Analytic approaches to clinical validation of results from preclinical models of glioblastoma: a systematic review

Fitt, B.; Loy, G.; Christopher, E.; Brennan, P. M.; Poon, M. T.

Background: Analytic approaches to clinical validation of results from preclinical models are important in assessment of their relevance to human disease. This systematic review examined consistency in reporting of glioblastoma cohorts from The Cancer Genome Atlas (TCGA) and assessed whether studies included patient characteristics in their survival analyses. Methods: We searched Embase and Medline on 02Feb21 for studies using preclinical models of glioblastoma published after Jan2008 that used data from TCGA to validate the association between at least one molecular marker and overall survival in adult patients with glioblastoma. Main data items included cohort characteristics, statistical significance of the survival analysis, and model covariates. Results: There were 58 eligible studies from 1,751 non-duplicate records investigating 126 individual molecular markers. In 14 studies published between 2017 and 2020 using TCGA RNA microarray data that should have the same cohort, the median number of patients was 464.5 (interquartile range 220.5-525). Of the 15 molecular markers that underwent more than one univariable or multivariable survival analyses, five had discrepancies between studies. Covariates used in the 17 studies that used multivariable survival analyses were age (76.5%), pre-operative functional status (35.3%), sex (29.4%) MGMT promoter methylation (29.4%), radiotherapy (23.5%), chemotherapy (17.6%), IDH mutation (17.6%) and extent of resection (5.9%). Conclusions: Preclinical glioblastoma studies that used TCGA for validation did not provide sufficient information about their cohort selection and there were inconsistent results. Transparency in reporting and the use of analytic approaches that adjust for clinical variables can improve the reproducibility between studies.