC scale were significantly associated with having radiation therapy, again by parents only (r2 = .235, p = .033). Statistically significant relationships from teacher ratings were found with tumor recurrence and Table 4. Rater comparison in brain tumor group Parent (N = 62)
Teacher (N = 50)
Statistic (t)
Sign. (p)
Effect size (Cohen’s d)
M (SD)
Range
M (SD)
Range
Initiate
48.31 (9.69)
37–84
52.02 (9.52)
42–81
–3.27
.002
.47
Shift
52.55 (13.85)
36–92
59.52 (18.58)
42–111
–2.93
.005
.45
Emotional Control
49.74 (11.61)
36–83
56.28 (14.59)
44–101
–4.69
.000
.60
Initiate
51.68 (10.08)
35–83
58.80 (13.43)
41–81
–3.98
.000
.64
Working Memory
55.71 (11.14)
38–87
62.06 (16.54)
38–106
–3.21
.002
.46
Plan/Organize
53.63 (11.25)
37–84
60.30 (14.92)
42–104
–4.12
.000
.55
Organization of Materials
50.23 (10.95)
33–73
60.36 (21.81)
42–129
–3.48
.001
.62
Monitor
52.23 (12.34)
31–93
57.82 (14.57)
40–102
–2.99
.004
.51
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treatment with intrathecal chemotherapy. Specifically, clinical elevations on the Initiate (r2 = .375, p = .004), WM (r2 = .290, p = .020), P/O (r2 = .271, p = .028), and Monitor (r2 = .315, p = .013) scales were associated with the presence of tumor recurrence. Treatment with intrathecal chemotherapy was significantly related to elevations on the Shift (r2 = .282, p = .048), EC (r2 = .350, p = .018), and Organization of Materials (r2 = .302, p = .037) scales. Chi square analysis of the significant correlations above did not support a significant relationship on parent report between impaired planning and organization with age at testing or the amount of time since treatment completion. Nor was a significant relationship demonstrated between parent ratings of emotional dysregulation and radiation therapy. Significant bivariate correlations between teacher rated impairments with flexibility and organizing materials was not confirmed with chi square analysis. However, statistically significant relationships between tumor recurrence and teacher rated clinical impairments in initiation (Initiate 67% elevated; χ2 = 7.03, p = .008, Eta2 = .375), working memory (61% elevated; χ2 = 4.22, p = .040, Eta2 = .290), and self-monitoring (Monitor 44% elevated; χ2 = 4.97, p = .026, Eta2 = .315) were found.
DISCUSSION We aimed to compare EF in BT survivors and typically developing peers in their naturalistic settings (e.g., home and school). Consistent with previous literature, our results demonstrated that BT survivors exhibit various EF late effects, although these deficits appear to be most functionally disruptive in the formal learning environment (i.e., teacher ratings). Parents indicated WM to be the domain that significantly differed between survivors and their healthy peers, similar to the recent findings by Howarth and colleagues (2013). While as a group they did not exhibit clinically significant impairments in WM, nearly a quarter (24%) of the sample showed clinical impairment. Parents indicated a higher rate of clinically elevated problems associated with flexibility in the survivors, nearly four times that of typically developing children. Flexibility and WM limitations have been demonstrated in survivors previously (Maddrey et al., 2005; Palmer et al., 2003; Reddick et al., 2003; Ris et al., 2001; Robinson et al., 2013; Spiegler et al., 2004), as have other higher-order cognitive problems, although those did not emerge in our parent ratings. Teacher ratings, however, indicated more global and intense EF problems in a proportion of BT survivors than parent ratings. Nearly all areas of EF were significantly higher in BT survivors compared to HC, although again, average levels of the group as a whole were not significantly elevated. However, survivors were more likely to exhibit poor WM, problems with initiation, flexibility, and planning and organizational skills. Rates of functionally impairing difficulties in these areas ranged from three to more than ten times that of typically developing peers, with 26–34% exhibiting clinically significant problems. Similar inter-rater discrepancies have been documented in other pediatric clinical populations as well, including children with Attention-Deficit/ Hyperactivity Disorder (ADHD; Mares et al., 2007) and intellectual disability (Deb, Dhaliwal, & Roy, 2008; Nelson et al., 2010), highlighting the need for multimodal assessment. However, the pattern of inter-rater differences observed in our sample directly contrasts with previous findings reported in the BRIEF normative sample, as
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well as previous literature comparing parent and teacher ratings, which shows that parents consistently rate significantly greater EF difficulties than teachers (Gioia et al., 2000; Offord et al., 1996). Working memory and flexibility appear to be particularly vulnerable functional areas for disruption in some pediatric BT survivors. Teachers alone highlight significant problems with survivors’ ability to independently initiate tasks in a strategic and organized manner, and that insight into their difficulties and an ability to adjust their approach and develop novel strategies is also limited. These may be skills that are more in demand within the learning environment than in the home or social settings. The school environment places high demands on the executive system, as students are required to engage and sustain attention for extended periods of time, manage and manipulate novel information, develop solutions to various problems, and demonstrate their knowledge efficiently and effectively, with increasing independence over time. Differences in environmental demand and expectations are but one explanation for the discrepancy between parent and teacher ratings. Alternatively, parents of survivors may naturally adjust to their child’s needs and provide a higher, more individualized level of support around EF difficulties, diminishing how functionally disruptive such problems are in the home setting. Altered (diminished) expectations by parents following diagnosis and treatment of a brain tumor in one’s child may also contribute to these observed differences. For example, several studies have identified response bias and a tendency to minimize negative mood symptoms and deny quality of life difficulties on self-report measures among adolescent and adult cancer survivors (Bauld, Anderson, & Arnold, 1998; Canning, Canning, & Boyce, 1992; O’Leary, Diller, & Recklitis, 2007). Such findings are consistent with social desirability theory, whereby cancer survivors, by means of adaptive self-preservation following their cancer experience, emphasize positive personal traits and minimize negative symptoms. Shelder, Mayman, and Manis (1993) also argue that a positive illusory bias may be a psychosocial risk-factor for survivors of various medical illnesses. Similarly, Sprangers and Schwartz (1999) described a phenomenon of response shift in the assessment of quality of life outcomes, in which patients confronted with a life-threatening illness change or “recalibrate” their internal standards of measurement with regard to quality of life on self-report measures. This might also apply to parent’s standards for evaluating their child’s functioning in response to the diagnosis and treatment of such a significant medical event, potentially explaining the minimal symptoms of executive dysfunction endorsed by parents compared to teachers. This study is, to our knowledge, the first to compare everyday EF in pediatric BT survivors to typically developing peers across multiple environments and raters. This cross-validation of EF between different respondents provides a more comprehensive view of a child’s real-world functioning, and assesses a broad range of dynamic EF skills in different contexts using a single instrument. Our results highlight an important practical matter—that utilization of a single instrument from a single rater to determine neuropsychological functioning might not be adequate in this particular patient population—even as a screening tool to help identify alterations in neuropsychological functioning over time. In addition, while previous studies have reported an unexpected response bias/shift on self-report measures in cancer survivors, our findings raise similar concerns regarding parent report in younger survivors. These findings highlight a need for further research in this area.
