PMID- 29755686
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 29
DP  - 2018 Apr 17
TI  - Transcriptome based individualized therapy of refractory pediatric sarcomas: 
      feasibility, tolerability and efficacy.
PG  - 20747-20760
LID - 10.18632/oncotarget.25087 [doi]
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.
FAU - Weidenbusch, Bushra
AU  - Weidenbusch B
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
FAU - Richter, Gunther H S
AU  - Richter GHS
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
FAU - Kesper, Marie Sophie
AU  - Kesper MS
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
FAU - Guggemoos, Monika
AU  - Guggemoos M
AD  - Department of Pharmacology, Stadtisches Klinikum Munchen GmbH, Munich, Germany.
FAU - Gall, Katja
AU  - Gall K
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
FAU - Prexler, Carolin
AU  - Prexler C
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
FAU - Kazantsev, Ilya
AU  - Kazantsev I
AD  - RM Gorbacheva Scientific Research Institute of Pediatric Hematology and 
      Transplantation, Pavlov First Saint Petersburg State Medical University, Saint 
      Petersburg, Russia.
FAU - Sipol, Alexandra
AU  - Sipol A
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
FAU - Lindner, Lars
AU  - Lindner L
AD  - Department of Hematology/Oncology, Munich University Hospital, 
      Ludwig-Maximilians-Universitat Munchen, Munich, Germany.
FAU - Nathrath, Michaela
AU  - Nathrath M
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - Department of Pediatric Hematology and Oncology, Klinikum Kassel, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
FAU - Witt, Olaf
AU  - Witt O
AD  - Department of Pediatric Oncology, Hematology and Immunology, University Hospital 
      Heidelberg, Heidelberg, Germany.
FAU - Specht, Katja
AU  - Specht K
AD  - Institute of Pathology, Technische Universitat Munchen, Munich, Germany.
FAU - Beitinger, Frigga
AU  - Beitinger F
AD  - Department of Pathology, Stadtisches Klinikum Munchen GmbH, Munich, Germany.
FAU - Knebel, Carolin
AU  - Knebel C
AD  - Department of Orthopedic Surgery, Klinikum rechts der Isar, Fakultat fur Medizin, 
      Technische Universitat Munchen, Munich, Germany.
FAU - Hosie, Stuart
AU  - Hosie S
AD  - Department of Pediatric Surgery, Stadtisches Klinikum Munchen GmbH, Munich, 
      Germany.
FAU - von Eisenhardt-Rothe, Rudiger
AU  - von Eisenhardt-Rothe R
AD  - Department of Orthopedic Surgery, Klinikum rechts der Isar, Fakultat fur Medizin, 
      Technische Universitat Munchen, Munich, Germany.
FAU - Weichert, Wilko
AU  - Weichert W
AD  - Institute of Pathology, Technische Universitat Munchen, Munich, Germany.
FAU - Luettichau, Irene Teichert-von
AU  - Luettichau IT
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
FAU - Burdach, Stefan
AU  - Burdach S
AD  - Department of Pediatrics and Children's Cancer Research Center, Kinderklinik 
      Munchen Schwabing, Klinikum rechts der Isar, Fakultat fur Medizin, Technische 
      Universitat Munchen, Munich, Germany.
AD  - CCC Munchen - Comprehensive Cancer Center; and DKTK German Cancer Consortium 
      Munich, Munich, Germany.
LA  - eng
PT  - Journal Article
DEP - 20180417
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5945512
OTO - NOTNLM
OT  - adolescents and young adults
OT  - expression profiling
OT  - pediatric cancer
OT  - sarcoma
OT  - targeted therapy
COIS- CONFLICTS OF INTEREST S. Burdach has an ownership interest (including patents) in 
      PDL BioPharma. The other authors declare no conflicts of interest.
EDAT- 2018/05/15 06:00
MHDA- 2018/05/15 06:01
PMCR- 2018/04/17
CRDT- 2018/05/15 06:00
PHST- 2017/10/02 00:00 [received]
PHST- 2018/03/05 00:00 [accepted]
PHST- 2018/05/15 06:00 [entrez]
PHST- 2018/05/15 06:00 [pubmed]
PHST- 2018/05/15 06:01 [medline]
PHST- 2018/04/17 00:00 [pmc-release]
AID - 25087 [pii]
AID - 10.18632/oncotarget.25087 [doi]
PST - epublish
SO  - Oncotarget. 2018 Apr 17;9(29):20747-20760. doi: 10.18632/oncotarget.25087. 
      eCollection 2018 Apr 17.