Pediatric diffuse intrinsic pontine glioma: where do we stand?

Rashed, Wafaa M.; Maher, Eslam; Adel, Mohamed; Saber, Ossama; Zaghloul, Mohamed S.

doi:10.1007/s10555-019-09824-2

Cited by 58 publications

(46 citation statements)

References 107 publications

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“…The management strategies other than local irradiation are ineffective, with the benefit of irradiation being transient at best [2]. The anatomic location and infiltrative nature of DIPG severely limit any opportunity for fruitful surgical resection to impact prognosis, and no effective chemotherapy has been reported to improve progression or OS [3, 4]. A previous study reported the long-term survivors of DIPG were aged <3 or >10 years and had long symptom duration, while the short-term survivors presented with symptoms of cranial nerve palsy and had ring enhancement, necrosis, and extrapontine extension on imaging [5].…”

Section: Introductionmentioning

confidence: 99%

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

et al. 2021

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Purpose: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG. Methods: Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex. Results: In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher’s exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test). Conclusion: T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor.

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Section: Introductionmentioning

confidence: 99%

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

et al. 2021

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“…Unfortunately, chemotherapy failed to improve survival in these cases. [ 32 ] Reirradiation is an attractive option to improve the prognosis with minimal toxicity for patients who experience disease progression after radiation therapy. [ 33 ] However, future strategies should be based on our increasing understanding of the radiological, molecular, and clinical characteristics of DIPG, such as mutations that affect the H3 histone variants H3F3A and HIST1H3B.…”

Section: Discussionmentioning

confidence: 99%

Hypofractionated radiotherapy versus conventional radiotherapy for diffuse intrinsic pontine glioma

Park

Yea²

2020

Medicine

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Background: The standard treatment for diffuse intrinsic pontine glioma (DIPG) is radiotherapy, although conventional fractionated radiotherapy (CFRT) may not be in the best interest of the patient. Instead, hypofractionated radiotherapy (HFRT) may shorten the treatment period and reduce related costs for this treatment, which is typically palliative in nature. Methods: This systematic review and meta-analysis evaluated survival outcomes among patients who received HFRT or CFRT for DIPG. The PubMed, Medline, EMBASE, Cochrane Central Register, and Scopus databases were searched to identify relevant studies. Overall survival was the primary outcome of interest and progression-free survival was the secondary outcome of interest. Results: The search identified a total of 2376 reports, although only 4 reports were ultimately included in the meta-analysis. The studies included 88 patients who underwent HFRT and 96 patients who underwent CFRT. Relative to CFRT, HFRT provided comparable outcomes in terms of overall survival (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 0.77–1.47) and progression-free survival (HR: 1.04, 95% CI: 0.75–1.45). Conclusions: The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG.

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“…The 5-year survival rates [ 4 ] for children with cancer in middle- and low-income countries are ~ 55% and ~ 40%, respectively, and survival prospects for several pediatric cancers are still very poor. Children with diffuse intrinsic pontine glioma have a 2-year survival rate of < 20%, with essentially no long-term survivors [ 5 ]. Children with cancer who have recurrent, relapsed, or refractory disease also have very poor survival.…”

Section: Introductionmentioning

confidence: 99%

Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations

et al. 2021

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Regulatory changes have been enacted in the United States (US) and European Union (EU) to encourage the development of new treatments for pediatric cancer. Here, we review some of the factors that have hampered the development of pediatric cancer treatments and provide a comparison of the US and EU regulations implemented to address this clinical need. We then provide some recommendations for each stage of the oncology drug development pathway to help researchers maximize their chance of successful drug development while complying with regulations. A key recommendation is the engagement of key stakeholders such as regulatory authorities, pediatric oncologists, academic researchers, patient advocacy groups, and a Pediatric Expert Group early in the drug development process. During drug target selection, sponsors are encouraged to consult the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the FDA target list, in addition to relevant US and European consortia that have been established to characterize and prioritize oncology drug targets. Sponsors also need to carefully consider the resourcing requirements for preclinical testing, which include ensuring appropriate access to the most relevant databases, clinical samples, and preclinical models (cell lines and animal models). During clinical development, sponsors can account for the pharmacodynamic (PD)/pharmacokinetic (PK) considerations specific to a pediatric population by developing pediatric formulations, selecting suitable PD endpoints, and employing sparse PK sampling or modeling/simulation of drug exposures where appropriate. Additional clinical considerations include the specific design of the clinical trial, the potential inclusion of children in adult trials, and the value of cooperative group trials. Plain Language SummaryIn the last few decades, great progress has been made in developing new treatments for adult cancers. However, development of new treatments for childhood cancers has been much slower. To encourage drug companies (sponsors) to develop effective treatments for childhood cancer, authorities in the United States (US) and Europe have made new rules for drug development. Under these new rules, sponsors developing drugs for specific cancers in adults have to consider whether the target of that drug also causes cancers in children. If this is the case, sponsors have to carry out clinical studies of their drug in children who have cancer that is caused by the same drug target. In this article, we describe some reasons for why drug development for childhood cancers has been slow and the rules created to address this problem in the US and Europe. We share some recommendations to help sponsors maximize their chances of developing an effective drug in children while satisfying the new rules. Specifically, sponsors need to be aware of the differences between studying drugs in adults versus children and how these influence the way the drug is tested. We make several recommendations for each stage of the development process, b...

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Pediatric diffuse intrinsic pontine glioma: where do we stand?

Cited by 58 publications

References 107 publications

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

Hypofractionated radiotherapy versus conventional radiotherapy for diffuse intrinsic pontine glioma

Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations

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