Neuropsychological Late Effects Research Articles

Neuropsychological late effects and quality of life outcomes in pediatric brain tumor survivors: Role of pediatric neurologists in monitoring and management

Pediatric brain tumor (PBT) survivors are at significantly increased risk of cognitive, psychosocial, and educational/vocational sequelae that impact health related quality of life. These complications and health morbidities result in high burden on survivors and their families, particularly those already vulnerable to disparities in healthcare access and outcomes. Since neurological comorbidities are common in this population, neurologists are uniquely positioned to screen, treat identified symptoms, and connect families with services and resources. A tiered assessment approach can facilitate early identification of concerns and reduce barriers to care. We review common presenting conditions, highlight risk factors, and provide screening tools and recommendations to facilitate comprehensive survivorship care for PBT survivors.

31 Outcomes of an ACT-Based Group Protocol on Neuropsychological Late Effects in Survivors of Childhood Cancer

Objective:Attention of the research community on childhood cancer has grown exponentially over the last 5 decades (Robinson & Hudson, 2014). With research attention growing rapidly, cure rates have increased just as dramatically, with survivorship well over 80% (Ward, et al., 2014). With survivorship on the rise, research has turned to the examination of late effects in survivors of childhood cancer, especially neuropsychological late effects (Krull, et al., 2018). Late effects, functional impairment, and the awareness of one’s own impairment can create several lasting issues in a survivor’s life (Oeffinger, et al., 2010). The objective of this study is to explore the feasibility and functionality of a group intervention for this population.Participants and Methods:Participants were recruited from a pediatric cancer institute in southern California. To be considered for inclusion, participants must have completed curative treatment for childhood cancer, not be currently undergoing treatment for childhood cancer, be free of any severe and persistent mental illnesses, and have access to a stable internet connection (for Zoom sessions). This study examined the impact of an Acceptance and Commitment Therapy (ACT)-based group intervention protocol on survivors of childhood cancer. Specifically, this study explored a strategy to identify early neuropsychological late effects and a strategy to improve these impacts. The group intervention was conducted via Zoom (www.zoom.us) which provided an opportunity to continue to provide this service in the wake of COVID-19. Data was collected at baseline and at the completion of the group intervention. This data focused on the functional and perceived impacts of neuropsychological sequelae in these participants, as well as the changes as related to the group intervention.Results:Data did not show any significant changes from baseline to follow-up in this population. The lack of significance was likely due to a severely truncated sample size. Despite the lack of significant findings, data appears to trend negatively. Although these findings do not provide conclusive evidence for this ACT-based group as an intervention for neuropsychological late effects in survivors of childhood cancer, the data suggested some interesting trends which will be explored further in this presentation.Conclusions:The results of this study help to further explore the importance of attention to neuropsychological symptoms and issues in survivors of childhood cancer, especially within the first few years following the completion of treatment. As survivorship continues to increase, it will be of utmost importance to continue to examine the impact of neuropsychological late effects and how the field of neuropsychology can best serve this population. This study was severely limited by a small sample size, a single clinician providing the protocol, and a truncated timeline. Further research will examine the impact of this study protocol in a larger sample size, which will likely increase the ability to reject the null hypothesis. In addition, future research must also be conducted to better explore strategies of early and consistent neuropsychological intervention in this population.

3 Predicting Neuropsychological Late Effects in Pediatric Brain Tumor Survivors Using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity