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Our examination of disease and treatment-related factors that may relate to EF impairment in BT survivors produced mixed results. Previous literature indicates that factors associated with poorer neuropsychological outcomes in this population include tumor location (Mulhern, Hancock, Fairclaugh, & Kun, 1992), age at diagnosis (Sands et al., 2001) and radiation treatment (Reamers et al., 2003). Our results indicate that there might be an association between tumor recurrence, treatment with radiation and/or intrathecal chemotherapy, the time since completion of treatment, and the age of the child when evaluated and greater risk of some EF impairments. However, only tumor recurrence was associated with a higher proportion of survivors being rated by teachers as having clinically significant impairments in working memory, self-starting, and selfawareness. The lack of expected convergence with prior literature might have to do with the fact that the majority of prior research has been based on performance-based measures of EF in the lab setting, while this study focused on ratings of real-world EF across multiple environments within which survivors are engaged. Several limitations and considerations for future research bear mention. Interpretation of the findings of this study must consider the limitations inherent to retrospective, cross-sectional research. The participants were clinically referred, resulting in the possibility of sample bias toward a more impaired sample. In addition, the BT sample itself was heterogeneous with regard to disease and treatment characteristics (e.g., tumor and treatment type), disease/treatment complications (e.g., tumor recurrence, presence of cerebellar mutism, hydrocephalus, or seizures), and disease/treatment specific demographic variables (e.g., age at diagnosis and treatment, time since treatment). This complicates the ability to generalize to the pediatric BT population more globally, although we did examine these variables, which allowed some characterization of the sample of EF-impaired children. Additional limits to generalizability include our inability to match participants on socio-economic status or global cognitive abilities (e.g., intelligence), the absence of additional BT sample demographic variables that might influence parent ratings (e.g., parent education level and employment status, special education status, grade retention), the use of a single behavior rating scale, as well as the inherent flaws associated with rating scales (e.g., relying on a third party for ratings of a child’s behavior, potential for rater bias as previously discussed above). Nonetheless, our results further support the importance of individualized neuropsychological assessment and cross validation of EF measures in BT survivors following treatment, as at least a subset of survivors exhibit disruptions in typical EF development that impacts their daily functioning.
REFERENCES Achenbach, T., McConaughy, S., & Howell, C. (1987). Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity. Psychological Bulletin, 101, 213–232. Bauld, C., Anderson, V., & Arnold, J. (1998). Psychosocial aspects of adolescent cancer survival. Journal of Pediatrics and Child Health, 34, 120–126. Burgess, P. W., Alderman, N., Evans, J., Emslie, H., & Wilson, B. A. (1998). The ecological validity of tests of executive function. Journal of the International Neuropsychological Society, 4, 547–558.
Downloaded by [University of California, San Diego] at 23:58 11 January 2015
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Campbell, L. K., Scaduto, M., Sharp, W., Dufton, L., Van Slyke, D., & Compas, B. (2007). A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatric Blood and Cancer, 49, 65–73. Canning, E. H., Canning, R. D., & Boyce, W. T. (1992). Depressive symptoms and adaptive style in children with cancer. Journal of the American Academy of Child and Adolescent Psychiatry, 31, 1120–1124. Chevignard, M. P., Soo, C., Galvin, J., Catroppa, C., & Eren, S. (2012). Ecological assessment of cognitive functions in children with acquired brain injury: A systemic review. Brain Injury, 26, 1033–1057. doi:10.3109/02699052.2012.666366 Chaytor, N., & Schmitter-Edgecombe, M. (2003). The ecological validity of everyday neuropsychological tests: A review of the literature on everyday cognitive skills. Neurospychology Review, 13, 191–197. doi:10.1023/B:NERV.0000009483.91468.fb Conklin, H. M., Ashford, J. M., Howath, R. A., Merchant, T. E., Ogg, R. J., Santana, V. M., . . . Xiong, X. (2012). Working memory performance among childhood brain tumor survivors. Journal of the International Neuropsychological Society, 18, 996–1005. Deb, S., Dhaliwal, A. J., & Roy, M. (2008). The usefulness of conners’ rating scales-revised in screening for attention deficit hyperactivity disorder in children with intellectual disabilities and borderline intelligence. Journal of Intellectual Disability Research, 52, 950–965. De Luca, C. R., Conroy, R., McCarthy, M. C., Anderson, V. A., & Ashley, D. M. (2009). Neuropsychological impact of treatment with brain tumors. Cancer Treatment Resources, 150, 277–296. doi:10.1007/b109924_17 de Ruiter, M. A., van Mourik, R. V., Schouten-van Meeteren, A. Y. N., Grootenhuis, M. A., & Osterlaan, J. O. (2012). Neurocognitive consequences of a pediatric brain tumour and its treatment: A meta-analysis. Developmental Medicine & Child Neurology, 55, 408–417. Ellenberg, E., Liu, Q., Gioia, G., Yasui, Y., Packer, R. J., Mertens, A., . . . Zeltzer, L. K. (2009). Neurocognitive status in long-term survivors of CNS malignancies: A report from the childhood cancer survivor study. Neuropsychology, 23, 705–717. doi:10.1037/a0016674 Ferguson, C. J. (2009). An effect size primer: A guide for clinicians and researchers. Professional Psychology: Research and Practice, 40, 532–538. Gioia, G. A., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000). Behavior rating inventory of executive function. Odessa, FL: Psychological Assessment Resources. Gioia, G. A., Isquith, P. K., Kenworthy, L., & Barton, (2002). Profiles of everyday executive function in acquired and developmental disorders. Child Neuropsychology, 8, 121–137. Goldman-Rakic, P. (1987). Circuitry of primate pre-frontal cortex and regulation of behavior by representational memory. In F. Plum (Ed.), Handbook of physiology: The nervous system (pp. 373–417). New York, NY: Oxford University Press. Hartman, C. A., Rhee, S. H., Willcutt, E. G., & Pennington, B. F. (2007). Modeling rater agreement for ADHD: Are parents or teachers biased? Journal of Abnormal Child Psychology, 35, 536–542. Howarth, R. A., Ashford, J. M., Merchant, T. E., Ogg, R. J., Santana, V., Shengjie, W., . . . Conklin, H. M. (2013). The utility of parent report in assessment of working memory among child brain tumor survivors. Journal of the International Neuropsychological Society, 19, 380–389. doi:10.1017/S1355617712001567 Jain, N., Browers, P., Okcu, M. F., Cirino, P. T., & Krull, K. R. (2009). Sex specific attention problems in long-term survivors of pediatric acute lymphoblastic leukemia. Cancer, 115, 4238–45. Kaatsch, P. (2010). Epidemiology of childhood cancer. Cancer Treatment Reviews, 36, 277–285. doi:10.1016/j.ctrv.2010.02.003 Kadan-Lottick, N. S., Zeltzer, L. K., Lui, Q., Yasui, Y., Ellenberg, L., & Gioia, G., . . . Krull, K. R. (2010). Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers. Journal of the National Cancer Institute, 102, 881–893. doi:10.1093/jcni/ djq156
Downloaded by [University of California, San Diego] at 23:58 11 January 2015
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Krappmann, P., Paulides, M., Stohr, W., Ittner, E., Plattig, P., & Nickel, P.,... Langer, T. (2007). Almost normal cognitive function in patients during therapy for childhood acute lymphoblastic leukemia without cranial irradiation according to ALL-BFM 95 and COALL 06-97 protocols: Results of an Austrian-German multicenter longitudinal study and implications for follow-up. Pediatric Hematology and Oncology, 24, 101–109. Lezak, M. D., Howieson, D. B., & Loring, D. W. (2004). Neuropsychological assessment (4th ed.). New York, NY: Oxford University Press. Macedoni-Luksic, M., Jereb, B., & Todorovski, L. (2003). Long-term sequelae in children treated for brain tumors: Impairments, disability, and handicap. Pediatric Hematology. Oncology, 20, 89–101. Maddrey, A. M., Bergeron, J. A., Lombardo, E. R., McDonald, N. K., Mulne, A. F., Barenburg, P. D., & Bower, D. C. (2005). Neuropsychological performance and quality of life of 10 year survivors of childhood medulloblastoma. Journal of Neurooncology, 72, 245–253. doi:10.1007/s11060-004-3009-z Mares, D., McLuckie, A., Schwartz, M., & Saini, M. (2007). Executive function impairments in children with attention-deficit hyperactivity disorder: Do they differ between school and home environments? Canadian Journal of Psychiatry, 52, 527–534. Mautz, W., Carpentieri, S., Shapiro, B., Dalton, V., Gelber, R., Sallan, S., et al. (2002). Absence of progression of cognitive sequelae 4 to 7 years after CRT for ALL [Abstract]. Journal of the International Neuropsychological Society, 8, 292. Merchant, T. E., Kiehna, E. N., Miles, M. A., Zhu, J., Xiong, X., & Mulhern, R. K. (2002). Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors. International Journal of Radiation Oncology Biology Physics, 53, 1271–1278. Mulhern, R. K., Hancock, J., Fairclaugh, D., & Kun, L. (1992). Neuropsychological status of children treated for brain tumors: A critical review and integrative analysis. Medical and Pediatric Oncology, 20, 181–191. Mulhern, R. K., Palmer, S. L., Reddick, W. E., Glass, J. O., Kun, L. E., & Taylor, J., . . . Gajjar, A. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. Journal of Clinical Oncology, 19, 472–479. Neisser, U. (1967). Cognitive psychology. New York, NY: Appleton-Century-Crofts. Ness, K. K., Gurney, J. G., Zeltzer, L. K., Leisering, W., Mulrooney, D. A., Nathan, P. C., … Mertens, A. C. (2008). The impacts of limitations on physical, executive, and emotional function on health-related quality of life among adult survivors of childhood cancer: A report for the childhood cancer survivor study. Archives of Physical Medicine and Rehabilitation, 89, 128–136. Nelson, K. L., Conklin, H. M., Ashford, J. M., Kahalley, L. S., Wu, S., & Xiong, X. (2010). Parent and teacher ratings of attention during a year-long methylphenidate trial in children treated for cancer. Journal of Pediatric Psychology, 26, 438–450. Offord, D. R., Boyle, M. H., Racine, Y., Szatmari, P., Fleming, J. E., Sanford, M., & Lipman, E. L. (1996). Integrated assessment data from multiple informants. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1078–1085. O’Leary, T. E., Diller, L., & Recklitis, C. J. (2007). The effects of response bias on self-reported quality of life among childhood cancer survivors. Quality of Life, 16, 1211–1220. Palmer, S. L., Gajjar, A., Reddick, W. E., Glass, J. O., Kun, L. E., & Wu, S. (2003). Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology, 17, 548–555. doi:10.1037/ 0894-4105.17.4.548 Peterson, C. C., Johnson, C. E., Ramirez, J. Y., Huestis, S., Pai, A. L., Demaree, H. A., & Drotar, D. (2008). A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia. Pediatric Blood Cancer, 51, 9–104.
