Children's and Adolescents' Medulloblastoma Molecular Subgroups in China

Overview

Recently, diagnosis and treatments for medulloblastoma becomes more complicated than before since the new World Health Organization (WHO) diagnosis criteria has put molecular marker onto an ever important position. Reports and studies revealed highly correlated connection between subgroups of medulloblastoma and patient outcomes. Children's Oncology Group (COG) has launched many new studies on molecular subgroups-based specific treatment trails. In China, children and adolescents with brain tumor have been treated variously for a long time in lack of standardized comprehensive treatments. Same poor situation in basic research and clinical studies makes the Chinese children with brain tumor hardly catch up with international level in molecular diagnosis and specific treatments. There are limited studies, which were conducted by immunohistochemistry for identifying medulloblastoma molecular subgroups, indicating the similar correlation of the subgroups and outcomes to world-wide reports. As the Children's Neuro-Oncology Group (CNOG) was established in China in May 2017, it makes studies from multiple centers in children's brain tumors become practical. And the availability of DNA methylation array, NanoString and other methods in medulloblastoma subgroup identification assures the quality of the method for this study.

Studies discovered that medulloblastoma is a group of tumors with different pathogenesis through different pathways, and majorly can be divided into four molecular subgroups. Moreover, multicenter retrospective studies from US, Canada and European Countries revealed that the molecular subgroup of medulloblastoma becomes an independent correlated risk factor for the patient outcomes. This finding made WHO classification of tumours of central nervous system consider the markers in molecular pathway be an ever important indicator in the new diagnosis criteria. In COG prospective studies for target therapies, subgroup distinguishing becomes indispensable, and the use of immunohistochemistry combined with NanoString, DNA methylation arrays or other molecular methods makes subgroup identification more reliable. In China, there are limited single institutional studies, which were all conducted by immunohistochemistry or polymerase chain reaction (PCR), on molecular sub-grouping of medulloblastoma, especially in pediatric patients. This multicenter retrospective study enrolls children and adolescents (0-18y/o) with primary medulloblastoma from CNOG member institutions across the country, with available paraffin embedded samples and reliable follow-up information, to assess the correlation of molecular subgroups of medulloblastoma and outcomes in Chinese population. This multicenter study recruits eligible patients from CNOG member institutions. Data validation and verification is double conducted by each center and investigators in central data base. Case report form (CRF) was designed by principle investigator and will be modified in the period of uploading first 5 cases by each participated center. The estimated enrollment is 200 cases after sample size assessment. Descriptive statistical analysis, Two-Sample (Independent group) T-Test and one-way ANOVA will be used in epidemiological analysis. Cox-regression / Kaplan-Meier plot will be used in survival analysis. Chi-square test will be used to validate the test efficiency of immunohistochemistry and NanoString methods.