Dataset Information

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction.

ABSTRACT:

Background

Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20-25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups' current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.

Methods

Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT?+?CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the ?, ?, ?1, ?2, ? and ? frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.

Results

In the CT?+?CRT group, relative ? power was slightly increased (p?=?0.069) and ?2 power was significantly decreased (p?=?0.006). The CT?+?CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional ? and ?2 powers (0.471?ConclusionsThe tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early-onset dementia. The CT group showed no signs of early aging.

SUBMITTER: Daams M

PROVIDER: S-EPMC3517522 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction.

Daams Marita M Schuitema Ilse I van Dijk Bob W BW van Dulmen-den Broeder Eline E Veerman Anjo Jp AJ van den Bos Cor C de Sonneville Leo Mj LM

BMC neurology 20120828

<h4>Background</h4>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20-25 years later, giving a much ...[more]

PMID: 22928913

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Project description:BackgroundProphylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse.MethodsWe conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted from treatment in all children with newly diagnosed ALL. A total of 498 patients who could be evaluated were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission-induction treatment. The duration of continuous complete remission in the 71 patients who previously would have received prophylactic cranial irradiation was compared with that of 56 historical controls who received it.ResultsThe 5-year event-free and overall survival probabilities for all 498 patients were 85.6% (95% confidence interval [CI], 79.9 to 91.3) and 93.5% (95% CI, 89.8 to 97.2), respectively. The 5-year cumulative risk of isolated CNS relapse was 2.7% (95% CI, 1.1 to 4.3), and that of any CNS relapse (including isolated relapse and combined relapse) was 3.9% (95% CI, 1.9 to 5.9). The 71 patients had significantly longer continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remained in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blast cells at diagnosis and a high level of minimal residual disease (> or = 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection.ConclusionsWith effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted from the treatment of childhood ALL. (ClinicalTrials.gov number, NCT00137111.)

Project description:Statistical power is key for robust, replicable science. Here, we systematically explored how numbers of trials and subjects affect statistical power in MEG sensor-level data. More specifically, we simulated "experiments" using the MEG resting-state dataset of the Human Connectome Project (HCP). We divided the data in two conditions, injected a dipolar source at a known anatomical location in the "signal condition", but not in the "noise condition", and detected significant differences at sensor level with classical paired t-tests across subjects, using amplitude, squared amplitude, and global field power (GFP) measures. Group-level detectability of these simulated effects varied drastically with anatomical origin. We thus examined in detail which spatial properties of the sources affected detectability, looking specifically at the distance from closest sensor and orientation of the source, and at the variability of these parameters across subjects. In line with previous single-subject studies, we found that the most detectable effects originate from source locations that are closest to the sensors and oriented tangentially with respect to the head surface. In addition, cross-subject variability in orientation also affected group-level detectability, boosting detection in regions where this variability was small and hindering detection in regions where it was large. Incidentally, we observed a considerable covariation of source position, orientation, and their cross-subject variability in individual brain anatomical space, making it difficult to assess the impact of each of these variables independently of one another. We thus also performed simulations where we controlled spatial properties independently of individual anatomy. These additional simulations confirmed the strong impact of distance and orientation and further showed that orientation variability across subjects affects detectability, whereas position variability does not. Importantly, our study indicates that strict unequivocal recommendations as to the ideal number of trials and subjects for any experiment cannot be realistically provided for neurophysiological studies and should be adapted according to the brain regions under study.

Dataset Information

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction.

Background

Methods

Results

Publications

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction.

Similar Datasets

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