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Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry

Overview of attention for article published in Acta Neuropathologica Communications, July 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (73rd percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry
Published in
Acta Neuropathologica Communications, July 2018
DOI 10.1186/s40478-018-0570-9
Pubmed ID
Authors

Hunter C. Gits, Maia Anderson, Stefanie Stallard, Drew Pratt, Becky Zon, Christopher Howell, Chandan Kumar-Sinha, Pankaj Vats, Katayoon Kasaian, Daniel Polan, Martha Matuszak, Daniel E. Spratt, Marcia Leonard, Tingting Qin, Lili Zhao, James Leach, Brooklyn Chaney, Nancy Yanez Escorza, Jacob Hendershot, Blaise Jones, Christine Fuller, Sarah Leary, Ute Bartels, Eric Bouffet, Torunn I. Yock, Patricia Robertson, Rajen Mody, Sriram Venneti, Arul M. Chinnaiyan, Maryam Fouladi, Nicholas G. Gottardo, Carl Koschmann

Abstract

With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3-3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4-17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.

X Demographics

X Demographics

The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 12%
Student > Master 5 12%
Student > Bachelor 5 12%
Student > Doctoral Student 2 5%
Student > Ph. D. Student 2 5%
Other 6 14%
Unknown 17 40%
Readers by discipline Count As %
Medicine and Dentistry 13 31%
Biochemistry, Genetics and Molecular Biology 4 10%
Agricultural and Biological Sciences 3 7%
Neuroscience 2 5%
Chemical Engineering 1 2%
Other 1 2%
Unknown 18 43%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 June 2019.
All research outputs
#4,603,228
of 23,305,591 outputs
Outputs from Acta Neuropathologica Communications
#853
of 1,411 outputs
Outputs of similar age
#87,194
of 330,832 outputs
Outputs of similar age from Acta Neuropathologica Communications
#25
of 40 outputs
Altmetric has tracked 23,305,591 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,411 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 330,832 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.