Downloaded by [University of California, San Diego] at 23:58 11 January 2015
EXECUTIVE DYSFUNCTION IN BRAIN TUMOR SURVIVORS
1257
Porter, K. R., McCarthy, B. J., Freels, S., Kim, Y., & Davis, F. G. (2010). Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology. Neuro Oncology, 12, 520–527. doi:10.1093/neuonc/nop066 Reamers, T. S., Ehrenfels, S., Mortensen, E. L., Schmiegelow, M., Sonderkaer, S., Carstensen, H., … Muller, J. (2003). Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors. Medical and Pediatric Oncology, 40, 26–34. Reddick, W. E., White, H. A., Glass, J. O., Wheeler, G. C., Thompson, S. J., & Gajjar, A., . . . Mulhern, R. K. (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric deficits in pediatric brain tumor survivors. Cancer, 15, 2512–2519. doi:10.1002/cncr.11355 Ris, D. M., Packer, R., Goldwein, J., Jones-Wallace, D., & Boyett, J. M. (2001). Intellectual outcome after reduced dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: A Children’s Cancer Group study. Journal of Clinical Oncology, 19, 3470–3476. Robinson, K. E., Fraley, C. E., Pearson, M. M., Kuttesch, J. F., & Compas, B. E. (2013). Neurocognitive late effects of pediatric brain tumors of the posterior fossa: A quantitative review. Journal of the International Society of Neuropsychology, 19, 44–53. doi:10.1017/ S135561712000987 Roth, R. M., Erdodi, L. A., McCulloch, L. J., & Isquith, P. K. (2014). Much ado about norming: The Behavior Rating Inventory of Executive Function. Child Neuropsychology. [Epub ahead of print] PubMed PMID: 24650292. Sands, S. A., Kellie, S. J., Davidow, A. L., Diez, B., Villablanca, J., Weiner, H. I., … Finlay, J. L. (2001). Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: From the First International CNS Germ-Cell Tumor Study. Neuro-Oncology, 3, 175–183. Sbordone, R. J. (1996). Ecological validity: Some critical issues for the neuropsychologist. In R. J. Sbordone & C. J. Long (Eds.), Ecological validity of neuropsychological testing (pp. 15–41). Delray Beach, FL: GR Press/St. Lucie Press. Shelder, J., Mayman, M., & Manis, M. (1993). The illusion of mental health. The American Psychologist, 48, 1117–1131. Spiegler, B. J., Boufett, E., Greenberg, M. L., Rutka, J. T., & Mabbott, D. J. (2004). Change in neurocognitive functioning after treatment with cranial radiation in childhood. Journal of Clinical Oncology, 22, 706–713. doi:10.1200/JCO.2004.05.186 Sprangers, M. A. G., & Schwartz, C. E. (1999). Integrating response shift into health-related quality of life research: A theoretical model. Social Science & Medicine, 48, 1507–1515. Waber, D. P., Pomeroy, S. L., Chiverton, A. M., Kieran, M. W., Scott, R. M., Goumnerova, L. C., & Rivkin, M. J. (2006). Everyday cognitive function after craniopharyngioma in childhood. Pediatric Neurology, 34, 13–19. doi:10.1016/j.pediatrneurol.2005.06.002 Wolfe, K. R., Madan-Swain, A., & Kana, K. (2012). Executive dysfunction in pediatric posterior fossa tumor survivors: A systematic literature review of neurocognitive deficits and intervention. Developmental Neuropsychology, 37, 153–175. Wolfe, K. R., Walsh, K. S., Reynolds, N. C., Mitchell, F., Reddy, A. T., Paltin, I., & Madan-Swain, A. (2012). Executive functions and social skills in survivors of pediatric brain tumor. Child Neurosychology iFirst, 1–15, doi:10.1080/09297049.2012.669470
The Clinical Neuropsychologist Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ntcn20
Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors a
G. C. Wochos , C. H. Semerjian a
ac
ab
& K. S. Walsh
Children’sNational Medical Center, Washington, DC 20010, USA
b
The George Washington University Medical Center, Washington, DC 20052, USA c
Roosevelt University, Chicago, IL 60605, USA Published online: 24 Oct 2014.
Click for updates To cite this article: G. C. Wochos, C. H. Semerjian & K. S. Walsh (2014) Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors, The Clinical Neuropsychologist, 28:8, 1243-1257, DOI: 10.1080/13854046.2014.971875 To link to this article: http://dx.doi.org/10.1080/13854046.2014.971875
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The Clinical Neuropsychologist, 2014 Vol. 28, No. 8, 1243–1257, http://dx.doi.org/10.1080/13854046.2014.971875
Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors G. C. Wochos1, C. H. Semerjian1,3, and K. S. Walsh1,2 1
Children’sNational Medical Center, Washington, DC 20010, USA The George Washington University Medical Center, Washington, DC 20052, USA 3 Roosevelt University, Chicago, IL 60605, USA
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2
We aimed to compare executive function (EF) outcomes in pediatric brain tumor (BT) survivors compared with healthy children (HC) across multiple settings. This retrospective cross-sectional study of BT survivors and age- and gender-matched HC analyzed scale patterns of parent and teacher ratings of EF (Behavior Ratings of Executive Function; BRIEF). We also analyzed relationships between groups and raters (parent/teacher) and clinical elevations across EF domains on the BRIEF. Group differences in aspects of EF emerged from parent ratings in working memory (WM), while significant interactions from teacher ratings emerged on nearly all EF scales. Parents reported impaired cognitive/behavioral flexibility in the BT group four times more than parents of HC. Teachers rated survivors significantly more poorly as a group on the majority of EF domains, and indicated clinical impairment in cognitive/behavioral flexibility, emotional regulation, self-starting/initiation, WM, and planning and organization (P/O) four to ten times more often than the teachers of HC. Overall, teacher ratings of EF impairment in pediatric BT survivors were significantly greater than parent ratings, who reported far fewer EF problems. Possible explanations for inter-rater discrepancies include potential reporting bias/response shift in parents and/or differences in EF demands across settings. Keywords: Executive function; Pediatric brain tumor; Response shift; Rater bias.
