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