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Long-term survivors of glioblastoma: clinical features and molecular analysis

  • Clinical Article
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Abstract

Background

Glioblastoma is a highly lethal neoplasm with a median survival of 12–14 months; only 2–5% of patients survive >3 years.

Methods

At our institute, patients with glioblastoma are initially treated with maximum tumor resection followed by radiation and the intravenous injection of nimustine hydrochloride (ACNU).

Results

Using this strategy, 18 of 123 (14.6%) patients treated at our hospital survived >3 years; 7 manifested no recurrence, and the other 11 had early recurrence and received additional therapies. To identify factors associated with prolonged survival, we compared these patients with 21 short-term (<1.5 years) glioblastoma survivors. In the long-term survivors, the MGMT promoter methylation was significantly more frequent. The rate of p53 mutation was lower, and the rate of PTEN mutations and the proliferation index were slightly higher in short-term survivors.

Conclusion

By multivariate analysis, we found that a younger age and MGMT promoter methylation were significant favorable factors in patients with glioblastoma.

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Abbreviations

STS:

short-term survivors

LTS:

long-term survivors

ACNU:

nimustine hydrochloride

MSP:

methylation specific PCR

QRT-PCR:

quantitative real-time reverse transcription PCR

TTP:

time to progression

OS:

overall survival

RS:

radiosurgery

RT:

radiation therapy

ICE:

isfosfamide + cisplatin + etoposide

MTX:

methotrexate

GAPDH:

glyceraldehydes-3-phosphate dehydrogenase

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Acknowledgements

This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare in Japan to T.T. We thank Nippon Gene Research Laboratories Inc. for QRT-PCR and direct sequencing analysis.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan

    Yukihiko Sonoda, Toshihiro Kumabe, Tomoo Inoue, Masayuki Kanamori & Teiji Tominaga

  2. Division of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan

    Mika Watanabe

  3. Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Yoichi Nakazato

Authors
  1. Yukihiko Sonoda
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  2. Toshihiro Kumabe
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  4. Yoichi Nakazato
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  5. Tomoo Inoue
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  6. Masayuki Kanamori
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Correspondence to Yukihiko Sonoda.

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Comment

The most reliable marker in gliomas for biological behavior has been the 1p19q abnormality described in oligodendroglial tumors. Concerning the pure astrocytic tumors, no other marker has been described that has predictive value. Early indications from a few years ago indicated that those patients who received nitrosoureas were more likely to do better if the promoter region of the MGMT gene was methylated. This study seems to corroborate this finding and indeed moves the MGMT promoter methylation status into the forefront in terms of its being predictive for outcome in patients with high-grade gliomas. More retrospective studies are obviously required to decide whether or not this is a robust marker for long- versus short-term survival. This manuscript serves as an excellent substrate on which to base those studies.

Mitchel Berger

San Francisco, CA

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Sonoda, Y., Kumabe, T., Watanabe, M. et al. Long-term survivors of glioblastoma: clinical features and molecular analysis. Acta Neurochir 151, 1349–1358 (2009). https://doi.org/10.1007/s00701-009-0387-1

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