INTRODUCTION Brain tumors account for approximately 20% of all pediatric cancers (Kaatsch, 2010). Advances in treatment have resulted in dramatic increases in survival rates, with the 5-year survival rate for children and adolescents with brain tumors now exceeding 70% (Porter, McCarthy, Freels, Kim, & Davis, 2010). Yet chemotherapy and cranial radiation continue to be necessary treatments for many pediatric brain tumor patients, and neurotoxic effects are well established (Robinson, Fraley, Pearson, Kuttesch, & Compas, 2013). The scope and severity of neuropsychological impairment is linked to multiple treatment-related and individual factors. Processing speed, memory, attention, and executive functions (EF) are particularly vulnerable to the effects of chemotherapy and radiation treatments in children and adolescents with brain tumors (Maddrey et al., 2005; Mulhern et al., 2001; Palmer et al., 2003; Reddick et al., 2003; Ris, Packer, Goldwein, Jones-Wallace, & Boyett, 2001; Spiegler, Boufett, Greenberg, Rutka, & Mabbott, 2004). Younger age at the time of diagnosis, female gender, comorbid
Address correspondence to: Karin S. Walsh, Psy.D., Children’s National Medical Center, 111 Michigan Avenue, NW WP1066, Washington, DC 20010, USA. E-mail: [email protected] (Received 3 March 2014; accepted 28 September 2014)
© 2014 Taylor & Francis
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neurological sequelae (e.g., seizures, hydrocephalus), tumor recurrence, and time since treatment completion have all been shown to be related to greater neuropsychological disruption (Campbell et al., 2007; Jain, Browers, Okcu, Cirino, & Krull, 2009; Krappmann et al., 2007; Macedoni-Luksic, Jereb, & Todorovski, 2003; Merchant et al., 2002). Executive function is a broad neuropsychological domain that encompasses skills related to purposeful, goal-oriented, problem-solving behaviors and self-regulation (Gioia, Isquith, Kenworthy, & Barton, 2002; Lezak, Howieson, & Loring, 2004, p. 35). The development of these functions is largely mediated by frontal brain systems, for which development is protracted, thus increasing susceptibility for disruptions in development. These functions become more salient in later elementary school years and beyond, especially in the remediation of areas of learning weaknesses, and in the independent regulation of behavior. Several models of EF have been proposed since EF was first described by Neisser (1967), and there has been some debate about specific definitions and subcomponents of EF constructs (Burgess, Alderman, Evans, Emslie, & Wilson, 1998; Goldman-Rakic, 1987). This study utilizes a model of EF proposed by Gioia and colleagues (Gioia, Isquith, Guy, & Kenworthy, 2000), which includes two broad EF domains reflecting various components of behavioral/emotional regulation and metacognitive problem-solving skills. Previous research into neuropsychological outcomes in pediatric BT survivors utilizing performance-based tests has documented deficits in attention, processing speed, problem-solving, and metacognitive functions such as WM and strategic planning (Conklin et al., 2012; de Ruiter, van Mourik, Schouten-van Meeteren, Grootenhuis, & Oosterlaan, 2012; Wolfe, Madan-Swain, & Kana, 2012). Executive function deficits among cancer survivors have been linked to negative long-term economic/occupational outcomes, poor emotional health, and worse overall quality of life (Ellenburg et al., 2009; Waber et al., 2006). In a large-scale study, Ness and colleagues (2008) reported that pediatric cancer survivors with EF impairment were less likely to finish high school or be employed, and were at increased risk for emotional difficulties. Performance-based measures are most prevalent in studies evaluating cognitive late effects of cancer treatment, while neuropsychological impairment within home, school, and community settings has received relatively less attention (Campbell, et al., 2007; Peterson et al., 2008). Evaluation of everyday functioning addresses the concept of ecological validity, which refers to the relationship between the patient’s performance on a set of neuropsychological tests and the patient’s behavior in a variety of real world settings (Sbordone, 1996). Although literature provides evidence that traditional paperpencil measures have reasonable ecological validity (Chaytor & Schmitter-Edgecombe, 2003) many qualities of traditional neuropsychological measures limit the amount of variance in everyday skills that can be accounted for, as they are structured tasks administered in a largely controlled context. Thus, measures of everyday functioning may be more sensitive to problems in daily life that are not fully evident in a formal assessment setting (Chevignard, Soo, Galvin, Catroppa, & Eren, 2012). Utilizing parent and teacher ratings of EF in pediatric BT survivors provides an opportunity to capture unique information about their functioning in naturalistic settings. There have been several studies of neuropsychological and behavioral outcomes in survivors of pediatric cancers using behavior rating scales. The most prominent example of such research is being done as part of the Childhood Cancer Survivorship
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Study (CCSS; Ellenburg et al., 2009), which concluded that survivors of CNS malignancy in childhood are at significant risk for impairment in neurocognitive functioning in adulthood, especially if they have received cranial radiation, had a VP shunt placed, or suffered a cerebrovascular incident. Several studies have used the Behavior Rating Inventory of Executive Functioning (BRIEF; Gioia et al., 2000) specifically to examine EF in pediatric cancer survivors (Howarth et al., 2013; Kadan-Lottick et al., 2010; Wolfe et al., 2012). Results from these studies highlighted the presence of various areas of EF disruption in survivors of pediatric cancers, with particular risks associated with radiation treatment, age at diagnosis, age at the time of assessment, intellectual functioning, female gender, hearing impairment, and socioeconomic status (Howarth et al., 2013; Kadan-Lottick et al., 2010). Particular differences in EF between cancer survivors and non-affected comparison groups (i.e., sibling and non-CNS solid tumors) were documented in the areas of working memory (Howarth et al., 2013), task efficiency, memory, and emotional regulation (Kadan-Lottick et al., 2010). Research has also demonstrated the importance of EF in social functioning in survivors of pediatric brain tumors (Wolfe et al., 2012). To our knowledge, only one study to date has compared ratings from parents and teachers in this population of children, specifically related to response to methylphenidate treatment, and the results indicated only modest agreement between raters (Nelson et al., 2010). Our primary aim was to compare EF in childhood cancer survivors compared to same-aged healthy children (HC) by parent and teacher ratings on the Behavior Rating Inventory of Executive Function (BRIEF). As previous research shows EF deficits following treatment of pediatric CNS cancers (De Luca, Conroy, McCarthy, Anderson, & Ashley, 2009), we hypothesized that pediatric BT survivors would demonstrate higher mean parent and teacher ratings of executive dysfunction compared to HC. We also predicted a higher frequency of clinically elevated symptoms in the BT group compared to HC. Finally, we predicted that teacher ratings would reflect greater executive dysfunction in BT survivors compared to parent ratings, as the academic environment is often inherently more demanding on the EF system (Hartman, Rhee, Willcutt, & Pennington, 2007; Mares, McLuckie, Schwartz, & Saini, 2007).
METHOD All data included in this manuscript were obtained in compliance with the regulations of our institution and approved by the Institutional Review Board. Participants and procedures This is a retrospective, cross-sectional study of 62 pediatric BT survivors evaluated in our clinic between 2002 and 2013 (mean age = 12.02; SD = 3.56) and 62 age- and gender-matched HC (mean age = 11.79; SD = 3.21). Participant disease and treatment characteristics of the BT group were obtained via review of available medical records (Table 1). The BT and HC samples were nearly equal in gender representation (BT male = 30, 48.6%; female = 32, 51.6%; HC male = 31, 50%; female = 31; one BT/HC pair could not be matched on gender). BT survivors were included in the study if they were age 6 to 18 at assessment, had undergone chemotherapy and/or radiation
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G. C. WOCHOS ET AL. Table 1. Diagnostic characteristics of brain tumor sample Disease/treatment characteristics (N = 62)
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Age at diagnosis
Time since treatment Tumor type Medulloblastoma Ependymoma Astrocytoma Glioma Germinoma Craniopharyngioma Other tumor types Tumor recurrence* Yes No Treatment type Surgery + Chemotherapy + Radiation Chemotherapy Only Radiation Only Chemo+ Radiation Surgery+ Chemotherapy Surgery + Radiation Hydrocephalus* Yes No Seizures* Yes No Cerebellar Mutism* Yes No
Mean (SD) Range 5.81 (3.94) 1–14 years 4.68 (3.72) 0.30–15 years Frequency (%) 18 (29.0) 10 (16.1) 9 (15.5) 7 (11.3) 7 (11.3) 2 (3.2) 9 (14.5) 23 (37.1) 39 (62.9) 31 (50) 5 (8.1) 5 (8.1) 7 (11.3) 7 (11.3) 7 (11.3) 16 (25.8) 46 (74.2) 8 (12.9) 54 (87.1) 5 (8.1) 57 (91.9)
*Characteristics were historical, not present at the time of neuropsychological assessment.
