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Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients.

Kohles N, Nagel D, Jüngst D, Durner J, Stieber P, Holdenrieder S - BMC Cancer (2011)

Bottom Line: Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients.The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Chemistry, University-Hospital Munich-Grosshadern, Germany.

ABSTRACT

Background: Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers predicting therapy response are urgently required.

Methods: Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), alpha fetoprotein (AFP), C-reactive protein (CRP) and several liver biomarkers, and to compare these with radiological response to therapy.

Results: While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT) and alkaline phosphatase (AP) significantly indicated the later therapy response (39 progression versus 32 no progression). In multivariate analysis, nucleosomes (24 h), AP (24 h) and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.

Conclusion: Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

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Related in: MedlinePlus

Dot-plots of serum levels of nucleosomes, alkaline phosphatase (AP), alpha fetoprotein (AFP) and gamma-glutamyl-transferase (GGT) with respective medians of patients with response to therapy (○) and those with no response to therapy (●) for all time points during the first day after TACE (★ indicate significant differences).
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Figure 2: Dot-plots of serum levels of nucleosomes, alkaline phosphatase (AP), alpha fetoprotein (AFP) and gamma-glutamyl-transferase (GGT) with respective medians of patients with response to therapy (○) and those with no response to therapy (●) for all time points during the first day after TACE (★ indicate significant differences).

Mentions: The other two cell death parameters LDH and CYFRA 21-1 were increased 24 h after treatment with no significant differences between both groups. However, 3 h and 6 h after TACE, CYFRA 21-1 values showed slightly significant differences (p = 0.041). Just as nucleosomes, CYFRA 21-1 showed decreasing values in both groups after 3 h and 6 h, whereby responders had decreasing levels more often than non-responders. Further markers which differed in the two response groups before and 24 h after TACE were AFP, GGT, AP as well as ALT 3 h and 6 h after TACE (Table 3 and Figure 2).


Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients.

Kohles N, Nagel D, Jüngst D, Durner J, Stieber P, Holdenrieder S - BMC Cancer (2011)

Dot-plots of serum levels of nucleosomes, alkaline phosphatase (AP), alpha fetoprotein (AFP) and gamma-glutamyl-transferase (GGT) with respective medians of patients with response to therapy (○) and those with no response to therapy (●) for all time points during the first day after TACE (★ indicate significant differences).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3118895&req=5

Figure 2: Dot-plots of serum levels of nucleosomes, alkaline phosphatase (AP), alpha fetoprotein (AFP) and gamma-glutamyl-transferase (GGT) with respective medians of patients with response to therapy (○) and those with no response to therapy (●) for all time points during the first day after TACE (★ indicate significant differences).
Mentions: The other two cell death parameters LDH and CYFRA 21-1 were increased 24 h after treatment with no significant differences between both groups. However, 3 h and 6 h after TACE, CYFRA 21-1 values showed slightly significant differences (p = 0.041). Just as nucleosomes, CYFRA 21-1 showed decreasing values in both groups after 3 h and 6 h, whereby responders had decreasing levels more often than non-responders. Further markers which differed in the two response groups before and 24 h after TACE were AFP, GGT, AP as well as ALT 3 h and 6 h after TACE (Table 3 and Figure 2).

Bottom Line: Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients.The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Chemistry, University-Hospital Munich-Grosshadern, Germany.

ABSTRACT

Background: Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers predicting therapy response are urgently required.

Methods: Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), alpha fetoprotein (AFP), C-reactive protein (CRP) and several liver biomarkers, and to compare these with radiological response to therapy.

Results: While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT) and alkaline phosphatase (AP) significantly indicated the later therapy response (39 progression versus 32 no progression). In multivariate analysis, nucleosomes (24 h), AP (24 h) and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.

Conclusion: Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

Show MeSH
Related in: MedlinePlus