Dataset Information

A Retrospective Study of Progression-Free and Overall Survival in Pediatric Medulloblastoma Based on Molecular Subgroup Classification: A Single-Institution Experience.

ABSTRACT: BACKGROUND:Medulloblastoma (MB) has been classified into four core subgroups according to the transcriptional profile in recent years. However, some disagreement among researchers remains regarding the prognoses and most effective treatments of the different subgroups with different age distributions. OBJECTIVE:The objective of this study was to analyze MB prognosis in children population based on the classification of four molecular subgroups. METHODS:From January 2011 to January 2013, 84 consecutive MB patients aged underwent tumor removal at Beijing Tiantan Hospital. A total of 55 patients who ranged in age from 4 to 18?years underwent detailed follow-up. Molecular subgrouping was performed using RT-PCR. RESULTS:The 2-year progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 76.2?±?5.8 and 81.8?±?5.2%, respectively. Univariate analysis revealed that the Group 4 patients had a better survival (2-year OS, 90.6?±?5.2%) than the SHH subgroup (P?=?0.002) and Group 3 patients (P?=?0.008). Only two of the 23 non-metastasized Group 4 patients relapsed, and chemotherapy did significantly affect these patients (PFS, P?=?0.685). One out of five WNT patients had tumor relapse and died at last. Large cell/anaplastic (LC/A) histology and chemotherapy were independent risk factors in multivariate analysis. CONCLUSION:In our study, the non-metastasized Group 4 patients had an excellent prognosis. The SHH subgroup and Group 3 patients had worst prognoses. LC/A histology had a dismal prognosis in our cohorts, which warrants intensive treatment.

SUBMITTER: Jiang T

PROVIDER: S-EPMC5427081 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Retrospective Study of Progression-Free and Overall Survival in Pediatric Medulloblastoma Based on Molecular Subgroup Classification: A Single-Institution Experience.

Jiang Tao T Zhang Yuqi Y Wang Junmei J Du Jiang J Raynald Qiu Xiaoguang X Wang Ying Y Li Chunde C

Frontiers in neurology 20170512

<h4>Background</h4>Medulloblastoma (MB) has been classified into four core subgroups according to the transcriptional profile in recent years. However, some disagreement among researchers remains regarding the prognoses and most effective treatments of the different subgroups with different age distributions.<h4>Objective</h4>The objective of this study was to analyze MB prognosis in children population based on the classification of four molecular subgroups.<h4>Methods</h4>From January 2011 to ...[more]

PMID: 28553259

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Project description:"Transcriptionally different" medulloblastoma groups are associated with specific signaling pathway abnormalities; hence, they may present with distinct imaging manifestations. In this study, we sought to describe the MR imaging features of wingless-type-subgroup medulloblastomas with embryologic correlations.Pre- and postoperative imaging studies of 16 patients with wingless-type-subgroup medulloblastoma were evaluated for tumor location, involvement of surrounding CSF spaces or parenchymal structures, conventional and DWI signal properties, and postsurgical damage patterns. Laterality scores were assigned to tumors at each step in the evaluation process. Continuous variables were summarized by using descriptive statistics. The Wilcoxon signed rank test was performed to compare laterality scores. To determine the interobserver variability, we computed the intraclass correlation and Cohen κ coefficients.Wingless-type-subgroup medulloblastomas in our series were histopathologically "classic." Wingless-type-subgroup medulloblastomas occur in specific sites, with involvement of the foramen of Luschka (75%), the fourth ventricle (68.75%), the cisterna magna (31.25%), and the cerebellopontine angle cistern (18.75%). Laterality scores were low (<2) when preoperative primary and secondary anatomic features were evaluated separately, but they increased (>2) when all pre- and postoperative anatomic features were considered. Results were statistically shown to be reproducible (interclass correlation coefficient, 0.71-0.94; Cohen κ, 0.63-1.00). On the basis of anatomic lesion patterns, 4 location-based subtypes may be distinguished: 1) midline-intraventricular, 2) midline-extraventricular, 3) off-midline-intraventricular, and 4) off-midline-extraventricular, which represent a continuum.Wingless-type-subgroup medulloblastomas are lateralized tumors arising from the brain stem and cerebellum around the foramen of Luschka. Our current understanding of their embryologic origins is in concordance with the spatial distribution of these tumors.

Project description:BackgroundUsing a pathway-focused approach, we aimed to provide a subgroup-specific basis for finding novel therapeutic strategies and further refinement of the risk stratification in pediatric medulloblastoma.MethodBased on genome-wide Cox regression and Gene Set Enrichment Analysis, we investigated prognosis-related signaling pathways and core genes in pediatric medulloblastoma subgroups using 530 patient data from Medulloblastoma Advanced Genomic International Consortium (MAGIC) project. We further examined the relationship between expression of the prognostic core genes and frequent chromosome aberrations using broad range copy number change data.ResultsIn SHH subgroup, relatively high expression of the core genes involved in p53, PLK1, FOXM1, and Aurora B signaling pathways are associated with poor prognosis, and their average expression synergistically increases with co-occurrence of losses of 17p, 14q, or 10q, or gain of 17q. In Group 3, in addition to high MYC expression, relatively elevated expression of PDGFRA, IGF1R, and FGF2 and their downstream genes in PI3K/AKT and MAPK/ERK pathways are related to poor survival outcome, and their average expression is increased with the presence of isochromosome 17q [i(17q)] and synergistically down-regulated with simultaneous losses of 16p, 8q, or 4q. In Group 4, up-regulation of the genes encoding various immune receptors and those involved in NOTCH, NF-κB, PI3K/AKT, or RHOA signaling pathways are associated with worse prognosis. Additionally, the expressions of Notch genes correlate with those of the prognostic immune receptors. Besides the Group 4 patients with previously known prognostic aberration, loss of chromosome 11, those with loss of 8q but without i(17q) show excellent survival outcomes and low average expression of the prognostic core genes whereas those harboring 10q loss, 1q gain, or 12q gain accompanied by i(17q) show bad outcomes. Finally, several metabolic pathways known to be reprogrammed in cancer cells are detected as prognostic pathways including glutamate metabolism in SHH subgroup, pentose phosphate pathway and TCA cycle in Group 3, and folate-mediated one carbon-metabolism in Group 4.ConclusionsThe results underscore several subgroup-specific pathways for potential therapeutic interventions: SHH-GLI-FOXM1 pathway in SHH subgroup, receptor tyrosine kinases and their downstream pathways in Group 3, and immune and inflammatory pathways in Group 4.

Dataset Information

A Retrospective Study of Progression-Free and Overall Survival in Pediatric Medulloblastoma Based on Molecular Subgroup Classification: A Single-Institution Experience.

Publications

A Retrospective Study of Progression-Free and Overall Survival in Pediatric Medulloblastoma Based on Molecular Subgroup Classification: A Single-Institution Experience.

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