Analysis of surgical and MRI factors associated with cerebellar mutism.

The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A total of 22 patients (11 with and 11 without CM) were included. Medulloblastoma was the most common pathology among CM patients (91%); the remaining 9% were diagnosed with a pilocytic astrocytoma. Tumor attachment to the floor of the fourth ventricle (OR 6; 95% CI 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR 5; 95% CI 0.5-236.5) were found to have the highest measures of association with CM. Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia have a relatively higher prevalence in patients with CM. Collectively, our work calls for a larger multi-institutional cohort study of CM patients to encourage further investigation of the determinants and management of CM in order to potentially minimize its development and predict onset.

Long-Term Social Outcomes of Hyperfractionated Radiation on Childhood ALL Survivors.

BACKGROUND/OBJECTIVES: Childhood cranial radiation has irreversible neurocognitive effects. Hyperfractionated radiation therapy (HFX) for acute lymphoblastic leukemia (ALL) was randomized against conventionally fractionated radiation therapy (CFX) in the DFCI 87-01/91-01 trials attempting to minimize these effects. When neurocognitive testing 8-year posttreatment demonstrated no difference, this strategy was abandoned. The objective of this study was to evaluate late social outcomes among patients who received HFX compared to CFX as part of the DFCI 87-01/91-01 trials. METHODS: This retrospective chart review examined all patients treated according to the DFCI 87-01/91-01 trials at the McMaster Children's Hospital in Hamilton, Canada. Patients <18 years at diagnosis and who have attended follow-up clinic since January 1, 2000 were included in this study. Social outcomes and IQ test results were examined for trends. Demographics and outcomes were presented with descriptive statistics. RESULTS: We identified 57 DFCI 87-01/91-01 trial participants: 14 received HFX, 29 received CFX, and 14 received no radiation. There were no demographic differences between the groups. HFX survivors were more likely to be living independently (64% vs. 28%, P = 0.02) and engaged in long-term relationships (57% vs. 25%, P = 0.04) than CFX. Nonsignificant trends suggested that HFX survivors may be more financially independent, employed full-time, had fewer educational difficulties in school, and higher scores on neuropsychological testing. Data trends, although not significant, persisted in logistic regression analysis when accounting for age. CONCLUSION: Long-term social outcomes were better among ALL survivors who received HFX than CFX. A wider study involving all patients enrolled on DFCI 87-01/91-01 protocols should be conducted to reconsider radiation protocols for ALL.

Neuropsychological late effects of treatment for acute leukemia in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) have an elevated risk of developing acute leukemia, but little is known about treatment-related neuropsychological morbidity because they are systematically excluded from research in this area. The current study investigated neuropsychological outcomes in children with DS treated for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) compared to children with DS with no history of cancer. PROCEDURE: Participants were 4 to 17 years of age at testing and were administered measures of intelligence, academic achievement, language, visual-motor and fine-motor skills, and adaptive function. Patients had been off treatment for at least 2 years. RESULTS: The AML group (N = 12) had significantly lower verbal intelligence and receptive vocabulary compared to controls (N = 21). By contrast, the ALL group (N = 14) performed significantly worse than controls on measures of verbal intelligence, spelling, receptive and expressive vocabulary, visual-motor skills, and adaptive function. CONCLUSIONS: Patients with DS treated for AML may have specific post-treatment morbidity in verbal function, whereas those treated for ALL have broader morbidity affecting multiple neuropsychological domains and overall adaptive function. We hypothesize that the broader impairment profile of ALL survivors may be related to a combination of the longer duration of central nervous system-directed treatment for ALL compared to AML and the concomitant limited access to intervention opportunities during active treatment.

Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute All Consortium Protocol 00-01.

