Changes in Cerebral Cortex of Children Treated for Medulloblastoma

Liu, Arthur K.; Marcus, Karen J.; Fischl, Bruce; Grant, P. Ellen; Poussaint, Tina Young; Rivkin, Michael J.; Davis, Peter E.; Tarbell, Nancy J.; Yock, Torunn I.

doi:10.1016/j.ijrobp.2007.01.034

Cited by 34 publications

(27 citation statements)

References 48 publications

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“…Moreover, it seems likely that the changes in cortical thickness and WM volume are related (48), but which is the most important in manifesting late effects still needs to be determined. In addition, we noted that the changes in average cortical thickness that we observed after CRT were opposite to those reported previously (49), indicating need for further verification.…”

Section: Discussioncontrasting

confidence: 99%

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

Nieman

Guzman

Gazdzinski

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussioncontrasting

confidence: 99%

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

Nieman

Guzman

Gazdzinski

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…However, the MMSE has low sensitivity to detect cognitive dysfunction in brain tumor patients [21]. For instance, MMSE does not assess domains often disrupted by treatment effects such as psychomotor speed and executive functions, and the rate of IQ decline is well known to be associated with several risk factors, including a particularly young age at the time of treatment [22].…”

Section: Discussionmentioning

confidence: 99%

Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience

et al. 2011

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In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

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“…Thus we conclude that chemoradiation may disrupt or delay the normal process of cortical thinning and potentially impair optimal cognitive development. It is of interest that a previous, cross-sectional study that compared cortical thickness of MB patients to healthy controls showed decreased cortical thickness in MB patients [2]. To reconcile these observations, we postulate that the use of absolute cortical thickness as done in the cross-sectional study, without a temporal reference lacks definitive value.…”

Section: Discussionmentioning

confidence: 96%

“…Dosimetric-epidemiological analysis from the childhood cancer survivorship study reveals radiation to the temporal lobe to be particularly associated with neuropsychological late effects in a dose-dependent manner, and in complementary domains not limited to memory impairment, such as social functioning, emotional well-being and task efficiency [1]. While thinner temporal lobe gray matter in MB patients has been identified in a previous, cross-sectional study comparing absolute differences from healthy controls, rates of longitudinal cortical thickness change over time are more robustly correlated with neurocognitive development and have not been studied in patients receiving chemoradiation [2, 3]. Following initial cortical growth during infancy through early childhood, cortical thinning during late childhood through adolescence is a normal developmental process associated with synaptic pruning, the consolidation of neuronal synapses that is essential for learning, and for which the effects of chemoradiation are unknown yet may be amenable to medical interventions with agents already in clinical trials [3].…”

Section: Introductionmentioning

confidence: 99%

Chemoradiation impairs normal developmental cortical thinning in medulloblastoma

Kundu

Durkee

et al. 2017

J Neurooncol

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Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA −0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.

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Changes in Cerebral Cortex of Children Treated for Medulloblastoma

Cited by 34 publications

References 48 publications

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience

Chemoradiation impairs normal developmental cortical thinning in medulloblastoma

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