Donna R. Copeland

Attentional processes and their remediation in children treated for cancer: A literature review and the development of a therapeutic approach

It is now generally accepted that central nervous system treatments for childhood cancer can result in significant cognitive impairment, most commonly in the areas of attention/concentration. We review the literature on attentional and neurocognitive deficits in this population, and also efforts to remediate attentional deficits in other brain injured populations. It was our goal to develop an innovative, psychologically based outpatient rehabilitation program that would improve dysfunctional attentional processes and associated neuropsychological deficits. The characteristics of this program and a pilot study of its effectiveness are described. Participants were 31 off-therapy cancer survivors with documented attention deficits. Twenty-one completed the cognitive remediation program (CRP) and 10 served as comparisons. All participants completed a test of vigilance attention, 2 tests with an attentional component, and an arithmetic academic achievement measure. When the scores of the 2 groups were compared, the CRP group exhibited statistically significant improvement on all attentional measures. In contrast, the comparison group did not manifest any significant changes. Neither group demonstrated statistically significant changes on the arithmetic achievement test. We believe that the CRP has potential for improving attention/concentration, but generalization to academic achievement remains unproven. Phase 3 clinical trials and the documentation of long-term treatment gains are needed. Furthermore, it will be necessary to demonstrate the ecological validity of the CRP. With these caveats, this therapeutic approach may be helpful in other populations of cognitively impaired children and young adults, such as patients who have suffered traumatic brain injury.

A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy.

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35% female, 18% Hispanic, 10% African American, 64% Caucasian, 8% other) who were at least 1 year off treatment and who manifested an attentional deficit. They were enrolled at 7 sites nationwide. Two thirds of the participants were randomly assigned to cognitive remediation. All participants were assessed using a battery of academic achievement/neurocognitive tests and parent/teacher measures of attention. The CRP resulted in parent report of improved attention and statistically significant increases in academic achievement. Effect sizes were modest but were comparable with those for other clinical trials of brain injury rehabilitation and for psychological interventions in general. The CRP is presented as a potentially beneficial treatment for many survivors of pediatric cancer. Long-term clinical significance remains unproven. Further work is needed to improve effect sizes and treatment compliance and to address the needs of other populations with pediatric brain injury.

Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children

This article reviews 41 studies of the effects of prophylactic CNS treatment on the neurobehavioral development of children with cancer. This research is classified according to studies of (a) children in treatment; (b) long-term survivors; and (c) longitudinal follow-ups of children from the time of diagnosis. Studies vary considerably in design, sample, and outcome variables, so firm conclusions regarding the morbidity of CNS prophylaxis are not currently possible. However, the studies do suggest that CNS prophylaxis does impair cognitive development, particularly when cranial radiation therapy is part of the treatment. There is also evidence of greater impairment in younger children and some suggestion of more frequent impairment of non-language skills relative to language skills. The possible relationships among age, radiation, and non-language cognitive skills may be linked to disruption of white matter CNS structures apparent on autopsy and cerebral tomography following treatment.

Using Problem-Solving Skills Training to Reduce Negative Affectivity in Mothers of Children With Newly Diagnosed Cancer: Report of a Multisite Randomized Trial.

Mothers of children with cancer experience significant distress associated with their childrens diagnosis and treatment. The efficacy of problem-solving skills training (PSST), a cognitive-behavioral intervention based on problem-solving therapy, was assessed among 430 English- and Spanish-speaking mothers of recently diagnosed patients. Participants were randomized to usual psychosocial care (UPC; n=213) or UPC plus 8 sessions of PSST (PSST; n=217). Compared with UPC mothers, PSST mothers reported significantly enhanced problem-solving skills and significantly decreased negative affectivity. Although effects were largest immediately after PSST, several differences in problem-solving skills and distress levels persisted to the 3-month follow-up. In general, efficacy for Spanish-speaking mothers exceeded that for English-speaking mothers. Findings also suggest young, single mothers profit most from PSST.