treatment, and were off treatment and in remission/with stable disease. A total of 35 potential participants were excluded for not meeting inclusion criteria. Following completion of their treatment, each participant was clinically referred by their treatment team for a comprehensive neuropsychological assessment within the Division of Neuropsychology. Each neuropsychological assessment included parent and teacher-reported questionnaires of EF (BRIEF; Gioia et al., 2000). Of the 62 BT participants with a parent BRIEF, 50 also had a teacher BRIEF. Participants in the HC comparison group were selected from the original BRIEF normative sample and recruited from urban, sub-urban, and rural Maryland private and public schools, reflecting 1999 U.S. Census estimates for socioeconomic status, ethnicity, and gender distribution. Participants were excluded from inclusion in the normative sample if they had any history of learning (special education) or psychiatric impairment
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(prescribed psychotropic medication; Gioia et al., 2000). A recent meta-analysis demonstrated geographic equipoise (national and international), addressing recent concerns about heightened sensitivity of the BRIEF associated with sampling of the original standardization sample (Roth, Erdodi, McCulloch, & Isquith, 2014).
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Instruments and measures The BRIEF is a standardized questionnaire assessing EF by rating a child’s everyday behavior (Gioia et al., 2000). The BRIEF consists of 86 questions that contribute to eight EF domains comprising two indices: Behavioral Regulation and Metacognition. BRIEF domains and associated scale descriptions are presented in Table 2. Higher scores indicate greater impairment, with t-scores ≥ 65 indicating clinically significant symptomatology. Validity and test–retest reliability are well established (r = .82 for parents and .88 for teachers) with moderate correlations between teacher and parent ratings (r = .32–.34; Gioia et al., 2000). The BRIEF has been shown to demonstrate sensitivity to executive dysfunction in children with various developmental and acquired neurological disorders (Mautz et al., 2002). Data analysis Prior to data analysis, validity scales were checked for elevations (e.g., Negativity and Inconsistency scales) with no significant elevations identified in the sample. A profile analysis was conducted as mixed repeated-measures MANOVA to examine group Table 2. Description of BRIEF scales Scale
Behavioral description
Behavioral regulation Inhibit
Impulse control; ability to inhibit behaviors when necessary
Shift
Flexibility; mental flexibility in problem-solving; moving easily between situations, activities, or problems as needed
Emotional Control Metacognitive Initiate
Ability to modulate emotional responses appropriately
Working Memory
Ability to hold information in mind in order to complete a task and/or stay with an activity
Plan/Organize
Planning and organizational skills; Ability to anticipate future events, set goals; strategically plan and organize steps to complete tasks; understand and communicate key information
Organization of Materials
Ability to keep materials and environment orderly
Monitor
Self-monitoring; Ability to check and assess performance toward a goal; awareness of effects of one’s own behavior on others
Self-starting; Independently initiate tasks or activities; independently generate ideas
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differences across executive function domains. Scores on the eight BRIEF subscales served as within-participants variables, while group assignment (BT v. HC) served as the between-participants variable. We ran separate MANOVAs for Parent and Teacher BRIEF ratings. The Greenhouse-Geisser statistic was used in all analyses to control for violation of the sphericity assumption. To examine rater differences in the BT group, a repeated-measures MANOVA with two within-participants factors (rater and BRIEF subscales) was applied. Post-hoc paired-samples t-tests were run on those BRIEF subscales that were statistically significant in the MANOVA. Dichotomous variables were created to analyze clinically significant impairments. Each subscale was coded as: T ≤ 64 = 0, and T ≥ 65 = 1. Chi square was conducted to examine the frequencies of clinical elevations in each group (BT vs. HC) across BRIEF scales, and odds ratios (OR) were derived. In order to evaluate the frequencies of clinical elevations in the BT group between raters (parent vs. teacher), McNamar statistics were used. Finally, Pearson bivariate correlations were run to explore relationships between BRIEF scores with disease and treatment factors previously shown to be associated with neuropsychological impairment. Probability value was set at p < .05 for all analyses. We used Ferguson’s (2009) “recommended minimum effect size representing a ‘practically’ significant effect for social science data” (RMPE; Ferguson, 2009, p. 533), which suggests .04 for squared association indices (e.g., Eta-squared) and 2.0 for risk estimates (e.g., OR). We also applied Ferguson’s odds ratio effect size interpretations of moderate (OR ≥ 3.0) and strong (OR ≥ 4.0), when appropriate.
RESULTS Parent profile analysis Parent-rated EF did not reveal a statistically significant main effect for group or EF scale. However, there was a statistically significant group × EF interaction, F(4.93) = 3.12, p = .009, Eta2 = .025. Working memory (WM) was the only domain rated by parents as significantly higher in the BT group compared to the HC group, F(1) = 7.79, p = .006, Eta2 = .06, although the mean score is within the normal range for age (Figure 1). Further, examining the relationship between clinically elevated symptom levels (T ≥ 65) and group on parent rating indicated statistically significant differences on the Shift scale (χ2 = 4.21, p = .04), for which 16.1% of the BT survivors were clinically elevated (Figure 2). Parents of BT survivors were nearly four times more likely to report clinically significant inflexibility compared to parents of HCs (Table 3). Teacher profile analysis Teacher-rated EF revealed a significant main effect for group, F(1) = 14.51, p = .000, Eta2 = .117, and a significant group × EF interaction, F(3.53) = 4.19, p = .004, Eta2 = .037. The main effect for EF was not statistically significant, F(3.53) = 4.19, p = .173 Eta2 = .015. Mean teacher ratings in the BT group were significantly higher (i.e., greater impairment) than those for the HC comparison group in seven of the eight
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Figure 1. Mean scores on the BRIEF by parent and teacher reports for the brain tumor and healthy control groups.
Figure 2. Frequency of clinical elevations on scales of the BRIEF by group and rater.
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Table 3. Differences in proportions of the clinically elevated symptoms by group and rater
Parent profile analysis (brain tumor v healthy controls) (N = 62) Inhibit Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor Teacher profile analysis (brain tumor v healthy controls) (N = 50) Inhibit* Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor Rater profile analysis (parent v teacher) (N = 50)** Inhibit Shift Emotional Control Initiate Working Memory Plan/Organize Organization of Materials Monitor
Statistic (chi square)
Sign. (p)
Odds ratio (T ≥ 65)
95% confidence interval
.00 4.21 .90 .32 1.86 .89 1.97 .00
1.00 .04 .34 .57 .17 .34 .16 1.00
1.00 3.78 1.85 0.72 1.88 1.63 2.38 1.00
0.27–3.64 0.99–14.49 0.51–6.66 0.24–2.22 0.75–4.69 0.59–4.54 0.69–8.18 0.33–3.04
0.48 7.28 4.98 15.08 19.78 11.08 3.11 1.65
.49 .01 .03 .00 .00 .00 .06 .20
1.55 3.70 3.41 6.52 10.32 4.82 2.37 1.83
0.45–5.43 1.38–9.91 1.11–10.48 2.37–17.95 3.24–32.88 1.82–12.73 0.89–6.29 0.72–4.61
0.80 3.06 4.90 12.19 4.92 7.56 4.92 4.92
.38 .08 .02 .00 .02 .00 .02 .02
21.50 2.50 12.33 1.42 12.27 5.18 3.18 3.18
1.58–292.38 0.54–11.65 1.14–132.94 0.18–10.99 2.31–65.34 0.89–30.09 0.40–25.31 0.40–25.31
*Fisher Test Statistic was used because the minimum expected cell count requirement was not met. **McNemar NPAR statistic.
