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


CONCLUSIONS
Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.
Institute of Clinical Chemistry, University Hospital, Munich - Grosshadern, Germany.
Yvonne Nadine
YN
Fahmueller
Dorothea
D
Nagel
Ralf-Thorsten
RT
Hoffmann
Klaus
K
Tatsch
Tobias
T
Jakobs
Petra
P
Stieber
Stefan
S
Holdenrieder
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009707:Nucleosomes / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016019:Survival Analysis; D013669:Technetium Tc 99m Medronate / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D009707:Nucleosomes; D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate