Broad-Spectrum Antibiotics are Associated with worse Survival After Radical Treatment for Glioblastoma Multiforme: A Multicentre Study

AIMS: Glioblastoma (GBM) is the most common and aggressive primary brain malignancy in adults. Antibiotic exposure is associated with decreased survival in several solid cancers, but its impact in GBM has not been investigated. We assessed the effect of nonprophylactic antibiotic exposure on survival in patients with GBM receiving radical treatment. MATERIALS AND METHODS: This retrospective cohort study analysed patients with the World Health Organization (WHO) Grade 4 isocitrate dehydrogenase (IDH)-wildtype GBM treated with radiotherapy, with or without concurrent and/or adjuvant temozolomide. Overall survival (OS) was the primary outcome. Antibiotic exposures were recorded from four weeks before radiotherapy until completion of adjuvant chemotherapy, excluding peri-operative, prophylactic and peri-mortem use. RESULTS: In the discovery cohort (N = 234), antibiotic exposure was associated with significantly reduced OS (P = 0.0062). Multivariate and sensitivity analyses (HR = 1.46, P = 0.045), controlling for confounders (eg, corticosteroid exposure, infection occurrence and timing) supported the association. Findings were reproduced in an independent validation cohort (N = 139). Exploratory unpowered subgroup analyses suggest that the adverse effect of antibiotics was most pronounced in patients with a better prognosis. CONCLUSION: Antibiotic exposure during GBM treatment may be associated with reduced survival. Further research evaluating the role of the microbiome in GBM treatment outcomes is warranted. Our results support judicious antibiotic stewardship to maximise therapeutic outcomes.