Abstract
BackgroundTransarterial 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.MethodsVesicle size distribution and concentration were measured by nanoparticle tracking analysis (NTA) in patient sera before and after TACE in 38 patients.ResultsExtracellular 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.SummarySizes (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.
Highlights
Liver tumors represent an enormous medical and socioeconomic problem worldwide
Extracellular vesicle size distribution measured before Transarterial chemoembolization (TACE) is of prognostic significance with respect to overall survival in patients after TACE
Vesicle size was shown to be a significant prognostic marker for overall survival in Cox regression analysis [hazard ratio (HR) 1.089, 95% CI: 1.021–1.162, p = 0.010]
Summary
Liver tumors represent an enormous medical and socioeconomic problem worldwide. In addition to primary liver tumors such as hepatocellular carcinoma, liver metastases from other tumors are responsible for nearly 90% of all malignant liver lesions [1]. Transarterial chemoembolization (TACE) has evolved as a standard treatment option providing an acceptable balance between anti-tumor effect and toxicity both in patients with intermediate stage, unresectable HCC [Barcelona Clinic Liver Cancer (BCLC) stage B] as well as in CRC-patients, when surgery or systemic therapy is considered not appropriate [4, 5]. Pre-interventional stratification for optimal patient selection remains represent an important clinical need in the context of TACE [6, 7]. 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. We evaluate pre-interventional EVs as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies
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