Objective:Pediatric brain tumor survivors (PBTS) represent a growing group of childhood cancer survivors vulnerable to adverse neuropsychological outcomes following treatment. Although the identification of risk factors has motivated the efforts to reduce the incidence of neuropsychological late effects in PBTS, most of the prior research on late effects has examined these risk factors on an individually selective basis. Given that tumordirected treatments generally involve a multimodal approach, consisting of a combination of surgical resection, chemotherapy, and/or radiation, and that each patient may have varying degrees of neurological complications, research is needed that focuses on neurocognitive risk factors holistically. The Neurological Predictor Scale (NPS) measures neurological complications associated with neurocognitive risks (e.g., hydrocephalus) and the use of various tumordirected treatment modalities (e.g., craniospinal radiation). The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of pediatric brain tumor treatments, but its association with neuropsychological late effects has not been well-established. The present study aims to 1) evaluate treatment intensity as a risk factor for the development of neuropsychological late effects; and 2) expand upon the validity and clinical utility of the NPS and PNORTI as predictive measures for the development of neuropsychological late effects in PBTS.Participants and Methods:A retrospective chart review was completed of PBTS (n = 167, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment (surgery, chemotherapy, and/or radiation therapy) and without a multi-system genetic disorder or severe developmental delay prior to brain tumor diagnosis. Neuropsychological outcomes of interest (IQ, processing speed, working memory, verbal comprehension, and perceptual reasoning) were analyzed in relation to the NPS and PNORTI.Results:NPS scores ranged from 1 to 11 (M = 5.58, SD = 2.28) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). Survivors were on average approximately 6 years post-treatment (M = 6.13, SD = 3.39). Pearson bivariate correlations revealed that NPS scores were significantly correlated with IQ (r = -.20, p = .015) and processing speed (r = -.27, p = .015). Models examining the predictive utility of the NPS on neuropsychological outcomes showed that, when controlling for age at diagnosis and sex, NPS scores significantly predicted IQ [F(3, 147) = 10.83, p < .001, R2 = .18, R2adjusted = .16] and processing speed [F(3,88) = 5.62, p = .001, R2 = .16, R2adjusted = .13]. A one-way ANOVA showed no significant differences on neuropsychological outcomes based on PNORTI scores.Conclusions:The findings suggest that the NPS has value in predicting IQ and processing speed above and beyond demographic variables. However, treatment intensity (PNORTI) was not associated with neuropsychological domains in our sample. Future longitudinal research should examine which specific neurological risk factors within the NPS account for the most variance in neuropsychological outcomes.

14 The Impact of Socioeconomic Status (SES) on Phonemic Fluency in Patients with Pediatric Brain Tumor (PBT)

Objective:Phonemic fluency, an important cognitive skill for everyday functioning, has been shown to decline in comparison to same-aged peers following pediatric cancer diagnosis and treatment, despite intact semantic fluency. More generally, socioeconomic status (SES) has recently been shown to be one of the strongest predictors of neuropsychological outcomes among pediatric oncology patients, with lower SES predicting worse intellectual and academic functioning. However, the association between SES and phonemic fluency within this population has yet to be explored. The main objective of this project was to determine whether SES (specifically estimated household income) significantly predicts phonemic fluency performance among patients with PBT, and it was hypothesized that higher SES would be associated with better phonemic fluency outcomes.Participants and Methods:136 participants with PBT ages 7-20 (x=14.15 years, SD=3.87), were administered phonemic fluency trials (either from the NEPSY - Second Edition or Delis-Kaplan Executive Function System, with no significant differences in performance between measures). The sample was 58.8% male and half Latino (50.0%), followed by Caucasian (30.1%), Asian American (7.4%), Black (6.6%), and Other (5.9%) ethnicity. All patients identified English as their primary and preferred language regardless of predominant household language, reducing the potential confounding impact of language. Given documented associations between PBT and lower intelligence following diagnosis and treatment, estimated intellectual functioning was included in the first block of hierarchical regression to isolate and further elucidate the potential contributing influence of SES on phonemic fluency. Median household income for specific neighborhoods was used as a proxy for SES, while Wechsler Matrix Reasoning (MR) was used as an estimate of general intellectual functioning given the high correlation between MR and full scale IQ.Results:Consistent with prior literature, phonemic fluency was lower than normative age expectations [t(135)=-3.653, p=.0002], though still within the average range clinically (x=8.93). As hypothesized, SES was positively correlated with phonemic fluency [r(136)=.219, p=.005]. Furthermore, SES significantly predicted phonemic fluency performance above and beyond estimated intelligence, accounting for a significant increase in variance (p=.020). Post-hoc analyses also revealed poorer phonemic fluency among participants with infratentorial brain tumors as compared to supratentorial brain tumors after controlling for SES, t(108)=-1.748, p=.042.Conclusions:Consistent with the known impact of SES on neuropsychological late effects among patients with pediatric cancer, phonemic fluency was positively correlated with SES among participants with PBT above and beyond estimated intelligence, suggesting the distinct role of SES on rapid verbal retrieval within this population. This has important implications for identifying patients at higher risk, helping to ensure timely provision of services and supports. Poorer phonemic fluency was also noted among patients with infratentorial (vs. supratentorial) brain tumors after controlling for SES, which may influence studies combining tumor location as the vast majority of PBTs are infratentorial. This supports prior literature demonstrating the need for increased cerebellar activation during phonemic (vs. semantic) retrieval. Additional research is needed to further explore these findings.

