Research Papers:

Transcriptome based individualized therapy of refractory pediatric sarcomas: feasibility, tolerability and efficacy

Bushra Weidenbusch, Günther H.S. Richter, Marie Sophie Kesper, Monika Guggemoos, Katja Gall, Carolin Prexler, Ilya Kazantsev, Alexandra Sipol, Lars Lindner, Michaela Nathrath, Olaf Witt, Katja Specht, Frigga Beitinger, Carolin Knebel, Stuart Hosie, Rüdiger von Eisenhardt-Rothe, Wilko Weichert, Irene Teichert-von Luettichau and Stefan Burdach _

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Oncotarget. 2018; 9:20747-20760. https://doi.org/10.18632/oncotarget.25087

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Bushra Weidenbusch1, Günther H.S. Richter1,11, Marie Sophie Kesper1,11, Monika Guggemoos2, Katja Gall1, Carolin Prexler1,11, Ilya Kazantsev4, Alexandra Sipol1, Lars Lindner3, Michaela Nathrath1,6,11, Olaf Witt7, Katja Specht8, Frigga Beitinger9, Carolin Knebel10, Stuart Hosie5, Rüdiger von Eisenhardt-Rothe10, Wilko Weichert8, Irene Teichert-von Luettichau1,11,* and Stefan Burdach1,11,*

1Department of Pediatrics and Children’s Cancer Research Center, Kinderklinik München Schwabing, Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München, Munich, Germany

2Department of Pharmacology, Städtisches Klinikum München GmbH, Munich, Germany

3Department of Hematology/Oncology, Munich University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

4RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia

5Department of Pediatric Surgery, Städtisches Klinikum München GmbH, Munich, Germany

6Department of Pediatric Hematology and Oncology, Klinikum Kassel, Germany

7Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany

8Institute of Pathology, Technische Universität München, Munich, Germany

9Department of Pathology, Städtisches Klinikum München GmbH, Munich, Germany

10Department of Orthopedic Surgery, Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München, Munich, Germany

11CCC München - Comprehensive Cancer Center; and DKTK German Cancer Consortium Munich, Munich, Germany

*Shared senior authorship

Correspondence to:

Stefan Burdach, email: [email protected]

Keywords: targeted therapy; pediatric cancer; sarcoma; adolescents and young adults; expression profiling

Received: October 02, 2017    Accepted: March 05, 2018    Published: April 17, 2018


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.

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