TY  - JOUR
AU  - Weidenbusch, Bushra
AU  - Richter, Günther H S
AU  - Kesper, Marie Sophie
AU  - Guggemoos, Monika
AU  - Gall, Katja
AU  - Prexler, Carolin
AU  - Kazantsev, Ilya
AU  - Sipol, Alexandra
AU  - Lindner, Lars
AU  - Nathrath, Michaela
AU  - Witt, Olaf
AU  - Specht, Katja
AU  - Beitinger, Frigga
AU  - Knebel, Carolin
AU  - Hosie, Stuart
AU  - von Eisenhardt-Rothe, Rüdiger
AU  - Weichert, Wilko
AU  - Luettichau, Irene Teichert-von
AU  - Burdach, Stefan
TI  - Transcriptome based individualized therapy of refractory pediatric sarcomas: feasibility, tolerability and efficacy.
JO  - OncoTarget
VL  - 9
IS  - 29
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2018-01404
SP  - 20747-20760
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29755686
C2  - pmc:PMC5945512
DO  - DOI:10.18632/oncotarget.25087
UR  - https://inrepo02.dkfz.de/record/136976
ER  -