Predicting neuropsychological late effects in pediatric brain tumor survivors using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity.

The Neurological Predictor Scale (NPS) quantifies cumulative exposure to tumor- and treatment-related neurological risks. The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of different treatment modalities, but research is needed to establish whether it is associated with late effects. This study evaluated the predictive validity of the NPS and PNORTI for neuropsychological outcomes in pediatric brain tumor survivors. A retrospective chart review was completed of pediatric brain tumor survivors (PBTS) (n = 161, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment. Attention, intellectual functioning, perceptual reasoning, processing speed, verbal reasoning, and working memory were analyzed in relation to the NPS and PNORTI. NPS scores ranged from 1 to 11 (M = 5.57, SD = 2.27) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). When controlling for age, sex, SES factors, and time since treatment, NPS scores significantly predicted intellectual functioning [F(7,149) = 12.86, p < .001, R2 = .38] and processing speed [F(7,84) = 5.28, p < .001, R2 = .31]. PNORTI scores did not significantly predict neuropsychological outcomes. The findings suggest that the NPS has value in predicting IF and processing speed above-and-beyond demographic variables. The PNORTI was not associated with neuropsychological outcomes. Future research should consider establishing clinical cutoff scores for the NPS to help determine which survivors are most at risk for neuropsychological late effects and warrant additional assessment.

INSP-06. Recent advances in improving neuropsychological outcomes for paediatric brain tumour patients - Are we entering a new era?

Children and youth treated for brain tumours can sustain a brain injury as a consequence of the tumour and curative therapy leaving them with significant cognitive challenges. Advances in treatment for paediatric brain tumours – particularly the delivery of radiotherapy – have been associated with improved neuropsychological outcome in survivors, however. This presentation will first focus on work documenting the impact of changes in cranial radiotherapy delivery and modality on neuropsychological late effects in children treated for medulloblastoma. Outcomes in patients treated on modern protocols are substantially improved relative to prior therapy, however challenges remain. Second, novel approaches for cognitive recovery and brain repair in survivors of paediatric brain tumours will be discussed, with a focus on novel approaches for fostering endogenous neuroplasticity for cognitive recovery and brain repair in children and youth treated for paediatric brain tumours.

QOL-29. Neuropsychology for you“ – tools to improve awareness of and access to neuropsychological care

OBJECTIVE: The occurrence of neuropsychological late effects in childhood brain tumor patients is well known in literature and practice, as well as the use of neuropsychological testing and therapy procedures. Despite guidelines, actual care is quite heterogeneous and often does not meet the needs due to lack of resources. Therefore, a standardized tool to improve awareness of and access to neuropsychological assessment, but even more treatment was developed. METHODS: The core of this Quality-Improvement project is a multilevel and interdisciplinary approach characterized by iterative processes (PDSA-cycles): (1) conceptualization by interdisciplinary, multicenter teams of experts, (2) consensus in Delphi surveys by medical, nursing and psychosocial experts (N=45) and final approval by the steering group. (3) Pilot phases (N=44): Manageability and acceptance, emotional well-being and the degree of information were recorded using a process-oriented screening. RESULTS: The expert meetings resulted in two booklets ("Look closely - Psychosocial assessment" & "1,2,3 - All about Neuropsychology"): Each booklet offers creative methods with a high prompting character to motivate the child to participate actively in two face-to-face sessions (psychoeducational, work and exercise and reflection section). They enable patients to make themselves experts on these topics with age-appropriate, interactive methods. The Delphi survey revealed a consensus of 69%-93%. Patients using the Psychosocial-assessment booklet showed generally low negative emotions and stable positive emotions, which significantly increased during the second session (Z = 2.156, p = .031). Moreover, positive emotions increase significantly during the second session (Z = 2.805, p = .005). Self-indicated degree of information increases significantly with both booklets (Psychosocial assessment: Z = 3.133, p = .002; Neuropsychology: Z = 2.751, p = .006). CONCLUSION: The results illustrate a positive emotional approach to neuropsychological assessment and treatment. Likewise, the rapid increase in expert knowledge supports access to this specific topic and can be considered a minimum standard.

