Journal of Neuro-Oncology

, Volume 118, Issue 2, pp 239–246 | Cite as

Prognostic utility of gene therapy with herpes simplex virus thymidine kinase for patients with high-grade malignant gliomas: a systematic review and meta analysis

Topic Review


The aim of this study was to assess the effectiveness of adding viral vector-mediated gene therapy with herpes simplex virus thymidine kinase (HSV-tk) to standard treatment, in comparison with standard treatment alone to treat patients with high-grade gliomas (HGGs). A literature search of the databases PubMed, Embase, the Cochrane Library, Web of Science, and Chinese biomedicine was performed to identify eligible studies. Three randomized controlled trials (involving a total of 532 patients) were included in this systematic review. A meta-analysis of included studies demonstrated a significant increase in median survival time (MST) in patients who were treated with HSV-tk gene therapy (mean deviation 0.59, 95 % CI: 0.41–0.76, p < 0.0001). The results of pooled analysis for different patient groups show that overall survival (OS) for all HGG patients was improved by adding gene therapy [hazard ratio (HR) = 0.91, 95 % CI: 0.74–1.13, p = 0.42], while a different result was seen for glioblastoma multiforme (GBM) patients (HR = 1.06, 95 % CI: 0.80–1.41, p = 0.70). Furthermore, the combined results for tumor progression implied that standard therapy was superior to gene therapy [odds ratio (OR) = 1.31, p = 0.09]; yet differences in HR and OR between experimental groups and control groups had no statistical significance (p > 0.05). Based on the best available evidence, it appears that adding gene therapy with HSV-tk has some effect in treating HGG patients, especially with respect to MST. However, neither the pooled analysis of OS, nor the combined analysis of tumor progress indicates any significant advantage to adding gene therapy compared with standard treatment alone. More prospective studies are needed to draw solid conclusions about whether gene therapy has significant prognostic advantage.


High-grade gliomas HSV-tk Gene therapy Meta-analysis 



The authors would like to thank Zheng Li and Bei An (School of Basic Medical Sciences of Lanzhou University, China) for advices on conducting the meta-analysis and writing the article. We also thank two anonymous reviewers and the editor Bharathi Sriram for this article.

Conflicts of interest

The authors indicated no potential conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Fei Zhao
    • 1
    • 2
    • 3
    • 4
  • Jinhui Tian
    • 1
    • 3
  • Lifeng An
    • 4
  • Kehu Yang
    • 1
    • 3
  1. 1.Evidence Based Medicine Center, School of Basic Medical SciencesLanzhou UniversityLanzhouChina
  2. 2.Institution of Integrated Traditional Chinese with Western Medicine, School of Basic Medical SciencesLanzhou UniversityLanzhouChina
  3. 3.Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu ProvinceLanzhouChina
  4. 4.School of MedicineNorthwest University of NationalityLanzhouChina

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