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Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients

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Abstract

Standard treatment for patients with primary glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Recent reports have demonstrated that TMZ-induced myelosuppression correlates with survival in patients with GBM. However, those results were evaluated before the 2016 revision of the World Health Organization classification. This study examined whether myelosuppression during concomitant TMZ phase correlates with prognosis in GBM, IDH-wildtype patients. We examined circulating blood cell counts in 50 patients with GBM, IDH-wildtype who received the standard treatment protocol between August 2005 and November 2015. We assessed relationships between rates of decrease in blood cells (white blood cells (WBC), neutrophils, lymphocytes, red blood cells, and platelets) during the concomitant TMZ phase and overall survival (OS) using univariate and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status). Log-rank testing revealed that age, KPS, extent of resection, MGMT status, and decrease rates of WBC, neutrophils, and platelets correlated significantly with OS. On multivariate analysis, age, MGMT status, and decrease rate of neutrophils correlated significantly with OS. Patients with a ≥ 40% decrease in neutrophils showed significantly longer OS than those with < 40% (hazard ratio = 2.815; 95% confidence interval = 1.177–7.038; P = 0.0196). A decrease of ≥ 40% in neutrophils represents a predictor of good prognosis for GBM, IDH-wildtype. Blood cell counts during the concomitant TMZ phase can help predict OS in patients with GBM, IDH-wildtype receiving the standard treatment protocol.

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Acknowledgements

We thank Masako Yoshihiro, Department of Neurosurgery, Hiroshima University, Graduate School of Biomedical and Health Science, Hiroshima, Japan, for the immunohistochemical staining.

Funding

This study was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 26462183.

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Authors and Affiliations

  1. Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Taiichi Saito, Seiji Hama, Fumiyuki Yamasaki, Takeshi Takayasu, Ryo Nosaka & Kaoru Kurisu

  2. Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

    Taiichi Saito, Yoshihiro Muragaki & Takakazu Kawamata

  3. Department of Clinical Oncology and Neuro-oncology Program, Hiroshima University Hospital, Hiroshima, Japan

    Kazuhiko Sugiyama

Authors
  1. Taiichi Saito
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  2. Kazuhiko Sugiyama
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  4. Fumiyuki Yamasaki
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  5. Takeshi Takayasu
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Correspondence to Taiichi Saito.

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Ethical approval

Ethical approval was obtained from the institutional review board of Hiroshima University (No. E-730).

Informed consent

Given the retrospective design, the institutional review board waived the requirement for informed consent. We took the opt-out method. To protect patient privacy, we removed all identifiers from our records upon completion of our analyses.

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The authors declare that they have no conflict of interest.

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Saito, T., Sugiyama, K., Hama, S. et al. Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients. Neurosurg Rev 41, 621–628 (2018). https://doi.org/10.1007/s10143-017-0903-3

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  • DOI: https://doi.org/10.1007/s10143-017-0903-3

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