Enlarged extracellular vesicles are a negative prognostic factor in patients undergoing TACE for primary or secondary liver cancer-a case series.

BACKGROUND: Transarterial chemoembolization (TACE) has evolved as a standard treatment option in patients with intermediate stage, unresectable HCC [Barcelona Clinic Liver Cancer (BCLC) stage B] as well as in patients with liver metastases, when surgery or systemic therapy is considered not appropriate. Concentration and sizes of extracellular vesicles (EVs) recently emerged as novel diagnostic and prognostic biomarkers in patients with liver cancer, but no data on its prognostic relevance in the context of TACE exists. Here, we evaluate pre-interventional EVs as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. METHODS: Vesicle size distribution and concentration were measured by nanoparticle tracking analysis (NTA) in patient sera before and after TACE in 38 patients. RESULTS: Extracellular vesicle size distribution measured before TACE is of prognostic significance with respect to overall survival in patients after TACE. Overall survival is significantly reduced when initial vesicle size (X50) is in the upper quartile (>145.65nm). Median overall survival in patients in the upper quartile was only 314 days, compared to 799 days in patients with vesicle size in the first to third quartile (<145.65nm; p = 0.007). Vesicle size was also shown to be a significant prognostic marker for overall survival in Cox regression analysis [HR 1.089, 95% CI: 1.021-1.162, p = 0.010]. In addition, a significant correlation was observed between initial EVs concentration/BMI (rS = 0.358, p = 0.029), X50/IL-8-concentration (rS = 0.409, p = 0.011) and X50/CRP-concentration (rS = 0.404, p = 0.016). In contrast, with regard to immediate tumor response after TACE, EVs concentration and size did not differ. SUMMARY: Sizes (but not concentrations) of EVs represent a novel prognostic marker in patients receiving TACE for primary and secondary hepatic malignancies since patients with enlarged EVs display a significantly impaired prognosis after TACE.

Macrophage migration inhibitory factor predicts an unfavorable outcome after transarterial chemoembolization for hepatic malignancies.

Transarterial chemoembolization (TACE) is a therapeutic option for patients with intermediate-stage hepatocellular carcinoma (HCC) or metastatic liver cancers. Identifying those patients who particularly benefit from TACE remains challenging. Macrophage migration inhibitory factor (MIF) represents is an inflammatory protein described in patients with liver cancer, but no data on its prognostic relevance in patients undergoing TACE exist. Here, we evaluate MIF serum concentrations as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. MIF serum concentrations were measured by multiplex immunoassay in 50 patients (HCC: n = 39, liver metastases: n = 11) before and 1 day after TACE as well as in 51 healthy controls. Serum concentrations of MIF did not differ between patients and healthy controls. Interestingly, in the subgroup of patients with larger tumor size, significantly more patients had increased MIF concentrations. Patients with an objective tumor response to TACE therapy showed comparable concentrations of serum MIF compared to patients who did not respond. MIF concentrations at day 1 after TACE were significantly higher compared to baseline concentrations. Importantly, baseline MIF concentrations above the optimal cutoff value (0.625 ng/ml) turned out as a significant and independent prognostic marker for a reduced overall survival (OS) following TACE: patients with elevated MIF concentrations showed a significantly reduced median OS of only 719 days compared to patients below the cutoff value (median OS: 1430 days, p = 0.021). Baseline MIF serum concentrations are associated with tumor size of intrahepatic malignancies and predict outcome of patients with liver cancer receiving TACE.

Elevated soluble urokinase plasminogen activator receptor serum levels indicate poor survival following transarterial chemoembolization therapy for hepatic malignancies: An exploratory analysis.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) represents a standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) or liver metastases. However, identification of the ideal candidates for TACE therapy remains challenging. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a prognostic marker in patients with cancer; however no data on suPAR in the context of TACE exists. METHODS: Serum levels of suPAR were measured by an enzyme-linked immunosorbent assay in n = 48 TACE patients (HCC: n = 38, liver metastases: n = 10) before intervention and 1 day after TACE, as well as in 20 healthy controls. RESULTS: Serum levels of suPAR were significantly elevated in patients with liver cancer compared to healthy controls. Patients with or without an objective tumor response to TACE therapy had comparable levels of circulating suPAR. Importantly, baseline suPARs above the ideal prognostic cut-off value (5.39 ng/mL) were a significant prognostic marker for reduced overall survival (OS) following TACE. As such, patients with initial suPAR levels >5.39 ng/mL showed a significantly reduced median OS of only 256 days compared to patients with suPAR serum levels below the cut-off value (median OS: 611 days). In line with previous data, suPAR serum concentrations correlated with those of creatinine but were independent of tumor entity, leukocyte count, and C-reactive protein in multivariate analysis. CONCLUSION: Baseline suPAR serum levels provide important information on the postinterventional outcome of liver cancer patients receiving TACE.