Towards more accurate preclinical glioblastoma modelling: reverse translation of clinical standard of care in a glioblastoma mouse model

Abstract

Introduction: Contrarily to clinical trials, where glioblastoma (GBM) patients are usually heavily pre-treated (surgery, radio-therapy (RT) and temozolomide (TMZ)) before receiving the experimental therapies, in preclinical GBM studies experimental treatments have mostly been administered as monotherapy or combined with a very limited part of the clinical standard of care. This discrepancy can explain the failed clinical translation of preclinically successful treatments. This study is aimed at evaluat-ing the feasibility and survival impact of the clinical standard of care in glioma-bearing mice. Methods. Neurospheres CT-2A tumor-bearing mice were treated with fluorescence-guided tumor resection, focal RT and oral TMZ. Results: The implementation of postoperative intensive care treatment reduced surgical mortality by approximately 50% and increased experimental cost-effectiveness. Partial and total tumor resection significantly prolonged survival, the latter showing the strongest effect. Mice treated with surgery combined with RT or with RT and TMZ survived significantly longer than un-treated controls. Conclusions: Implementing the current GBM clinical standard of care in preclinical research is feasible and it leads to results in line with those obtained in patients. Systematic preclinical evaluation of the efficacy of experimental therapies in combination with standard of care treatments could improve the translational impact of next generation GBM animal studies.

Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models

“…Riva et al [7] studied the clinical SOC in CT-2A tumor-bearing mice. Fluorescence-guided resection was performed on day 14 post-implantation, followed by focal RT (4 Gy) and four doses of TMZ (50 mg/kg) on alternate days starting on day 28.…”

“…Traditionally, novel GBM treatments are screened in preclinical models using treatment-naïve intracranial tumors [6,7]. This approach, however, does not mirror clinical practice, where patients with newly diagnosed GBM undergo resection surgery, followed by RT and chemotherapy.…”