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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

Receiver operating characteristic (ROC) curves indicating the profile of sensitivity and specificity for the estimation of non-response to therapy over the whole range of possible cutoffs for nucleosomes (24 h), alkaline phosphatase (AP 24 h) and the risk score of the combination of both markers and the number of TACE cycle that was identified as best predictive model in multivariate analysis.
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Figure 3: Receiver operating characteristic (ROC) curves indicating the profile of sensitivity and specificity for the estimation of non-response to therapy over the whole range of possible cutoffs for nucleosomes (24 h), alkaline phosphatase (AP 24 h) and the risk score of the combination of both markers and the number of TACE cycle that was identified as best predictive model in multivariate analysis.

Mentions: All univariately relevant biochemical markers measured before (0 h) and 24 h after TACE indicating later therapy response were logarithmized and included, together with clinical factors, into a multivariate logistic regression analysis. Next, the best model of independent predictive markers was identified as combination of nucleosomes (24 h), AP (24 h) and TACE cycle number (Table 4). A similar predictive strength, objectified by Akaike information criterion, was achieved when AP (24 h) was replaced by AFP (24 h). The area under the curve (AUC) of the receiver operating characteristic (ROC) curves for estimation of non-response to therapy was considerably improved when using the risk score based on the combination model (AUC 81.8%) as compared to the single marker nucleosomes (24 h; 71.4%) and AP (24 h; 69.2%; Figure 3). The resulting sensitivities for prediction of non-response to therapy were 41% at 97% specificity, and 72% at 78% specificity using the risk score.


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)

Receiver operating characteristic (ROC) curves indicating the profile of sensitivity and specificity for the estimation of non-response to therapy over the whole range of possible cutoffs for nucleosomes (24 h), alkaline phosphatase (AP 24 h) and the risk score of the combination of both markers and the number of TACE cycle that was identified as best predictive model in multivariate analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Receiver operating characteristic (ROC) curves indicating the profile of sensitivity and specificity for the estimation of non-response to therapy over the whole range of possible cutoffs for nucleosomes (24 h), alkaline phosphatase (AP 24 h) and the risk score of the combination of both markers and the number of TACE cycle that was identified as best predictive model in multivariate analysis.
Mentions: All univariately relevant biochemical markers measured before (0 h) and 24 h after TACE indicating later therapy response were logarithmized and included, together with clinical factors, into a multivariate logistic regression analysis. Next, the best model of independent predictive markers was identified as combination of nucleosomes (24 h), AP (24 h) and TACE cycle number (Table 4). A similar predictive strength, objectified by Akaike information criterion, was achieved when AP (24 h) was replaced by AFP (24 h). The area under the curve (AUC) of the receiver operating characteristic (ROC) curves for estimation of non-response to therapy was considerably improved when using the risk score based on the combination model (AUC 81.8%) as compared to the single marker nucleosomes (24 h; 71.4%) and AP (24 h; 69.2%; Figure 3). The resulting sensitivities for prediction of non-response to therapy were 41% at 97% specificity, and 72% at 78% specificity using the risk score.

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