Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma

Krumbholz M, Hellberg J, Steif B, Bäuerle T, Gillmann C, Fritscher T, Agaimy A, Frey B, Juengert J, Wardelmann E, Hartmann W, Juergens H, Dirksen U, Metzler M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Clinical Cancer Research American Association for Cancer Research

Book Volume: 22

Pages Range: 4356-65

Journal Issue: 17

DOI: 10.1158/1078-0432.CCR-15-3028

Abstract

The application of the tumor-specific genomic fusion sequence as noninvasive biomarker for therapy monitoring in Ewing sarcoma (EwS) has been evaluated.EwS xenograft mouse models were used to explore detectability in small plasma volumes and correlation of genomic EWSR1-FLI1 copy numbers with tumor burden. Furthermore, 234 blood samples from 20 EwS patients were analyzed before and during multimodal treatment. EWSR1 fusion sequence levels in patients' plasma were quantified using droplet digital PCR and compared with tumor volumes calculated from MRI or CT imaging studies.Kinetics of EWSR1 fusion sequence copy numbers in the plasma are correlated with changes of the tumor volume in patients with localized and metastatic disease. The majority of patients showed a fast reduction of cell-free tumor DNA (ctDNA) during initial chemotherapy. Recurrence of increasing ctDNA levels signalized relapse development.Genomic fusion sequences represent promising noninvasive biomarkers for improved therapy monitoring in EwS. Until now, response assessment is largely based on MRI and CT imaging, implying restrictions on closely repeated performance and limitations on the differentiation between vital tumor and reactive stromal tissue. Particularly in patients with prognostic unfavorable disseminated disease, ctDNA is a valuable addition for the assessment of therapy response. Clin Cancer Res; 22(17); 4356-65. ©2016 AACR.

Authors with CRIS profile

Manuela Krumbholz Department of Paediatrics and Adolescent Medicine Julia Hellberg Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie Benedikt Steif Department of Paediatrics and Adolescent Medicine Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Clarissa Gillmann Institute of Radiology Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Benjamin Frey Department of Radiation Oncology Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

Involved external institutions

Universitätsklinikum Münster DE Germany (DE)

How to cite

APA:

Krumbholz, M., Hellberg, J., Steif, B., Bäuerle, T., Gillmann, C., Fritscher, T.,... Metzler, M. (2016). Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma. Clinical Cancer Research, 22(17), 4356-65. https://dx.doi.org/10.1158/1078-0432.CCR-15-3028

MLA:

Krumbholz, Manuela, et al. "Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma." Clinical Cancer Research 22.17 (2016): 4356-65.

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