ObjectiveThe optimal timing of chemoradiotherapy in patients with newly diagnosed glioblastoma (GBM) remains unclear. In this study, we explored the clinical efficacy of super-early initiation of temozolomide (TMZ) in the treatment interval from surgery to radiotherapy.MethodsWe retrospectively reviewed the clinical data of375 patients with GBM in our institution from 2012 to 2018. One hundred and sixty-three patients received super-early TMZ within 7 days after craniotomy based on standard Stupp protocol (super-early group, SEG), while two hundred and twelve patients underwent standard Stupp protocol alone (control group, CG). We performed propensity score matching (PSM) to reduce patient selection bias between the two groups.ResultsBefore PSM, both median progression-free survival (PFS) and overall survival (OS) of patients in SEG were longer than those in CG (PFS 11.5 vs. 9.0months, P=0.0384 and OS23.0 vs. 17.0months, P=0.0014). After PSM, the clinical efficacy of super-early initiation of TMZ only remained significant in term of OS, which was further validated in Cox hazard proportional model (HR=0.583, 95% CI 0.384-0.884, P=0.011). In the subgroup analysis, patients without gross total resection (GTR) or with O-6-methylguanine DNA methyltransferase promoter methylation could benefit from super-early initiation of TMZ in both PFS and OS (P<0.05). No significant difference of treatment emerging adverse events was observed between the two groups (P>0.05).ConclusionsThis retrospective study highlights that super-early initiation of TMZ in newly diagnosed GBM may confer to survival benefit, especially for those without GTR.