Super-early initiation of temozolomide prolongs the survival of glioblastoma patients without gross-total resection: a retrospective cohort study

  • Haihui Jiang
  • Wei Zeng
  • Xiaohui Ren
  • Yong Cui
  • Mingxiao Li
  • Kaiyuan Yang
  • Mohammad Elbaroody
  • Song LinEmail author
Clinical Study



The 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.


We retrospectively reviewed the clinical data of 375 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.


Before 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. 9.0 months, P = 0.0384 and OS 23.0 vs. 17.0 months, 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 O6-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).


This retrospective study highlights that super-early initiation of TMZ in newly diagnosed GBM may confer to survival benefit, especially for those without GTR.


Glioblastoma Temozolomide Chemotherapy Super-early Prognosis 



We acknowledge Prof. Xiang Liu for polishing the language of the present paper (Department of Imaging Sciences, University of Rochester Medical Center, Rochester, USA); Dr. Kefu Yu (Beijing Tiantan Hospital, Capital Medical University) and Dr. Yifei Lei (Qingdao University) for collecting part of the clinical data of patients.

Author contributions

Acquisition of Data: HJ, WZ, XR, YC, ML and KY; Analysis and Interpretation of Data: HJ and XR; Statistical analysis: WZ and HJ; Drafting the Article: WZ and HJ; Critically Revising the Article: HJ and ME; funding acquisition: SL; Conception and Design: SL; Study supervision: SL.


This work was supported by National Natural Science Foundation of China (81771309).

Compliance with ethical standards

Conflict of interest

No potential conflict of interest were disclosed.

Supplementary material

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Supplementary material 1 Figure S1. Study flowchart. (JPEG 85 kb)
11060_2019_3211_MOESM2_ESM.doc (77 kb)
Supplementary material 2 (DOC 77 kb)
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Supplementary material 3 (DOC 77 kb)
11060_2019_3211_MOESM4_ESM.doc (58 kb)
Supplementary material 4 (DOC 58 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain DisordersBeijing Key Laboratory of Brain TumorBeijingChina
  2. 2.Department of NeurosurgeryBeijing Electric Power HospitalBeijingChina
  3. 3.Department of NeurosurgeryCairo University HospitalsCairoEgypt

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