domains (Shift, Emotional Control, Initiate, WM, P/O, Organization of Materials, and Monitor), with effect sizes ranging from .01 to .21 (Figure 1). The relationship between clinically elevated symptoms (T ≥ 65) and group on teacher rating revealed statistically significant differences on five of the BRIEF scales including Shift (26% clinically elevated), Emotional Control (19%), Initiate (34%), WM (34%), and P/O (31%; Figure 2). Moderate to strong odds ratios emerged across these scales (Table 3). Rater profile analysis (BT only) As inter-rater reliability has been shown to be lower between parents and teachers (Achenbach, McConaughy, & Howell, 1987) and the normative sample for the BRIEF reported only modest correlations between parent and teacher ratings (Global Executive Composite [GEC], r = .340; Gioia et al., 2000), we examined the correlations within our sample and found greater consistency between parent and teacher ratings than
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reported for the normative sample (GEC r = .572; Metacogniton Index [MCI] r = .570; Behavior Regulation Index [BRI] r = .589). Intraclass correlations, however, did not meet minimum standards of agreement (ICC GEC r = .581). Comparing EF ratings from parents and teachers in the BT group revealed a significant main effect for rater (parent versus teacher); F(1, 49) = 21.57, p = .000, Eta2 = .306. There was also a significant main effect for EF, F(7, 48) = 7.84, p = .000, Eta2 = .561, but no significant rater by EF interaction effect (Figure 1). There were statistically significant differences across all eight EF domains such that teacher ratings were significantly higher than parent ratings for BT survivors (Table 4). All eight scale differences were modest, but met Ferguson’s (2009) RMPE odds ratio criteria. McNemar analyses of reported clinical elevations in the BT group by parents and teachers revealed statistically significant rater differences on six of the eight BRIEF scales (EC, Initiate, WM, P/O, Organization of Material, and Monitor). Effect sizes ranged from weak to strong (OR 1.42–12.33), and 95% Confidence Intervals suggest that this is likely driven by a few very impaired children (Table 3), which is consistent with the fact that overall mean scores in the BT group do not reach a level of clinical significance. Disease and treatment-related factors potentially associated with EF in the BT group were also examined. Clinically elevated EF was not found to be associated with age at diagnosis, tumor location, or a history of hydrocephalus, seizures, or cerebellar mutism syndrome. Elevated ratings on the P/O scale were significantly associated with the age at time of testing (r2 = .213, p = .048) and the time since treatment (r2 = .353, p = .005) by parents only. Elevations on the EC scale were significantly associated with having radiation therapy, again by parents only (r2 = .235, p = .033). Statistically significant relationships from teacher ratings were found with tumor recurrence and Table 4. Rater comparison in brain tumor group Parent (N = 62)
Teacher (N = 50)
Statistic (t)
Sign. (p)
Effect size (Cohen’s d)
M (SD)
Range
M (SD)
Range
Initiate
48.31 (9.69)
37–84
52.02 (9.52)
42–81
–3.27
.002
.47
Shift
52.55 (13.85)
36–92
59.52 (18.58)
42–111
–2.93
.005
.45
Emotional Control
49.74 (11.61)
36–83
56.28 (14.59)
44–101
–4.69
.000
.60
Initiate
51.68 (10.08)
35–83
58.80 (13.43)
41–81
–3.98
.000
.64
Working Memory
55.71 (11.14)
38–87
62.06 (16.54)
38–106
–3.21
.002
.46
Plan/Organize
53.63 (11.25)
37–84
60.30 (14.92)
42–104
–4.12
.000
.55
Organization of Materials
50.23 (10.95)
33–73
60.36 (21.81)
42–129
–3.48
.001
.62
Monitor
52.23 (12.34)
31–93
57.82 (14.57)
40–102
–2.99
.004
.51
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treatment with intrathecal chemotherapy. Specifically, clinical elevations on the Initiate (r2 = .375, p = .004), WM (r2 = .290, p = .020), P/O (r2 = .271, p = .028), and Monitor (r2 = .315, p = .013) scales were associated with the presence of tumor recurrence. Treatment with intrathecal chemotherapy was significantly related to elevations on the Shift (r2 = .282, p = .048), EC (r2 = .350, p = .018), and Organization of Materials (r2 = .302, p = .037) scales. Chi square analysis of the significant correlations above did not support a significant relationship on parent report between impaired planning and organization with age at testing or the amount of time since treatment completion. Nor was a significant relationship demonstrated between parent ratings of emotional dysregulation and radiation therapy. Significant bivariate correlations between teacher rated impairments with flexibility and organizing materials was not confirmed with chi square analysis. However, statistically significant relationships between tumor recurrence and teacher rated clinical impairments in initiation (Initiate 67% elevated; χ2 = 7.03, p = .008, Eta2 = .375), working memory (61% elevated; χ2 = 4.22, p = .040, Eta2 = .290), and self-monitoring (Monitor 44% elevated; χ2 = 4.97, p = .026, Eta2 = .315) were found.
DISCUSSION We aimed to compare EF in BT survivors and typically developing peers in their naturalistic settings (e.g., home and school). Consistent with previous literature, our results demonstrated that BT survivors exhibit various EF late effects, although these deficits appear to be most functionally disruptive in the formal learning environment (i.e., teacher ratings). Parents indicated WM to be the domain that significantly differed between survivors and their healthy peers, similar to the recent findings by Howarth and colleagues (2013). While as a group they did not exhibit clinically significant impairments in WM, nearly a quarter (24%) of the sample showed clinical impairment. Parents indicated a higher rate of clinically elevated problems associated with flexibility in the survivors, nearly four times that of typically developing children. Flexibility and WM limitations have been demonstrated in survivors previously (Maddrey et al., 2005; Palmer et al., 2003; Reddick et al., 2003; Ris et al., 2001; Robinson et al., 2013; Spiegler et al., 2004), as have other higher-order cognitive problems, although those did not emerge in our parent ratings. Teacher ratings, however, indicated more global and intense EF problems in a proportion of BT survivors than parent ratings. Nearly all areas of EF were significantly higher in BT survivors compared to HC, although again, average levels of the group as a whole were not significantly elevated. However, survivors were more likely to exhibit poor WM, problems with initiation, flexibility, and planning and organizational skills. Rates of functionally impairing difficulties in these areas ranged from three to more than ten times that of typically developing peers, with 26–34% exhibiting clinically significant problems. Similar inter-rater discrepancies have been documented in other pediatric clinical populations as well, including children with Attention-Deficit/ Hyperactivity Disorder (ADHD; Mares et al., 2007) and intellectual disability (Deb, Dhaliwal, & Roy, 2008; Nelson et al., 2010), highlighting the need for multimodal assessment. However, the pattern of inter-rater differences observed in our sample directly contrasts with previous findings reported in the BRIEF normative sample, as
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well as previous literature comparing parent and teacher ratings, which shows that parents consistently rate significantly greater EF difficulties than teachers (Gioia et al., 2000; Offord et al., 1996). Working memory and flexibility appear to be particularly vulnerable functional areas for disruption in some pediatric BT survivors. Teachers alone highlight significant problems with survivors’ ability to independently initiate tasks in a strategic and organized manner, and that insight into their difficulties and an ability to adjust their approach and develop novel strategies is also limited. These may be skills that are more in demand within the learning environment than in the home or social settings. The school environment places high demands on the executive system, as students are required to engage and sustain attention for extended periods of time, manage and manipulate novel information, develop solutions to various problems, and demonstrate their knowledge efficiently and effectively, with increasing independence over time. Differences in environmental demand and expectations are but one explanation for the discrepancy between parent and teacher ratings. Alternatively, parents of survivors may naturally adjust to their child’s needs and provide a higher, more individualized level of support around EF difficulties, diminishing how functionally disruptive such problems are in the home setting. Altered (diminished) expectations by parents following diagnosis and treatment of a brain tumor in one’s child may also contribute to these observed differences. For example, several studies have identified response bias and a tendency to minimize negative mood symptoms and deny quality of life difficulties on self-report measures among adolescent and adult cancer survivors (Bauld, Anderson, & Arnold, 1998; Canning, Canning, & Boyce, 1992; O’Leary, Diller, & Recklitis, 2007). Such findings are consistent with social desirability theory, whereby cancer survivors, by means of adaptive self-preservation following their cancer experience, emphasize positive personal traits and minimize negative symptoms. Shelder, Mayman, and Manis (1993) also argue that a positive illusory bias may be a psychosocial risk-factor for survivors of various medical illnesses. Similarly, Sprangers and Schwartz (1999) described a phenomenon of response shift in the assessment of quality of life outcomes, in which patients confronted with a life-threatening illness change or “recalibrate” their internal standards of measurement with regard to quality of life on self-report measures. This might also apply to parent’s standards for evaluating their child’s functioning in response to the diagnosis and treatment of such a significant medical event, potentially explaining the minimal symptoms of executive dysfunction endorsed by parents compared to teachers. This study is, to our knowledge, the first to compare everyday EF in pediatric BT survivors to typically developing peers across multiple environments and raters. This cross-validation of EF between different respondents provides a more comprehensive view of a child’s real-world functioning, and assesses a broad range of dynamic EF skills in different contexts using a single instrument. Our results highlight an important practical matter—that utilization of a single instrument from a single rater to determine neuropsychological functioning might not be adequate in this particular patient population—even as a screening tool to help identify alterations in neuropsychological functioning over time. In addition, while previous studies have reported an unexpected response bias/shift on self-report measures in cancer survivors, our findings raise similar concerns regarding parent report in younger survivors. These findings highlight a need for further research in this area.