BACKGROUND: Dexamethasone is more efficacious than prednisone in the treatment of acute lymphoblastic leukemia (ALL), but has also been associated with greater toxicity. We compared neuropsychological outcomes for patients treated on DFCI ALL Consortium Protocol 00-01, which included a randomized comparison of the two steroid preparations during post-induction therapy in children and adolescents with ALL. PROCEDURE: Between 2000 and 2005, 408 children with standard-risk or high-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 00-01 were randomly assigned to prednisone or dexamethasone administered as 5-day pulses every 3 weeks for 2 years, beginning at week 7 of treatment. Blinded neuropsychological testing was completed for 170 randomized patients (prednisone, N = 76; dexamethasone, N = 94), all of whom were in continuous complete remission after completion of therapy. RESULTS: Outcomes were comparable for most variables, although patients on the dexamethasone arm performed more poorly on a measure of fluid reasoning (P = 0.02). They also tended to be more likely to be enrolled in special education (dexamethasone, 33% vs. prednisone, 20%, P = 0.09). CONCLUSIONS: Dexamethasone has well documented benefit in treatment of ALL. Although formal testing provided little indication of increased risk for neurotoxicity relative to prednisone, the somewhat greater utilization of special education services by patients treated with dexamethasone merits further investigation.

Neuropsychological outcomes of standard risk and high risk patients treated for acute lymphoblastic leukemia on Dana-Farber ALL consortium protocol 95-01 at 5 years post-diagnosis.

BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana-Farber Cancer Institute (DFCI) Consortium ALL Protocol 95-01. We also evaluated their performance relative to normative expectations. PROCEDURE: Between 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95-01, 298 of whom were eligible for neuropsychological follow-up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post-diagnosis for 211 patients (70.8%; ages 6-25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission. RESULTS: Test scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range. CONCLUSIONS: HR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects.

Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01.

PURPOSE: We evaluated late neuropsychological toxicity in children treated for standard-risk acute lymphoblastic leukemia (ALL) who were randomly assigned to receive either cranial radiation therapy (CRT) with double intrathecal (IT) chemotherapy or intensive triple IT chemotherapy (no CRT) as CNS-directed therapy. PATIENTS AND METHODS: Between 1996 and 2000, 164 children with standard-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 were randomly assigned to receive either 18 Gy CRT delivered in twice daily fractions (0.9 [DOSAGE ERROR CORRECTED] Gy) with double IT therapy (methotrexate and cytarabine) or intensive triple IT drug (methotrexate, cytarabine and hydrocortisone) without CRT. Neuropsychological testing was completed at a median 6 years postdiagnosis for 79 children (CRT, n = 39; triple IT, n = 40), all of whom were in continuous complete remission. RESULTS: Cognitive function for both groups was solidly in the average range, with no consistent group differences in basic cognitive skills. Children treated on the CRT plus double IT arm did, however, exhibit less fluent output and were less effective at modulating their behavior by parent report. CONCLUSION: This randomized trial revealed only subtle differences 6 years after diagnosis between children who received CNS therapy as CRT plus double IT drug or as intensive triple IT drug. In most situations where comparable therapeutic efficacy can be achieved without CRT, it is preferable to do so. Where therapeutically necessary, however, CRT at lower doses may not add risk for significant neurotoxicity.

The development of an off-therapy needs questionnaire and protocol for survivors of childhood cancer.

The purpose of this project was to obtain input from the families of survivors of childhood cancer regarding their needs surrounding the "coming off treatment" (COT) period. A questionnaire was developed to record their needs, their wishes, and their satisfaction surrounding this period of time. Closer examination of the time surrounding COT was undertaken in an attempt to enhance this area of service for patients and families in our clinic setting. Establishing a structured protocol is likely to alleviate some of the anxiety that surrounds this time for families and help us to provide better continuity of care. After identifying a cohort of patients and families, the reason for the survey was explained and they were asked to complete the questionnaire before they left the clinic setting. At the completion of the study, 82% of the cohort had been approached, and 100% of this group had completed the survey (n = 41). Less than 50% of participants felt they had had a formal "coming off treatment" review but, of that same group, 89% were satisfied with the process. Participants identified areas of importance and health care professionals who they would like involved in the COT process. After reviewing the responses to the questionnaires, the decision was made to proceed in preparing a COT protocol.