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@ARTICLE{Steinbgl:170092,
author = {M. Steinbügl and K. Nemes and P. Johann$^*$ and T.
Kröncke and S. Tüchert and M. J. G. da Costa and M.
Ebinger and U. Schüller and A. Sehested and P. Hauser and
H. Reinhard and D. Sumerauer and S. Hettmer and M. Jakob and
M. Hasselblatt and R. Siebert and O. Witt$^*$ and J. Gerss
and K. Kerl and M. C. Frühwald},
title = {{C}linical evidence for a biological effect of
epigenetically active decitabine in relapsed or progressive
rhabdoid tumors.},
journal = {Pediatric blood $\&$ cancer},
volume = {68},
number = {12},
issn = {1545-5017},
address = {New York, NY},
publisher = {Wiley},
reportid = {DKFZ-2021-01755},
pages = {e29267},
year = {2021},
note = {2021 Dec;68(12):e29267},
abstract = {Refined therapy has helped to improve survival rates in
rhabdoid tumors (RT). Prognosis for patients with
chemoresistant, recurrent, or progressive RT remains dismal.
Although decitabine, an epigenetically active agent, has
mainly been evaluated in the management of hematologic
malignancies in adults, safety in children has also been
demonstrated repeatedly.A retrospective series of patients
who received decitabine upon relapse or progression
following therapy according to the EU-RHAB regimen is
presented. Due to the retrospective nature of analyses,
response was defined as measurable regression of at least
one lesion on imaging. 850k methylation profiling was done
whenever tumor tissue was available.A total of 22 patients
with RT of any anatomical localization were included. Most
patients (19/22) presented with metastases. All received
low-dose decitabine with or preceding conventional
chemotherapy. Patients received a median of two (1-6)
courses of decitabine; $27.3\%$ (6/22) demonstrated a
radiological response. Molecular analyses revealed increased
methylation levels in tumors from responders. No excessive
toxicity was observed. Clinical benefits for responders
included eligibility for early phase trials or local
therapy. Responders showed prolonged time to progression and
overall survival. Due to small sample size, statistical
correction for survivorship bias demonstrated no significant
effect on survival for responders.Patients with RT
demonstrate promising signs of antitumor activity after
multiagent relapse therapy including decitabine. Analyses of
methylation data suggest a specific effect on an epigenetic
level. We propose to consider decitabine and other
epigenetic drugs as candidates for further clinical
investigations in RT.},
keywords = {ATRT (Other) / decitabine (Other) / malignant rhabdoid
tumor (Other) / relapsed and refractory rhabdoid tumors
(Other)},
cin = {B062 / B310},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B310-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34347371},
doi = {10.1002/pbc.29267},
url = {https://inrepo02.dkfz.de/record/170092},
}