Raymond K. Mulhern

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Psychological functioning of adolescent and young adult survivors of pediatric malignancy

OBJECTIVEnTo assess the psychological functioning of adolescent and young adult survivors of pediatric malignancy, and identify risk factors for maladjustment.nnnDESIGNnPatients age > or = 14.5 years (N = 161) receiving surveillance follow-up at a major pediatric cancer center completed the SCL-90-R, a self-report measure of psychological symptomatology. Comparisons were made with the normative standardization sample, and the relationship of selected demographic and medical variables with psychological distress was explored using logistic regression analyses.nnnRESULTSnSurvivors mean scores on all SCL-90-R subscales were lower than those of the standardization sample, and the distribution of scores on the Anxiety, Psychoticism, Global severity Index, and Positive Symptom Total scales were significantly below normative values. No SCL-90-R subscale displayed an excessive frequency of clinically elevated scores. For patients who displayed clinical elevations on the SCL-90-R, three factors were identified which were associated with increased risk of maladjustment; older patient age at follow-up, more frequent disease relapse, and more severe functional impairment.nnnCONCLUSIONSnThis cohort of childhood cancer survivors is characterized by very low levels of psychological distress and significantly better psychological health than would be expected according to normative data. These findings contrast with those of another study from the same institution in which a fourfold increase in social and behavioral problems was found amongst younger survivors, in the age range 7-15. The use of self-report vs. parent-report, and the potential influence of repressive adaptation on the self-reports of pediatric cancer survivors, are raised as possible explanations for these findings.

Neurocognitive late effects in pediatric cancer.

As survival rates for the most prevalent types of childhood cancer have dramatically improved over the past three decades, the concept of “cure” has evolved to include optimizing the quality of life among survivors. Although significant progress has been made in addressing some adverse late effects of treatment that limit quality of life, such as endocrinopathies, other late effects remain problematic. This paper will review neurocognitive late effects as defined by problems with thinking, learning, and remembering among survivors of childhood cancer. After defining the neurocognitive phenotype that characterizes many such children, we will review the etiology and risk factors for damage to the central nervous system associated with childhood cancer and its treatment. We will then discuss methods of pharmacological, behavioral, and ecological intervention that may be helpful in reducing learning problems among surviving children. Finally, we will identify areas of future research that will be critical to the elimination of neurocognitive late effects in childhood cancer survivors and the resources needed to implement such research.

Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood.

Children surviving treatment for malignant brain tumors commonly have problems maintaining their premorbid levels of intellectual development and academic achievement. Our group has been especially interested in the effects of treatment on normal appearing white matter (NAWM) on MRI and the influence of NAWM volumes on neurocognitive functioning. The present study assessed NAWM and attentional abilities among 37 long-term survivors of malignant brain tumors, ranging in age from 1.7 to 14.8 (Mdn = 6.5) years at diagnosis, who had been treated with cranial radiation therapy with or without chemotherapy 2.6 to 15.3 (Mdn = 5.7) years earlier. On the Conners Continuous Performance Test, the Overall Index and 7 of the other 10 indices were significantly deficient compared to age- and gender-corrected normative values. After statistically controlling for the effects of age at diagnosis and time elapsed from treatment, 5 of the 8 indices were significantly associated with cerebral white matter volumes and/or specific regional white matter volumes of the prefrontal/frontal lobe and cingulate gyrus. No gender effects were observed. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood.

Effectiveness of psychological intervention for children and adolescents with chronic medical illness: a meta-analysis.

Outcomes from 42 studies of psychological interventions for children and adolescents with chronic medical conditions were analyzed using meta-analysis. Studies were divided into the four intervention categories suggested by LaGreca and Varni (1993), Disease Management, Emotional/Behavioral Problems, Health Promotion, and Prevention. Results supported overall effectiveness of psychological interventions, with an effect size (ES) of 1.12, as well as maintenance of treatment gains for at least 12 months posttreatment. Psychological interventions directed at disease-related or emotional/behavioral problems were both found to be effective, although too few studies of health promotion or disease prevention interventions were identified to be included in the analysis. Effectiveness of behavioral interventions, which were most heavily represented in the sample, demonstrated similar effects for disease management (ES = 1.20) and emotional/behavioral (ES = 1.03) problems. Although disease type, severity, and duration did not affect intervention effectiveness, some influences of patient age and gender were noted across studies. Recommendations for further intervention studies and improvements in study design are discussed.

Chemotherapy-induced nausea and emesis in pediatric cancer patients: An analysis of coping strategies

We investigated the preference and perceived efficacy of coping strategies used to manage chemotherapy-induced nausea and emesis in 57 pediatric oncology patients. Over 85% of children preferred Wishful Thinking, Emotional Regulation, and Distraction to cope with nausea, and Emotional Regulation to manage emesis. Stepwise logistic regression analyses revealed that the coping strategy used and its perceived efficacy depended upon patient age and gender, severity of symptom distress, time elapsed from last chemotherapy, experience, and whether nausea or emesis was the identified problem. Successful copers, defined as those reporting high coping efficacy and minimal distress, composed only 25% of the sample. These children most often used Problem Solving combined with Social Support for symptom management. Successful coping was also associated with lower emetogenic potential of chemotherapy. The significance of these results is discussed for identifying high-risk children who may benefit from coping interventions.

Feasibility and Efficacy of Preirradiation Chemotherapy for Pediatric Brain Tumors

Preirradiation chemotherapy is a potentially important component of combined treatment for brain tumors; however, concerns over its side effects and antitumor activity have impeded its evaluation in clinical trials. To determine the feasibility of administering such therapy to children, we assessed the responses of 38 brain tumor patients (median age, 2 years) to 12 weeks of combination chemotherapy given after surgical resection but before irradiation. Transient myelosuppression was noted in all patients, but was not associated with infections or complications of surgical wounds. The ability of the patients to perform activities of daily life, as rated with the Karnofsky performance scale, was either improved (n = 14) or unchanged (n = 18) at the end of the evaluation period. In the remainder of the group, functional deterioration was clearly related to causes other than drug treatment. Prior chemotherapy did not compromise the delivery of radiation except for a brief interruption of spinal irradiation in 3 patients. Objective responses to chemotherapy, defined as a greater than 50% decrease in tumor masses, occurred in 16 of the 31 patients who had subtotal resections; only 6 patients in the entire group showed disease progression during the 12 weeks of drug administration. We conclude that chemotherapy of the type used in this study is well tolerated and produces beneficial effects in children with brain tumors.