A systematic review and meta-analysis of topoisomerase inhibition in pre-clinical glioma models

Toni Rose Jue, Emily S. Sena, Malcolm R. Macleod, Kerrie L. McDonald and Theodore C. Hirst _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:11387-11401. https://doi.org/10.18632/oncotarget.24334

Metrics: PDF 2247 views  |   HTML 2785 views  |   ?  


Toni Rose Jue1, Emily S. Sena2, Malcolm R. Macleod2, Kerrie L. McDonald1 and Theodore C. Hirst2,3

1Cure Brain Cancer Neuro-Oncology Group, Prince of Wales Clinical School, UNSW Sydney, Australia

2Center for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

3Department of Neurosurgery, Royal Victoria Hospital, Belfast, UK

Correspondence to:

Theodore C. Hirst, email: [email protected]

Keywords: topoisomerase; glioma; systematic review; meta-analysis; meta-regression

Received: September 04, 2017      Accepted: January 20, 2018     Published: January 29, 2018


Malignant glioma is a devastating disease affecting both adults and children with limited treatment strategies. Pre-clinical animal studies are critical to the development and planning of novel treatment designs for human clinical trials. Topoisomerases has been a target of interest in the treatment of high grade gliomas, such as glioblastoma, in the past years. Here we assess pre-clinical glioma literature with the aim to identify predictive variables that favour treatment outcomes from topoisomerase inhibition. Data was extracted from 90 experimental comparisons, this was divided based on available survival (n = 61) and tumor volume (n = 29) data. The meta-analysis revealed that the overall effect of topoisomerase inhibition prolonged survival by a factor of 1.33 (95% CI: 1.23–1.43) and reduced tumor growth by a factor of 3.21 (95% CI: 1.99–5.88), with considerable between-study heterogeneity. Multivariable meta-regression identified glioma model, type of control, route of drug administration and drug of choice to be predictive of improved survival outcome. Publication bias assessment by contour-enhanced funnel plots, Egger’s regression test and trim and fill analysis showed evidence of publication bias in all studies. This study identified multiple study design factors that should be taken into consideration to improve the translation of pre-clinical investigation of topoisomerase inhibition into clinical use.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24334