Neurocognitive Development of Children After a Cerebellar Tumor in Infancy: A Longitudinal Study

PURPOSE To assess the long-term neuropsychologic effects experienced by children who have tumors in the cerebellum that are diagnosed and treated during infancy. PATIENTS AND METHODS Twenty-seven children with posterior fossa tumors diagnosed at less than 36 months of age were assessed prospectively with a comprehensive set of age-appropriate tests. Group means and SDs are reported for assessments conducted at diagnosis (analysis 1) and at the most recent follow-up appointment (analysis 2). Cognitive developmental growth curves were derived from the prospective data (analysis 3) using mixed model regression analyses and controlling for age at diagnosis and socioeconomic status. RESULTS In the first analysis, eight of 11 infants at diagnosis scored within normal limits on all neuropsychologic domains, except for motor skills, which were impaired. In the second analysis, mean scores at the most recent follow-up of 21 of 27 patients were mostly in the normal range; however, group comparisons between those who had (n = 7) and had not (n = 14) been treated with cranial radiation therapy (CRT) showed that patients in the irradiated (CRT) group scored significantly lower than those in the nonirradiated (No-CRT) group on verbal intelligence quotient (IQ) and in the motor domain. In the third analysis (growth curves of CRT and No-CRT groups), statistically significant differences in slope were found on verbal IQ, performance IQ, perceptual-motor skills, language, and attention/executive skills. Slopes on the fine-motor domain were similar; both groups declined at approximately the same rate. CONCLUSION Neurocognitive development and outcome of children with cerebellar tumors diagnosed in infancy is very positive among those who were treated with surgery and chemotherapy. Declines in performance across time were minimal, and scores tended to remain within normal limits. By itself, a cerebellar tumor in infancy does not seem to have a significant impact on children. However, those who received CRT as part of their treatment are likely to have neurocognitive and psychosocial deficits that require remediational interventions.

Neuropsychologic effects of chemotherapy on children with cancer: a longitudinal study.

PURPOSE A prospective study was conducted to assess the effects of chemotherapy for cancer on childrens long-term neuropsychologic status. PATIENTS AND METHODS Ninety-nine children who received no cranial radiation therapy (CRT) completed four annual neuropsychologic assessments. Fifty-one patients received intrathecal (IT) chemotherapy (ITC); 48 received no CNS treatment. These two groups were compared using repeated-measures analysis of variance on IQ, memory, language, freedom from distractibility, academic achievement, executive functions, and fine-motor, perceptual-motor, and tactile-spatial skills. In addition, 51 of the sample of 99 patients had been examined 5 to 11 years after diagnosis. Their data were analyzed to evaluate the longer-term effects of chemotherapy. The predictability of demographic and medical variables on neuropsychologic outcome at 3-year and long-term follow-up study were assessed using multiple regression techniques. RESULTS Overall, the effects of chemotherapy in the absence of CRT appear to be slight. Patients who received ITC and intravenous (IV) methotrexate declined slightly on perceptual-motor skills, but were still well within the normal range. Both groups, regardless of treatment, declined on academic achievement tests, although not to a statistically significant degree. Age effects were found on performance IQ (PIQ) and perceptual-motor skills. Socioeconomic status (SES) correlated with a large number of variables. Sex effects were not significant. CONCLUSION The present results are largely consistent with previous findings for nonirradiated groups. Treatment effects from ITC are slightly more apparent 5 to 11 years after diagnosis than at 3-year follow-up evaluation but this does not constitute a clinically meaningful difference. More noticeable are academic declines among all groups, regardless of treatment.

Problem-solving skills training for mothers of children with newly diagnosed cancer: a randomized trial.

ABSTRACT. Mothers of children with serious illnesses have lower levels of well-being than mothers in the general population. Problem-solving therapy (PST), a cognitive-behavioral intervention, has been shown to be effective in treating negative affectivity (depression, anxiety) and other manifestations of reduced well-being. This report describes a problem-solving skills training (PSST) intervention, based on problem-solving therapy, for mothers of newly diagnosed pediatric cancer patients. Ninety-two mothers were randomly assigned to receive PSST or to receive standard psychosocial care (Control Group). After the 8-week intervention, mothers in the PSST Group had significantly enhanced problem-solving skills and significantly decreased negative affectivity compared with controls. Analysis revealed that changes in self-reports of problem-solving behaviors accounted for 40% of the difference in mood scores between the two groups. Interestingly, PSST had the greatest impact on improving constructive problem solving, whereas improvement in mood was most influenced by decreases in dysfunctional problem solving. The implications of these findings for refinement of the PSST intervention and for extension to other groups of children with serious illnesses are discussed.