Neuropsychological surveillance model for survivors of pediatric cancer: A descriptive report of methodology and feasibility

Objective: Neuropsychological late effects of pediatric cancer may not become apparent for years after therapy; therefore, serial monitoring is necessary for detecting changes to ensure timely intervention. Unfortunately, lack of access to neuropsychologists, increased patient volume, insurance authorization and reimbursement issues, time required for neuropsychological evaluation, and practice effects related to repeat testing present many challenges to provision of neuropsychological care for survivors of childhood cancer. Models involving surveillance and monitoring have been proposed, though minimal data exist related to the implementation and feasibility of such models. Method: In this descriptive feasibility study, the Neuropsychology Consult Clinic (NCC) at Children’s Hospital Los Angeles is presented, outlining a methodology and algorithm for neuropsychological surveillance of survivors of non-CNS pediatric cancer and an account of the first three years of clinic implementation. Participants included 215 survivors (x̅ age = 5.6 years), including 75.3% Latinx patients. Results: The overall clinic implementation was found to be feasible, with approximately 75% of patients “passing” the screening and 25% “failing” the screening. Clinical judgment only conflicted with the algorithm 8.6% of the time. However, several limitations to feasibility were noted, including validity concerns and ability/time to complete parent-reported outcomes using Spanish forms, as well as access to bilingual examiners. Conclusions: These preliminary data support the feasibility of the NCC model with limitations as outlined above. This is the first phase in a multiphase plan to develop an appropriate screening clinic for survivors of pediatric cancer, with the next phase focusing on sensitivity/specificity of measures.

Late effects of pediatric brain tumors.

Adverse late effects of pediatric brain tumors can be numerous and complex and potentially alter the life trajectories of survivors in a multitude of ways. We review these inter-related late effects that compromise neurocognitive function, general health, social and psychological adjustment, and overall adaptive and vocational outcomes, and threaten to undermine the ability of survivors to transition independently into adulthood and effectively manage their care. Intervention/prevention strategies and advances in treatment that may reduce such late effects are discussed. Studies of neuropsychological late effects have revealed specific deficits in core cognitive functions of attention, working memory and processing speed, with many survivors demonstrating decline in working memory and processing speed over time, irrespective of tumor type or treatment. This in turn affects the ongoing development of higher order neurocognitive skills. Research also highlights the increasing burden of health-related, neuropsychological and psychosocial late effects into adulthood and impact across life outcomes. Pediatric brain tumor survivors require coordinated interdisciplinary care, ongoing evaluation and management of late effects, and timely interventions focused on mitigating the impact of late effects. The transition to adulthood can be especially vulnerable and addressing barriers to care is of paramount importance.

Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy.

Little is known about cognition and predictors of neuropsychological outcomes in pediatric low-grade glioma (PLGG) survivors treated without radiation therapy. This research expands upon our previous work by further identifying the cognitive profile of PLGG patients treated without radiation therapy, investigating the specific medical and demographic variables that predict functioning, and examining white matter structure and its relationship to neuropsychological performance. Nineteen PLGG patients (11-19 years) were administered the Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale, and subtests from the Woodcock-Johnson Tests of Cognition (visual matching, rapid picture naming, and pair cancellation) and Cambridge Neuropsychological Test Automated Battery (pattern recognition memory, delayed matching to sample, intra-extra dimensional set shift, motor screening task, rapid visual information processing, and spatial span). The sample had normative weaknesses in verbal working memory, brief attention/vigilance, psychomotor speeded output, visual perception and matching, overall cognition, working memory, and processing speed. Increased surgeries or subtotal resections, hydrocephalus, shunting procedures, chemotherapy, NF1, and supratentorial location were predictive of cognitive deficits. Broad white matter involvement of the frontal, temporal, parietal, and occipital lobes as well as the cerebellum, as inferred from diffusion tensor imaging indices of decreased fiber orientation and increased water diffusion, was related to many cognitive difficulties. This study comprehensively examines cognitive functioning in PLGG patients treated without radiation therapy, predictors of cognition, and its relation to white matter structure. Our findings indicate that medical and demographic variables other than radiation therapy can lead to cognitive late effects with diffuse white matter involvement.

Predicting Neuropsychological Late Effects in Medulloblastoma With Post Radiation Hippocampal Volume

Predicting Neuropsychological Late Effects in Medulloblastoma With Post Radiation Hippocampal Volume

The potential utility of parent-reported attention screening in survivors of childhood cancer to identify those in need of comprehensive neuropsychological evaluation.

