Elsevier

Cancer Treatment Reviews

Volume 38, Issue 1, February 2012, Pages 27-35
Cancer Treatment Reviews

Tumour Review
Diffuse intrinsic pontine gliomas: A systematic update on clinical trials and biology

https://doi.org/10.1016/j.ctrv.2011.06.007Get rights and content

Abstract

Patients with diffuse intrinsic pontine gliomas (DIPG) have a poor prognosis. Although DIPG constitute only 10–15% of all pediatric brain tumors, they are the main cause of death in this group. Despite 26 clinical trials in newly diagnosed DIPG in the past 5 years (including several targeted agents), there is no clear improvement in prognosis. However, knowledge on DIPG biology is increasing, mainly due to the (re)introduction of biopsies and autopsies, the possibility of gene expression profiling, and the development of in vivo models. Translation of this knowledge into clinical trials in combination with improved drug distribution methods may eventually lead to more effective treatment of this devastating disease.

Section snippets

Background

Effective treatment of diffuse intrinsic pontine gliomas (DIPG) in children remains elusive. DIPG comprise 10–15% of childhood brain tumors but are the main cause of death in this young group. Despite several treatment regimens being studied over the last 25 years, prognosis has not improved and <10% of patients are alive two years after diagnosis.1

In 2006, Hargrave et al. reviewed all clinical studies performed in DIPG patients from 1984 to 2005: 29 studies were reported including a total of

Methods

A search was made in PubMed, the Cochrane Central Register of Controlled Trials and Embase covering the period from 1 January 2005 until 1 March 2011. The following terms were used (with synonyms and closely related words): “brain stem” and “gliomas” or “tumors” and “RCT’s” or “reviews” or “meta-analyses” or “systematic reviews” and “children”. Two reviewers (MJ and GJK) independently screened the references for eligible articles by reading the title and abstract. Full-text versions of these

Results

The systematic search on clinical trials yielded 584 publications dating from 2005 (Fig. 1). Unfortunately, although some studies included newly diagnosed DIPG patients, they did not analyze them separately and were therefore excluded from this review.[6], [7]

Table 1 summarizes the inclusion criteria and baseline characteristics, and Table 2 the survival time and response rates for all published clinical studies.

Discussion

The prognosis of DIPG has not improved during the past six years. Only one study, by Frappaz et al. clearly showed an improvement in survival duration: pre-irradiation therapy consisting of high-dose methotrexate, BCNU, cisplatin and tamoxifen until progressive disease occurred, then followed by radiotherapy.12 In that study, the improved survival may have been influenced by the relatively long duration of symptoms (60 days), which may indicate a less aggressive tumor type. The drug combination

Conclusion

No clear improvement in survival has been achieved in DIPG during recent years. Trials still show a wide variation in their inclusion criteria. However, with ever-increasing biological data from in vitro studies, genome-wide analyses and in vivo models, a better basis for future clinical trials has been established. Translation of this knowledge into clinical trials in combination with improved drug distribution and response prediction methods may lead to more effective treatment of this

Conflict of interest

None declared.

Acknowledgments

The authors thank Dr. S. Bailey (Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK) for his critical review of the manuscript and Dr. J.C.F. Ket (Medical Library, VU University Medical Center Amsterdam) for his help in establishing the systematic search.

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