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@ARTICLE{Benesch:143462,
author = {M. Benesch and M. Mynarek and H. Witt$^*$ and M.
Warmuth-Metz and T. Pietsch and B. Bison and S. Pfister$^*$
and K. Pajtler$^*$ and M. Kool$^*$ and U. Schüller and K.
Pietschmann and B.-O. Juhnke and S. Tippelt and G.
Fleischhack and I. Schmid and C. M. Kramm and P. Vorwerk and
A. Beilken and C. F. Classen and P. Hernáiz Driever and G.
Kropshofer and T. Imschweiler and A. Lemmer and R.-D.
Kortmann and S. Rutkowski and K. von Hoff},
title = {{N}ewly {D}iagnosed {M}etastatic {I}ntracranial
{E}pendymoma in {C}hildren: {F}requency, {M}olecular
{C}haracteristics, {T}reatment, and {O}utcome in the
{P}rospective {HIT} {S}eries.},
journal = {The oncologist},
volume = {24},
number = {9},
issn = {1549-490X},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2019-01050},
pages = {E921-E929},
year = {2019},
abstract = {Data on frequency, clinical presentation, and outcome of
primary metastatic intracranial ependymoma in children are
scarce.Prospective data on patients younger than 21 years
with metastatic intracranial ependymoma at first diagnosis,
registered from 2001 to 2014 in the HIT-2000 trial and the
HIT-2000 Interim Registry, were analyzed.Of 453 registered
patients with intracranial ependymoma and central
neuropathology review, initial staging included spinal
magnetic resonance imaging in all patients and lumbar
cerebrospinal fluid (CSF) analysis in 402 patients. Ten
patients $(2.2\%)$ had metastatic disease, including three
with microscopic CSF positivity only (M1 metastasis stage,
$0.7\%$ of patients with CSF staging). Location of the
primary tumor was supratentorial in four patients (all
supratentorial RELA-fused ependymoma [ST-EPN-RELA]) and
within the posterior fossa in five patients (posterior fossa
ependymoma type A [PF-EPN-A], n = 4; posterior fossa
ependymoma not further classifiable, n = 1), and
multifocal in one patient.All four patients with ST-EPN-RELA
were alive in first or second complete remission (CR)
7.5-12.3 years after diagnosis. All four patients with
macroscopic metastases of posterior fossa or multifocal
ependymoma died. Three patients with initial M1 stage
(ST-EPN-RELA, n = 1; PF-EPN-A, n = 2) received
chemotherapy and local irradiation and were alive in second
or third CR 3.0-9.7 years after diagnosis.
Progression-free and overall survival of the entire cohort
at 5 years was $13\%$ $(±6\%),$ and $58\%$ $(±16\%),$
respectively.Primary metastatic disease is rare in children
with intracranial ependymoma. Prognosis may depend on
molecular subgroup and extent of dissemination, and
relevance of CSF analysis for initial staging remains to be
clarified.Childhood ependymoma presenting with metastasis at
first diagnosis is very rare with a frequency of $2.4\%$ in
this population-based, well-characterized cohort. Detection
of microscopic metastases in the cerebrospinal fluid was
extremely rare, and impact on prognosis and respective
treatment decision on irradiation field remains unclear.
Initial metastatic presentation occurs in both
supratentorial RELA-fused ependymoma and posterior fossa
ependymoma. Prognosis may differ according to extent of
metastasis and biological subgroup, with poor prognosis in
diffusely spread metastatic posterior fossa ependymoma even
after combination therapy with both intensive chemotherapy
and craniospinal irradiation, which may help to guide
individual therapeutic decisions for future patients.},
cin = {B062 / L101},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30850560},
doi = {10.1634/theoncologist.2018-0489},
url = {https://inrepo02.dkfz.de/record/143462},
}