Survivors of childhood cancer are at risk for neuropsychological late effects, yet identifying those in need of evaluation and obtaining needed services can be challenging for the medical team. Finding time- and cost-effective screening measures that can be used to identify children in need of evaluation is a clinical priority. Our objective was to investigate the association between parent-rated attention problems and related neuropsychological impairments in childhood cancer survivors as a means of identifying those at high risk for difficulties. Cognitive and psychosocial data of survivors who completed neuropsychological evaluations were retrospectively abstracted. Parents of 70 survivors of pediatric cancer (mean age, 11.6 years) completed the Conners Parent Rating Scale and the Child Behavior Checklist. Children also completed a measure of intellectual functioning. The 18 symptoms of inattention and hyperactivity were abstracted from the Conners questionnaire, and participants were classified according to whether or not they met attention deficit/hyperactivity disorder (ADHD) symptom criteria (≥6 inattentive symptoms). Survivors who met symptom criteria for ADHD (27%) demonstrated greater impairments in IQ and working memory, but not processing speed, than survivors who did not. Meeting ADHD symptom criteria was also associated with greater externalizing and social problems but not more internalizing symptoms. ADHD symptom screening was associated with low sensitivity (range = 26.3%-69.2%) but stronger specificity (range = 75.0%-82.7%) for neuropsychological difficulties. Parental ratings of attentional symptoms may be a useful way to screen survivors who may be in need of a full neuropsychological assessment.

Neuropsychological functioning of children treated for acute lymphoblastic leukemia: impact of whole brain radiation therapy.

To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared. This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105. Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p < 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p < 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis. The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.

Assessment of Neuropsychological Late Effects in Survivors of Childhood Leukemia

The neurologic dysfunctions caused by treatment may affect health and quality of life in survivors of childhood leukemia. The objective of this study was to identify the neuropsychological late effects of leukemia treatment to provide an assessment about the degree and incidence of these late effects. Neurological and ophtalmological examination, cranial magnetic resonance imaging (MRI), auditory and neurocognitive tests, and questionnaires of quality of life were performed to 44 acute leukemia survivors at least 5 years after diagnosis. Median time since completion of chemotherapy was 7.5 years (2–18) and median age at the time of the study was 16.4 years (8–31). At least one or more late effects detected by physical examination (PE), neurological tests, or neurocognitive tests encountered in 80% of the patients, and 64% of the patients specified at least one complaint in the quality of life questionnaire. MRI revealed pathological findings in 18% and electroencephalogram (EEG) abnormalities were present in 9% of the patients. Evaluation of total intelligence scores revealed that 30% of patients’ IQ scores were <80 and 70% of the patients’ scores demonstrated neurocognitive dysfunctions. The patients >6 years at the time of diagnosis were found to have more psychological problems and higher rates of smoking and alcohol consumption. The most frequent complaint was headache and the most common problem in school was denoted as difficulty in concentration. Our study demonstrated that most of the survivors of childhood leukemia are at risk of developing neuropsycological late effects.

Neuropsychological late effects and rehabilitation following pediatric brain tumor

The modern era of research into the neurobehavioral late effects of pediatric brain tumor has been one of refinement in outcome measurement and advances in identification of risk factors for neurobehavioral impairment. There is no neuropsychological phenotype that encompasses all tumor types, treatments, and risk factors, though attention, working memory, processing speed, new learning, visuospatial and visuomotor functioning, executive functioning, and areas of academic achievement have been found to be at particular risk. Additional socioemotional and broader quality of life problems have been found in both survivors and their families. Past research has identified neuropsychological risk factors that include tumor location, radiation therapy and dose, certain chemotherapy agents, neurological complications, and demographic factors such as young age and female gender. Recent refinement in measurement of risk is improving our prediction of neurobehavioral outcomes. Neuropsychological and psychosocial interventions are now being developed, and the evidence base supporting these interventions is growing. Simultaneous advances in each of these areas will facilitate translation of research into risk-adapted rehabilitative care such that resources can be most effectively re-allocated and the best possible outcomes achieved.