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Our examination of disease and treatment-related factors that may relate to EF impairment in BT survivors produced mixed results. Previous literature indicates that factors associated with poorer neuropsychological outcomes in this population include tumor location (Mulhern, Hancock, Fairclaugh, & Kun, 1992), age at diagnosis (Sands et al., 2001) and radiation treatment (Reamers et al., 2003). Our results indicate that there might be an association between tumor recurrence, treatment with radiation and/or intrathecal chemotherapy, the time since completion of treatment, and the age of the child when evaluated and greater risk of some EF impairments. However, only tumor recurrence was associated with a higher proportion of survivors being rated by teachers as having clinically significant impairments in working memory, self-starting, and selfawareness. The lack of expected convergence with prior literature might have to do with the fact that the majority of prior research has been based on performance-based measures of EF in the lab setting, while this study focused on ratings of real-world EF across multiple environments within which survivors are engaged. Several limitations and considerations for future research bear mention. Interpretation of the findings of this study must consider the limitations inherent to retrospective, cross-sectional research. The participants were clinically referred, resulting in the possibility of sample bias toward a more impaired sample. In addition, the BT sample itself was heterogeneous with regard to disease and treatment characteristics (e.g., tumor and treatment type), disease/treatment complications (e.g., tumor recurrence, presence of cerebellar mutism, hydrocephalus, or seizures), and disease/treatment specific demographic variables (e.g., age at diagnosis and treatment, time since treatment). This complicates the ability to generalize to the pediatric BT population more globally, although we did examine these variables, which allowed some characterization of the sample of EF-impaired children. Additional limits to generalizability include our inability to match participants on socio-economic status or global cognitive abilities (e.g., intelligence), the absence of additional BT sample demographic variables that might influence parent ratings (e.g., parent education level and employment status, special education status, grade retention), the use of a single behavior rating scale, as well as the inherent flaws associated with rating scales (e.g., relying on a third party for ratings of a child’s behavior, potential for rater bias as previously discussed above). Nonetheless, our results further support the importance of individualized neuropsychological assessment and cross validation of EF measures in BT survivors following treatment, as at least a subset of survivors exhibit disruptions in typical EF development that impacts their daily functioning.
REFERENCES Achenbach, T., McConaughy, S., & Howell, C. (1987). Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity. Psychological Bulletin, 101, 213–232. Bauld, C., Anderson, V., & Arnold, J. (1998). Psychosocial aspects of adolescent cancer survival. Journal of Pediatrics and Child Health, 34, 120–126. Burgess, P. W., Alderman, N., Evans, J., Emslie, H., & Wilson, B. A. (1998). The ecological validity of tests of executive function. Journal of the International Neuropsychological Society, 4, 547–558.
Downloaded by [University of California, San Diego] at 23:58 11 January 2015
EXECUTIVE DYSFUNCTION IN BRAIN TUMOR SURVIVORS
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Campbell, L. K., Scaduto, M., Sharp, W., Dufton, L., Van Slyke, D., & Compas, B. (2007). A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatric Blood and Cancer, 49, 65–73. Canning, E. H., Canning, R. D., & Boyce, W. T. (1992). Depressive symptoms and adaptive style in children with cancer. Journal of the American Academy of Child and Adolescent Psychiatry, 31, 1120–1124. Chevignard, M. P., Soo, C., Galvin, J., Catroppa, C., & Eren, S. (2012). Ecological assessment of cognitive functions in children with acquired brain injury: A systemic review. Brain Injury, 26, 1033–1057. doi:10.3109/02699052.2012.666366 Chaytor, N., & Schmitter-Edgecombe, M. (2003). The ecological validity of everyday neuropsychological tests: A review of the literature on everyday cognitive skills. Neurospychology Review, 13, 191–197. doi:10.1023/B:NERV.0000009483.91468.fb Conklin, H. M., Ashford, J. M., Howath, R. A., Merchant, T. E., Ogg, R. J., Santana, V. M., . . . Xiong, X. (2012). Working memory performance among childhood brain tumor survivors. Journal of the International Neuropsychological Society, 18, 996–1005. Deb, S., Dhaliwal, A. J., & Roy, M. (2008). The usefulness of conners’ rating scales-revised in screening for attention deficit hyperactivity disorder in children with intellectual disabilities and borderline intelligence. Journal of Intellectual Disability Research, 52, 950–965. De Luca, C. R., Conroy, R., McCarthy, M. C., Anderson, V. A., & Ashley, D. M. (2009). Neuropsychological impact of treatment with brain tumors. Cancer Treatment Resources, 150, 277–296. doi:10.1007/b109924_17 de Ruiter, M. A., van Mourik, R. V., Schouten-van Meeteren, A. Y. N., Grootenhuis, M. A., & Osterlaan, J. O. (2012). Neurocognitive consequences of a pediatric brain tumour and its treatment: A meta-analysis. Developmental Medicine & Child Neurology, 55, 408–417. Ellenberg, E., Liu, Q., Gioia, G., Yasui, Y., Packer, R. J., Mertens, A., . . . Zeltzer, L. K. (2009). Neurocognitive status in long-term survivors of CNS malignancies: A report from the childhood cancer survivor study. Neuropsychology, 23, 705–717. doi:10.1037/a0016674 Ferguson, C. J. (2009). An effect size primer: A guide for clinicians and researchers. Professional Psychology: Research and Practice, 40, 532–538. Gioia, G. A., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000). Behavior rating inventory of executive function. Odessa, FL: Psychological Assessment Resources. Gioia, G. A., Isquith, P. K., Kenworthy, L., & Barton, (2002). Profiles of everyday executive function in acquired and developmental disorders. Child Neuropsychology, 8, 121–137. Goldman-Rakic, P. (1987). Circuitry of primate pre-frontal cortex and regulation of behavior by representational memory. In F. Plum (Ed.), Handbook of physiology: The nervous system (pp. 373–417). New York, NY: Oxford University Press. Hartman, C. A., Rhee, S. H., Willcutt, E. G., & Pennington, B. F. (2007). Modeling rater agreement for ADHD: Are parents or teachers biased? Journal of Abnormal Child Psychology, 35, 536–542. Howarth, R. A., Ashford, J. M., Merchant, T. E., Ogg, R. J., Santana, V., Shengjie, W., . . . Conklin, H. M. (2013). The utility of parent report in assessment of working memory among child brain tumor survivors. Journal of the International Neuropsychological Society, 19, 380–389. doi:10.1017/S1355617712001567 Jain, N., Browers, P., Okcu, M. F., Cirino, P. T., & Krull, K. R. (2009). Sex specific attention problems in long-term survivors of pediatric acute lymphoblastic leukemia. Cancer, 115, 4238–45. Kaatsch, P. (2010). Epidemiology of childhood cancer. Cancer Treatment Reviews, 36, 277–285. doi:10.1016/j.ctrv.2010.02.003 Kadan-Lottick, N. S., Zeltzer, L. K., Lui, Q., Yasui, Y., Ellenberg, L., & Gioia, G., . . . Krull, K. R. (2010). Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers. Journal of the National Cancer Institute, 102, 881–893. doi:10.1093/jcni/ djq156
