Quality of Life in Children with Primitive Neuroectodermal Tumors (Medulloblastoma) of the Posterior Fossa

Packer, Roger J.; Sposto, Richard; Atkins, Thomas; Sutton, Leslie N.; Bruce, Derek A.; Siegel, Kathy R.; Rorke, Lucy B.; Littman, Philip; Schut, Luis

doi:10.1159/000120325

Cited by 94 publications

(47 citation statements)

References 11 publications

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“…This finding confirms that clinical neurologic sta tus, especially sensory and motor function, should be con sidered in the interpretation of IQ scores as an index of treatment toxicity. We as well as other investigators have noted the limitations that chronic neurological deficits place on intellectual development as measured by tradi tional IQ tests [11,13]. Indirect effects of sensory and motor deficits on the child's ability to acquire informa tion at an age-appropriate rate may result in lowered IQ over time in the absence of primary cognitive impair ment.…”

Section: Discussionmentioning

confidence: 77%

Quality of Survival among Children Treated for Brain Stem Glioma

et al. 1994

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In order to describe the status of long-term survivors of brain stem glioma, neuropsychological and behavioral measures were obtained a median of 2.5 (range 1.5-5.6) years after diagnosis from 16 survivors of 51 consecutively diagnosed children with brain stem glioma between 1983 and 1991. Among 11 children with dorsally exophytic tumors, 7 were treated with surgery alone (SRG) and 4 received conventionally fractionated local cranial radiation therapy (CFRT; 54-56 Gy) to the brain stem following surgery, 3 of these because of recurrent disease. Five others with diffusely infiltrative brain stem tumors received hyperfractionated radiation therapy (HFRT; 70.2 Gy) to the brain stem; 4 following biopsy or limited resection and 1 without prior surgery. IQs of children in the CFRT (mean 89, SD 24.4) and HFRT (mean 85, SD 12.7) groups were not significantly different. Children in the SRG group had significantly higher IQs (mean 100, SD 11.0) and fewer neurologic deficits than those who had received CFRT or HFRT. However, after statistically controlling for severity of neurologic deficits, treatment had no effect on IQ. The severity of residual neurologic deficits accounted for 42% of the variance in IQ scores; children with fewer neurologic problems scored higher. Additional studies are required to evaluate the potential neuropsychological benefits of equivalent total doses of HFRT compared to CFRT.

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Section: Discussionmentioning

confidence: 77%

Quality of Survival among Children Treated for Brain Stem Glioma

et al. 1994

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“…Craniospinal irradiation still remains an essential component of multimodality therapy for many young children putting these patients at risk for developmental neurotoxicity (14,15). Medulloblastomas are a molecularly heterogeneous group of tumors that can be classified into at least four distinct subgroups: WNT, SHH (Sonic Hedgehog), Group 3, and Group 4 (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages in SHH Subgroup of Medulloblastomas

Margol

Robison

Gnanachandran

et al. 2015

Clinical Cancer Research

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Purpose: Medulloblastoma in children can be categorized into at least four molecular subgroups, offering the potential for targeted therapeutic approaches to reduce treatment-related morbidities. Little is known about the role of tumor microenvironment in medulloblastoma or its contribution to these molecular subgroups. Tumor microenvironment has been shown to be an important source for therapeutic targets in both adult and pediatric neoplasms. In this study, we investigated the hypothesis that expression of genes related to tumorassociated macrophages (TAM) correlates with the medulloblastoma molecular subgroups and contributes to a diagnostic signature.Methods: Gene-expression profiling using human exon array (n ¼ 168) was analyzed to identify medulloblastoma molecular subgroups and expression of inflammation-related genes. Expression of 45 tumor-related and inflammation-related genes was analyzed in 83 medulloblastoma samples to build a gene signature predictive of molecular subgroups. TAMs in medulloblastomas (n ¼ 54) comprising the four molecular subgroups were assessed by immunohistochemistry (IHC).Results: A 31-gene medulloblastoma subgroup classification score inclusive of TAM-related genes (CD163 and CSF1R) was developed with a misclassification rate of 2%. Tumors in the Sonic Hedgehog (SHH) subgroup had increased expression of inflammation-related genes and significantly higher infiltration of TAMs than tumors in the Group 3 or Group 4 subgroups (P < 0.0001 and P < 0.0001, respectively). IHC data revealed a strong association between location of TAMs and proliferating tumor cells.Conclusions: These data show that SHH tumors have a unique tumor microenvironment among medulloblastoma subgroups. The interactions of TAMs and SHH medulloblastoma cells may contribute to tumor growth revealing TAMs as a potential therapeutic target.

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“…Radiation-induced white matter (WM) damage is considered a major contributory factor of treatment-induced neurotoxicity prevalent among childhood cancer survivors who have undergone whole brain irradiation (1). This is manifested as cognitive impairment in cancer survivors months to years after treatment and is of increasing effect because of marked improvements in long-term cancer survival (2).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

et al. 2009

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Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (L // ), and radial diffusivity (L ? ) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in L // from 4 to 40 weeks postradiation, and an increase in L ? with return to baseline in L // at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in L // correlated with reactive astrogliosis (P < 0.01) and L ? correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in L // and L ? . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

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Quality of Life in Children with Primitive Neuroectodermal Tumors (Medulloblastoma) of the Posterior Fossa

Cited by 94 publications

References 11 publications

Quality of Survival among Children Treated for Brain Stem Glioma

Quality of Survival among Children Treated for Brain Stem Glioma

Tumor-Associated Macrophages in SHH Subgroup of Medulloblastomas

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

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