A twenty-year review of diagnosing and treating children with diffuse intrinsic pontine glioma in The Netherlands

Zanten, Sophie E M Veldhuijzen van; Jansen, Marc; Aliaga, Esther Sánchez; Vuurden, Dannis G. van; Vandertop, W. Peter; Kaspers, Gertjan J. L.

doi:10.1586/14737140.2015.974563

Cited by 46 publications

(36 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the former lack of local hospital- and national registrations, lack of specific ICD-codes1, and due to a presumed limited documentation of clinical, radiological and pathological data, retrospective data collection will very likely be incomplete. Based on data from the Dutch retrospective study [10], and included parties in the SIOPE DIPG Network (with a total number of about 600 million residents aged 0–19 years; April 2016) it is estimated that over 350 children are eligible for prospective registration in the SIOPE DIPG Registry each year. It is expected that annually about 200 patients (60%) will be registered in the first years, and that this number will increase when the SIOPE DIPG Network expands, resulting in higher data completeness per country over time.…”

Section: Discussionmentioning

confidence: 99%

“…First, DIPG is an orphan disease with a yearly incidence of 2.32 per 1,000,000 residents aged 0–20 years [10]. Second, DIPGs are diagnosed clinically, based on typical MR-imaging findings [11], in combination with a classic triad of neurological symptoms [12].…”

Section: Introductionmentioning

confidence: 99%

“…This is exemplified by the recently published new WHO classification of central nervous system tumors, that has reclassified DIPG to the category of WHO grade IV diffuse midline gliomas with histone mutations [15]. Inconsistent definition of DIPG has hampered in- and exclusion or response criteria for clinical trials, which resulted in a great variety of mostly incomparable clinical trials, many of which are single-center, single-arm studies with only few patients enrolled [10]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Zanten¹,

Baugh²,

Chaney³

et al. 2017

J Neurooncol

Self Cite

View full text Add to dashboard Cite

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6–6.4 months) and the median overall survival is 11.0 months (95% CI 10.5–11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-016-2363-y) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Zanten¹,

Baugh²,

Chaney³

et al. 2017

J Neurooncol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients typically present with a brief history of clinical symptoms and signs consistent with brainstem dysfunction, supported by typical radiologic findings on magnetic resonance imaging (MRI) ( Table 1). Clinical signs in over 50% of presentations involve the classical triad of: 1) cranial nerve deficits (most commonly affecting the sixth and seventh cranial nerves resulting in facial asymmetry and diplopia); 2) cerebellar and bulbar signs (ataxia, dysmetria, drooling and dysarthria); and 3) long tract signs (hyperreflexia, upward going Babinski reflex and weakness) [4,5]. Once the diagnosis is confirmed, treatment options are limited.…”

Section: Introductionmentioning

confidence: 99%

Diffuse Intrinsic Pontine Glioma: Translation of Genomic Knowledge to Clinical Practice

hou¹,

Khan²,

Firestein³

et al. 2018

obm neurobiol

View full text Add to dashboard Cite

Pediatric brain tumors account for approximately 25% of all cancers in children and are currently the leading cause of cancer-related deaths in the pediatric population with an estimated incidence of 5.14 cases per 100,000 person years [1]. Up to 10-15% of all pediatric brain tumors arise in the brainstem, with the majority of these classified as the diffuse intrinsic pontine glioma (DIPG) subtype [2]. The outcome of children with DIPG remains dismal with a median survival of <1 year. Owing to the unique location of DIPGs, surgical intervention is unachievable due to difficulty of physical access and the diffuse infiltration of the tumor throughout the pons. Radiotherapy has thus far been the only method identified to provide transient benefit in the setting of a uniformly fatal outcome. Decades of laboratory studies and clinical trials have failed to identify any chemotherapies delivering survival benefit, either alone or as an adjunct to radiotherapy. Advances in surgical biopsy techniques and next generation sequencing modalities have more recently provided a better understanding of the distinct pathophysiology of DIPGs and opened new windows of opportunity for the development of molecular-targeted therapies with hope of delivering more effective treatment for children suffering from DIPG whilst minimizing systemic toxicity. In this review, we will explore the recent advances in the genomic understanding and treatment of DIPG, and the resulting outcomes of the preclinical and clinical drug trials which are guiding the next wave of therapeutic discovery for this disease of unmet clinical need.

show abstract

“…The current DIPG treatment regime consists of radiotherapy that provides only a palliative response for patients and it is well known that cranial radiation alone in children can cause neurological deficits, further prompting the urgent need for the development of more efficacious and less toxic treatment plans for these patients. Presently, median survival for DIPG patients is nine months with mortality rates of 90% by 18 months from diagnosis [7, 8]. These statistics authenticate the clear unmet clinical need for DIPG patients and the requirement for readily translatable treatments.…”

Section: Introductionmentioning

confidence: 99%

Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma

et al. 2017

View full text Add to dashboard Cite

Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting. Subsequently, immunofluorescent staining of neuronal and glial markers was used to determine toxicity in normal rat hippocampal cells. Pre-treatment of cells with sodium valproate enhanced the cytotoxic effects of carboplatin, in three DIPG cell lines tested. These results demonstrate that sodium valproate causes increased histone H3 acetylation indicative of HDAC inhibition, which is inversely correlated with a reduction in cell viability. Cell viability is reduced through an induction of apoptosis in DIPG cells. Sodium valproate potentiates carboplatin cytotoxicity and prompts further work to define the mechanism responsible for the synergy between these two drugs and determine in vivo efficacy. These findings support the use of sodium valproate as an adjuvant treatment for DIPG.

show abstract

A twenty-year review of diagnosing and treating children with diffuse intrinsic pontine glioma in The Netherlands

Abstract: Given the rarity of DIPG, we emphasize the need for (inter-)national trials to facilitate the identification of potentially effective therapeutics in the future. This can be supported by the recent development of a European DIPG registry enabling international study collaborations.

Cited by 46 publications

References 18 publications

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Diffuse Intrinsic Pontine Glioma: Translation of Genomic Knowledge to Clinical Practice

Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma

Contact Info

Product

Resources

About