Downloaded by [University of California, San Diego] at 23:58 11 January 2015
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Krappmann, P., Paulides, M., Stohr, W., Ittner, E., Plattig, P., & Nickel, P.,... Langer, T. (2007). Almost normal cognitive function in patients during therapy for childhood acute lymphoblastic leukemia without cranial irradiation according to ALL-BFM 95 and COALL 06-97 protocols: Results of an Austrian-German multicenter longitudinal study and implications for follow-up. Pediatric Hematology and Oncology, 24, 101–109. Lezak, M. D., Howieson, D. B., & Loring, D. W. (2004). Neuropsychological assessment (4th ed.). New York, NY: Oxford University Press. Macedoni-Luksic, M., Jereb, B., & Todorovski, L. (2003). Long-term sequelae in children treated for brain tumors: Impairments, disability, and handicap. Pediatric Hematology. Oncology, 20, 89–101. Maddrey, A. M., Bergeron, J. A., Lombardo, E. R., McDonald, N. K., Mulne, A. F., Barenburg, P. D., & Bower, D. C. (2005). Neuropsychological performance and quality of life of 10 year survivors of childhood medulloblastoma. Journal of Neurooncology, 72, 245–253. doi:10.1007/s11060-004-3009-z Mares, D., McLuckie, A., Schwartz, M., & Saini, M. (2007). Executive function impairments in children with attention-deficit hyperactivity disorder: Do they differ between school and home environments? Canadian Journal of Psychiatry, 52, 527–534. Mautz, W., Carpentieri, S., Shapiro, B., Dalton, V., Gelber, R., Sallan, S., et al. (2002). Absence of progression of cognitive sequelae 4 to 7 years after CRT for ALL [Abstract]. Journal of the International Neuropsychological Society, 8, 292. Merchant, T. E., Kiehna, E. N., Miles, M. A., Zhu, J., Xiong, X., & Mulhern, R. K. (2002). Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors. International Journal of Radiation Oncology Biology Physics, 53, 1271–1278. Mulhern, R. K., Hancock, J., Fairclaugh, D., & Kun, L. (1992). Neuropsychological status of children treated for brain tumors: A critical review and integrative analysis. Medical and Pediatric Oncology, 20, 181–191. Mulhern, R. K., Palmer, S. L., Reddick, W. E., Glass, J. O., Kun, L. E., & Taylor, J., . . . Gajjar, A. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. Journal of Clinical Oncology, 19, 472–479. Neisser, U. (1967). Cognitive psychology. New York, NY: Appleton-Century-Crofts. Ness, K. K., Gurney, J. G., Zeltzer, L. K., Leisering, W., Mulrooney, D. A., Nathan, P. C., … Mertens, A. C. (2008). The impacts of limitations on physical, executive, and emotional function on health-related quality of life among adult survivors of childhood cancer: A report for the childhood cancer survivor study. Archives of Physical Medicine and Rehabilitation, 89, 128–136. Nelson, K. L., Conklin, H. M., Ashford, J. M., Kahalley, L. S., Wu, S., & Xiong, X. (2010). Parent and teacher ratings of attention during a year-long methylphenidate trial in children treated for cancer. Journal of Pediatric Psychology, 26, 438–450. Offord, D. R., Boyle, M. H., Racine, Y., Szatmari, P., Fleming, J. E., Sanford, M., & Lipman, E. L. (1996). Integrated assessment data from multiple informants. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1078–1085. O’Leary, T. E., Diller, L., & Recklitis, C. J. (2007). The effects of response bias on self-reported quality of life among childhood cancer survivors. Quality of Life, 16, 1211–1220. Palmer, S. L., Gajjar, A., Reddick, W. E., Glass, J. O., Kun, L. E., & Wu, S. (2003). Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology, 17, 548–555. doi:10.1037/ 0894-4105.17.4.548 Peterson, C. C., Johnson, C. E., Ramirez, J. Y., Huestis, S., Pai, A. L., Demaree, H. A., & Drotar, D. (2008). A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia. Pediatric Blood Cancer, 51, 9–104.
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Porter, K. R., McCarthy, B. J., Freels, S., Kim, Y., & Davis, F. G. (2010). Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology. Neuro Oncology, 12, 520–527. doi:10.1093/neuonc/nop066 Reamers, T. S., Ehrenfels, S., Mortensen, E. L., Schmiegelow, M., Sonderkaer, S., Carstensen, H., … Muller, J. (2003). Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors. Medical and Pediatric Oncology, 40, 26–34. Reddick, W. E., White, H. A., Glass, J. O., Wheeler, G. C., Thompson, S. J., & Gajjar, A., . . . Mulhern, R. K. (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric deficits in pediatric brain tumor survivors. Cancer, 15, 2512–2519. doi:10.1002/cncr.11355 Ris, D. M., Packer, R., Goldwein, J., Jones-Wallace, D., & Boyett, J. M. (2001). Intellectual outcome after reduced dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: A Children’s Cancer Group study. Journal of Clinical Oncology, 19, 3470–3476. Robinson, K. E., Fraley, C. E., Pearson, M. M., Kuttesch, J. F., & Compas, B. E. (2013). Neurocognitive late effects of pediatric brain tumors of the posterior fossa: A quantitative review. Journal of the International Society of Neuropsychology, 19, 44–53. doi:10.1017/ S135561712000987 Roth, R. M., Erdodi, L. A., McCulloch, L. J., & Isquith, P. K. (2014). Much ado about norming: The Behavior Rating Inventory of Executive Function. Child Neuropsychology. [Epub ahead of print] PubMed PMID: 24650292. Sands, S. A., Kellie, S. J., Davidow, A. L., Diez, B., Villablanca, J., Weiner, H. I., … Finlay, J. L. (2001). Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: From the First International CNS Germ-Cell Tumor Study. Neuro-Oncology, 3, 175–183. Sbordone, R. J. (1996). Ecological validity: Some critical issues for the neuropsychologist. In R. J. Sbordone & C. J. Long (Eds.), Ecological validity of neuropsychological testing (pp. 15–41). Delray Beach, FL: GR Press/St. Lucie Press. Shelder, J., Mayman, M., & Manis, M. (1993). The illusion of mental health. The American Psychologist, 48, 1117–1131. Spiegler, B. J., Boufett, E., Greenberg, M. L., Rutka, J. T., & Mabbott, D. J. (2004). Change in neurocognitive functioning after treatment with cranial radiation in childhood. Journal of Clinical Oncology, 22, 706–713. doi:10.1200/JCO.2004.05.186 Sprangers, M. A. G., & Schwartz, C. E. (1999). Integrating response shift into health-related quality of life research: A theoretical model. Social Science & Medicine, 48, 1507–1515. Waber, D. P., Pomeroy, S. L., Chiverton, A. M., Kieran, M. W., Scott, R. M., Goumnerova, L. C., & Rivkin, M. J. (2006). Everyday cognitive function after craniopharyngioma in childhood. Pediatric Neurology, 34, 13–19. doi:10.1016/j.pediatrneurol.2005.06.002 Wolfe, K. R., Madan-Swain, A., & Kana, K. (2012). Executive dysfunction in pediatric posterior fossa tumor survivors: A systematic literature review of neurocognitive deficits and intervention. Developmental Neuropsychology, 37, 153–175. Wolfe, K. R., Walsh, K. S., Reynolds, N. C., Mitchell, F., Reddy, A. T., Paltin, I., & Madan-Swain, A. (2012). Executive functions and social skills in survivors of pediatric brain tumor. Child Neurosychology iFirst, 1–15, doi:10.1080/09297049.2012.669470
