Open Access Research article

Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

Yvonne Nadine Fahmueller1, Dorothea Nagel1, Ralf-Thorsten Hoffmann24, Klaus Tatsch35, Tobias Jakobs26, Petra Stieber1 and Stefan Holdenrieder17*

Author Affiliations

1 Institute of Clinical Chemistry, University Hospital, Munich - Grosshadern, Germany

2 Institute of Clinical Radiology, University Hospital, Munich - Grosshadern, Germany

3 Clinics of Nuclear Medicine, University-Hospital, Munich-Grosshadern, Germany

4 Institute of Radiological Diagnostics, Hospital of the Technical University, Dresden, Germany

5 Clinics of Nuclear Medicine, Municipial Hospital Karlsruhe, Karlsruhe, Germany

6 Department of Diagnostic and Interventional Radiology, Hospital Brothers of Charity, Munich, Germany

7 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital, Bonn, Germany

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BMC Cancer 2012, 12:5  doi:10.1186/1471-2407-12-5

Published: 4 January 2012

Abstract

Background

Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT.

Methods

Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival.

Results

Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model.

Conclusion

Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.

Keywords:
Colorectal cancer; Selective Internal Radiation Therapy; Therapy response; Nucleosomes; Cancer biomarker