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@ARTICLE{Weidenbusch:136976,
author = {B. Weidenbusch and G. H. S. Richter and M. S. Kesper and M.
Guggemoos and K. Gall and C. Prexler and I. Kazantsev and A.
Sipol and L. Lindner and M. Nathrath and O. Witt$^*$ and K.
Specht and F. Beitinger and C. Knebel and S. Hosie and R.
von Eisenhardt-Rothe and W. Weichert and I. T. Luettichau
and S. Burdach},
title = {{T}ranscriptome based individualized therapy of refractory
pediatric sarcomas: feasibility, tolerability and efficacy.},
journal = {OncoTarget},
volume = {9},
number = {29},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2018-01404},
pages = {20747-20760},
year = {2018},
abstract = {Survival rates of pediatric sarcoma patients stagnated
during the last two decades, especially in adolescents and
young adults (AYAs). Targeted therapies offer new options in
refractory cases. Gene expression profiling provides a
robust method to characterize the transcriptome of each
patient's tumor and guide the choice of therapy. Twenty
patients with refractory pediatric sarcomas (age 8-35 years)
were assessed with array profiling: ten had Ewing sarcoma,
five osteosarcoma, and five soft tissue sarcoma.
Overexpressed genes and deregulated pathways were identified
as actionable targets and an individualized combination of
targeted therapies was recommended. Disease status,
survival, adverse events (AEs), and quality of life (QOL)
were assessed in patients receiving targeted therapy (TT)
and compared to patients without targeted therapy (non TT).
Actionable targets were identified in all analyzed biopsies.
Targeted therapy was administered in nine patients, while
eleven received no targeted therapy. No significant
difference in risk factors between these two groups was
detected. Overall survival (OS) and progression free
survival (PFS) were significantly higher in the TT group
(OS: P=0.0014, PFS: P=0.0011). Median OS was 8.83 versus
4.93 months and median PFS was 6.17 versus 1.6 months in TT
versus non TT group, respectively. QOL did not differ at
baseline as well as at four week intervals between the two
groups. TT patients had less grade 1 AEs (P=0.009). The
frequency of grade 2-4 AEs did not differ. Overall,
expression based targeted therapy is a feasible and likely
beneficial approach in patients with refractory pediatric
sarcomas that warrants further study.},
cin = {G340},
ddc = {610},
cid = {I:(DE-He78)G340-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29755686},
pmc = {pmc:PMC5945512},
doi = {10.18632/oncotarget.25087},
url = {https://inrepo02.dkfz.de/record/136976},
}