As the field of neuro-oncology makes headway in uncovering the key oncogenic drivers in pediatric glioma, the role of precision diagnostics and therapies continues to rapidly evolve with important implications for the standard of care for clinical management of these patients. Four studies at major academic centers were published in the last year outlining the clinically integrated molecular profiling and targeting of pediatric brain tumors; all 4 demonstrated the feasibility and utility of incorporating sequencing into the care of children with brain tumors, in particular for children and young adults with glioma. Based on synthesis of the data from these studies and others, we provide consensus recommendations for the integration of precision diagnostics and therapeutics into the practice of pediatric neuro-oncology. Our primary consensus recommendation is that next-generation sequencing should be routinely included in the workup of most pediatric gliomas.

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Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were generally assigned a higher BTHT level than simple text questions. The type of microscopy technique (light or electron microscopy) used for these image-based questions did not result in any significant differences in their Bloom's taxonomy scores. The BTHT levels for teacher-generated MCQs correlated positively with higher discrimination indices and inversely with the percent of students answering these questions correctly (difficulty index), suggesting that higher-level Bloom's taxonomy questions differentiate well between higher- and lower-performing students. When examining BTHT scores for MCQs that were written by students in a Multiple-Choice Item Development Assignment (MCIDA) there was no significant correlation between these scores and the students' ability to answer teacher-generated MCQs. This suggests that the ability to answer histology MCQs relies on a different skill set than the aptitude to construct higher-level Bloom's taxonomy questions. However, students significantly improved their average BTHT scores from the midterm to the final MCIDA task, which indicates that practice, experience and feedback increased their MCQ writing proficiency. Anat Sci Educ 10: 456-464. © 2017 American Association of Anatomists.

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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.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0570-9) contains supplementary material, which is available to authorized users.