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BACKGROUND: Posterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long-term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years. METHODS: Demographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome-wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3). RESULTS: A total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10-year progression-free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%-53.1%). Analysis of consecutive 10-year epochs revealed significant improvements in progression-free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full-scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (-1.33 ± 0.42 points/year; P = .0042). CONCLUSIONS: Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time.

MeSH
analýza přežití MeSH
dítě MeSH
ependymom mortalita psychologie terapie MeSH
infratentoriální nádory mortalita psychologie terapie MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
neoadjuvantní terapie škodlivé účinky MeSH
neurochirurgické výkony škodlivé účinky MeSH
neurokognitivní poruchy etiologie MeSH
předškolní dítě MeSH
radioterapie škodlivé účinky MeSH
výsledek terapie MeSH
Check Tag
dítě MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mužské pohlaví MeSH
předškolní dítě MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH
Geografické názvy
Ontario MeSH

Článek

Differential patterns of metastatic dissemination across medulloblastoma subgroups

Journal of neurosurgery. Pediatrics. 2018 ; 21 (2) : 145-152. [pub] 20171208

J. neurosurg. Pediatrics
ISSN 1933-0715
Medvik
Zdroj

OBJECTIVE Metastatic dissemination is a major treatment challenge and cause of death in patients with medulloblastoma. However, the influence of molecular biology on the pattern of metastatic dissemination at diagnosis is not known. In this study, the authors sought to define the location, pattern, and imaging characteristics of medulloblastoma metastases across subgroups at diagnosis. METHODS A consecutive cohort of patients with metastatic medulloblastoma at The Hospital for Sick Children and the University Hospital Motol, who underwent up-front MRI of the craniospinal axis, was assembled and allocated to subgroups using NanoString limited gene-expression profiling. Radiological characteristics (including location, morphology, size, diffusion restriction, and contrast enhancement) were discerned through a retrospective review. RESULTS Forty metastatic medulloblastomas were identified with up-front neuroimaging of the craniospinal axis: 5 sonic hedgehog (SHH), 16 Group 3, and 19 Group 4 metastases. Significant subgroup-specific differences were observed, particularly with respect to tumor location, size, and morphology. Group 3 metastases were most frequently laminar compared with a more nodular pattern in Group 4 (14 of 16 in Group 3 vs 8 of 19 in Group 4; p = 0.0004). Laminar metastases were not observed in patients with SHH medulloblastoma. Suprasellar metastases are highly specific to Group 4 (p = 0.016). Two of the 5 SHH cases had multifocal lesions in the cerebellum, raising the possibility that these were in fact synchronous primary tumors and not true metastases. A minority of patients with Group 4 metastases harbored metastatic deposits that did not enhance on MRI after contrast administration, often in patients whose primary tumor did not enhance. CONCLUSIONS The location, morphology, and imaging characteristics of metastatic medulloblastoma differ across molecular subgroups, with implications for diagnosis and management. This suggests that the biology of leptomeningeal dissemination differs among medulloblastoma subgroups.

MeSH
diferenciální diagnóza MeSH
dítě MeSH
lidé MeSH
magnetická rezonanční tomografie metody MeSH
meduloblastom patologie MeSH
metastázy nádorů MeSH
mnohočetné primární nádory patologie MeSH
nádory mozečku patologie MeSH
neurozobrazování metody MeSH
retrospektivní studie MeSH
Check Tag
dítě MeSH
lidé MeSH
Publikační typ
časopisecké články MeSH
multicentrická studie MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH

Článek

Adolescents and young adults with brain tumors in the context of molecular advances in neuro-oncology

Pediatric blood & cancer. 2018 ; 65 (2) : . [pub] 20171019

Pediatr Blood Cancer
ISSN 1545-5017
Medvik
Zdroj

Adolescents and young adults (AYA) comprise a specific group of oncology patients with a distinct biological and epidemiological spectrum of central nervous system neoplasms. It has been well documented that they differ clinically, especially in relation to prognosis and chemotherapy tolerance; however, the underlying reasons for this are unclear. Recent advances in the genomics of both childhood and adult brain tumors have provided new explanations and insights into the previously described age-dependent heterogeneity. Herein, we summarize the current state of the AYA population in neuro-oncology, specifically how biological advances can help personalize therapy for this unique group of patients.