Sibling adaptation to childhood cancer collaborative study: prevalence of sibling distress and definition of adaptation levels

A multisite collaborative study assessed the frequency and intensity of emotional/behavioral distress in siblings of children with cancer. A sample of 254 siblings, aged 4 to 18 years, and their parents completed interviews and self-report measures 6 to 42 (average 22.5) months after diagnosis of cancer in a brother or sister. Matched controls were obtained from respondents to the Child Health Supplement of the National Health Interview Survey administered in 1988 (CHS88). Before diagnosis, the prevalence of parent-reported emotional/behavioral problems among siblings was similar to that in the general population (7.7% vs 6.3%; p = not significant). After diagnosis, prevalence rose to 18% among siblings. When siblings were grouped according to the presence or absence of problems exacerbated by and/or arising after diagnosis, four levels of adaptation, consistent with scores on the Behavior Problem Scales from the CHS88, emerged. This differentiation may help explain inconsistencies in sibling response reported previously and provides a framework for investigating factors that enhance adaptation. J Dev Behav Pediatr 15:353–366, 1994. Index terms: chronic illness, childhood cancer, siblings, adaptation, coping, psychosocial stress.

MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children

Infants and young children who have brain tumors have a poor rateof survival and high treatment associated morbidity. A trial of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone(MOPP) was performed to test the hypothesis that replacingradiotherapy with chemotherapy would improve survival and decreaselong term morbidity of infants who have brain tumors. Between 1976 and1988, 17 consecutive children less than 36 months old when diagnosed with medulloblastoma or ependymoma were treatedwith MOPP chemotherapy as primary therapy following surgical excision or biopsy of the tumor. Radiotherapy was reserved for recurrent disease. Ten of 17 children have survived without evidence of disease: medulloblastoma, eight of 12 with median survivaltime of 10.6 years (range, 6.2 to 15.2 yrs); and ependymoma, 2of 5 (at 13.0 and 16.0 yrs). Four of the 10 children with medulloblastomaand ependymoma who relapsed are now disease free at 7.5, 11.7, 12.2 and 13.5 yrs post relapse after receiving salvagetherapy with cisplatin (n = 1) or irradiation (n = 3). All relapsesoccurred within 26 months of diagnosis. Data on growth demonstrated heightless than the 5th percentile in all children who received cranial irradiation compared to 25 to 95th percentile for nonirradiated children. Intellectual ability for the groupwho did not require radiation was within normal range (mean IQ 100.1) and stable across annual assessments. Those who required radiation hadlower IQs which continued to decline over time (mean IQ 85 at mean age of 5.8 years, declining to 63 at 10 years).In young children with brain tumors, primary chemotherapy with MOPP, omitting radiotherapy, provides improved neurodevelopmental outcome and survival.

Neuropsychological Profile of Children With Neurofibromatosis, Brain Tamor, or Both

Neurofibromatosis type 1, a common autosomal dominant genetic disorder, is associated with numerous physical and medical anomalies as well as an increased incidence of learning disability. Tumors of the central nervous system have been estimated to occur in 15%, but their contribution to neuropsychological status is unknown. This study examines the relative contribution of neurofibromatosis and brain tumor to the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological and behavioral tests was administered to a group of 65 children with neurofibromatosis type 1. Fourteen were then matched on demographic variables with two other groups of children who had either a brain tumor in addition to neurofibromatosis or a brain tumor alone. The two brain tumor groups were also matched on tumor type, location, and therapy. Mean scores of the neurofibromatosis-brain tumor group were generally the lowest of the three groups; those of the brain tumor group were highest, and performance of the neurofibromatosis group was generally between the other two groups. These results suggest that neurofibromatosis is, by itself, associated with significant cognitive morbidity, but that the severity of the problems is increased somewhat if a brain tumor is also present. (J Child Neurol 1994;9:368-377).