Educational and vocational achievement among long‐term survivors of adolescent cancer in Germany

Adolescence involves graduating from school and preparing one's professional career. The accomplishment of these tasks may be hampered by the experience of cancer. This study investigates the educational and professional achievements of German long-term survivors of adolescent cancer. Adult survivors of cancer during adolescence (n = 820, age at onset between 15 and 18 years; M = 15.8, SD = 0.9 years; age at follow-up: M = 30.4, SD = 6.0 years) were recruited through the German Childhood Cancer Registry. They completed self-reports with standard items on their educational and vocational level and their current occupational situation. Outcomes were compared to an age-matched sample from the general population (German Socio-Economic Panel, n = 820, age: M = 30.4, SD = 6.7). Risk factors for educational and vocational underachievement were identified by subgroup analyses. Compared to peers from the general population, survivors of cancer during adolescence achieved higher educational and vocational levels. A higher proportion of survivors was employed; however, survivors were significantly older when starting their first occupation. Subgroup analyses revealed that neuropsychological late effects were associated with reduced rates of graduation from university and of employment among the survivors. No such effect of neuro-cognitive late effects occurred for high school graduation. Most German survivors of cancer during adolescence participate in school and vocational life without major difficulties. Problems particularly arise for survivors with neuropsychological sequelae. Further research should investigate whether these results can be attributed to the German support system for pediatric cancer patients or to sample effects.

Neuropsychological functioning of children treated with intensive chemotherapy followed by myeloablative consolidation chemotherapy and autologous hematopoietic cell rescue for newly diagnosed CNS tumors: An analysis of the Head Start II survivors

To evaluate the neuropsychological late effects amongst survivors treated on the Head Start II protocol between 1997 and 2003. Forty-nine patients (mean age 2.9 years) diagnosed with a malignant brain tumor underwent baseline neuropsychological assessment prior to autologous hematopoietic cell transplantation (AuHCT). Twenty-six survivors were retested after 3 years of follow-up as 20 patients did not survive. Patients were evaluated for intelligence, academic achievement, receptive language, visual-motor integration (VMI), learning/memory, social-emotional and behavioral functioning based upon age at testing. Overall intelligence and VMI at baseline were low average while verbal and non-verbal intelligence, academic achievement, and receptive vocabulary were in average range. Parents reported social-emotional and behavioral functioning within normal limits. Serial testing revealed Full Scale (FSIQ)/Mental Development Index (MDI), Verbal (VIQ), and Performance (PIQ) Intelligence to be generally stable over 3-year follow-up. Group-average analysis at follow-up demonstrated low average intelligence, academic achievement, receptive language, and VMI. Age at diagnosis was positively correlated with internalizing symptoms and visual immediate memory, while time since diagnosis was inversely correlated with FSIQ, VIQ, PIQ, reading and delayed verbal memory. Craniospinal irradiation (CSI) was avoided in two-thirds of patients. Induction, with or without intensification using intravenous methotrexate, followed by myeloablative consolidation chemotherapy with AuHCT, may avoid or delay CSI, with possible stabilization of neuropsychological functioning, including those younger at diagnosis. Continued follow-up is necessary to determine the preservation of neuropsychological, academic, social-emotional and behavioral functioning.

Neuropsychological Outcome in Chemotherapy-Only–Treated Children With Acute Lymphoblastic Leukemia

To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and systemic chemotherapy were included in a nationwide, prospective-longitudinal, sibling-controlled study. Patients and siblings completed three extensive neuropsychological assessments: at diagnosis, 3 to 6 months after completion of (2-year) treatment and 4.5 years after diagnosis. Assessments included measures of learning, memory, attention, speed, executive functioning, visual-constructive functioning, and fine-motor functioning. Multilevel analyses were applied to evaluate patients' performances over time and to compare patients to 29 siblings (median age of siblings at first assessment, 8.2 years; range, 4.5 to 12.6 years) and to normative data. No major differences were found in neuropsychological performance between patients and siblings, with both groups performing mainly in the normal range. The patient group as a whole, however, scored significantly lower than the siblings on complex fine-motor functioning at the last evaluation. Large practice effects were found for both patients and siblings in four of 11 tasks. Patients who uttered physical complaints (ie, pain and/or tiredness) at the first pretreatment assessment scored significantly lower than siblings on attention and speed at the last two evaluations. Despite intensive and potentially neurotoxic treatment, no evident negative, neuropsychological late effects were found 4.5 years after diagnosis, except for effects on complex fine-motor functioning. Both the large practice effects observed and the poorer performances on sustained attention for patients with physical complaints should be reckoned with in prospective, longitudinal neuropsychological research in children.

Social skills training interventions: A promising approach for children treated for brain tumors.

Pediatric brain tumors represent the second most frequently diagnosed malignancy of childhood (Strother et al., 2002). Children surviving brain tumors experience severe neurocognitive deficits as a result of medical late effects of the tumor and treatment (Butler & Mulhern, 2005; Ris & Noll, 1994). These children experience problems in psychosocial functioning as well, most notably, in the area of social competence. Despite the existence of research which suggests that social skills training interventions may improve social competence in other populations, the effectiveness of social skills training interventions for children surviving brain tumors remains understudied. This paper outlines the specific social deficits exhibited in children treated for brain tumors and their possible etiology, as well as existing social skills interventions and directions for future research. Poor Social Competence is an Outcome in Children Treated for Brain Tumors As life expectancy and survival rates for children with brain tumors have improved over the past two decades, increasing focus has been placed on long-term outcomes and adaptation in this population (Peterson & Drotar, 2006). Although the psychosocial outcomes for these patients are beginning to receive more attention, they remain comparatively less explored than the neuropsychological sequelae and late effects of treatment (Fuemmeler, Elkin, & Mullins, 2002; Peterson & Drotar, 2006). One psychosocial outcome consistently reported among children surviving brain tumors is poor social competence (Barakat et al., 2003; Fuemmeler, Elkin, & Mullins, 2002; Mulhern, Carpentieri, Shema, Stone, & Fairclough, 1993; Mulhern, Hancock, Fairclough, & Kun 1992; Radcliffe, Bennett, Kazak, Foley, & Phillips 1996; Ris & Noll, 1994; Vannatta, Gartstein, Short, & Noll., 1998). In fact, although a recent review by Fuemmeler and colleagues (2002) of 31 studies focused on different areas of psychosocial adjustment of survivors of childhood brain tumors yielded mixed findings regarding the adjustment of these children, the authors did conclude that children treated for brain tumors are indeed at risk for significant deficits in social competence. Definition of Social Competence Multidimensional in nature, the term social competence was conceptualized by Gresham (1986) as incorporating domains such as social skills, adaptive behavior, and peer acceptance (Elliott & Busse, 1991; Fuemmeler et al., 2002). In their review of the literature regarding social competence in children with central nervous system (CNS) related conditions, Nassau and Drotar (1997) highlighted Cavell's (1990) model of children's social competence as a useful framework for describing specific facets of social competence relevant to children with these conditions. As described by Nassau and Drotar (1997), the domains of social competence included in the model are: social adjustment, social performance, and social skills (Cavell, 1990). Specific Deficits of Social Competence in Children with Brain Tumors Studies assessing social competence in children with brain tumors suggest deficits in all of these areas, although oftentimes unclearly delineated (Fuemmeler et al., 2002). For example, children treated for brain tumors have been reported to have higher rates of behavior problems and less social competence on the Child Behavior Checklist (CBCL; Achenbach & Edelbrock, 1983) than children with other cancers (Carpentieri et al., 1993; Fossen, Abrahamson, & Storm-Mathisen, 1988). In addition, in a study of 29 children post-treatment for hypothalamic/chiasmatic tumors, survivors displayed increased behavior problems and decreased social and academic competence as compared to a normative sample (Foley, Barakat, herman-Liu, Radcliffe, & Molloy, 2000). Moreover, during the development of the Miami Pediatric Quality of Life Questionnaire (MPQOLQ) Armstrong and colleagues (1999) found that children with brain tumors had significantly lower scores in the domain of social competence, which included engagement in and enjoyment of activities, as well as involvement with a peer group. …

Neurocognitive Interventions for Children and Adolescents Surviving Cancer

It is well recognized that many cures for childhood leukemia and brain tumors entail some relatively permanent neurocognitive and psychological costs to the patient and family. As cure rates have improved over the past three decades, increasing efforts have been directed toward reducing treatment-related late effects. The particular focus of this review will be on interventions for the neuropsychological late effects associated with the treatment of acute lymphoblastic leukemia (ALL) and malignant brain tumors. We will first briefly review current approaches to the medical treatment of ALL and brain tumors to provide an appreciation of potential sources of brain injury. We will then summarize the existing literature on types of neuropsychological deficits found among survivors, with special attention to variables that place some children at greater risk. Then, there will be a discussion of approaches to intervention for these deficits-specifically, cognitive remediation, pharmacology, and ecological alterations in the classroom. Finally, we will present directions for future research in the field.