Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

Abstract

Aim: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care.

Methods: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, alpha-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses.

Results: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically.

Conclusion: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.

Figure 1

Stratification algorithm for the treatment of advanced unresectable HCC.

Figure 2

Kaplan-Meier curve showing the survival probabilities of all 101 patients.

Figure 3

Comparison of Kaplan-Meier curves showing the survival probabilities of the four subgroups: TACE-PEI combination, PEI alone, secondary PEI after TACE, secondary PEI after best supportive care. The highest survival probabilities can be expected in the combination treatment group initially stratified to TACE followed by repeated single session PEI.

Figure 4

Comparison of the Kaplan-Meier curves for the parameter maximum tumor diameter (5 cm or less vs more than 5 cm) prior to stratification. The survival probabilities of the subgroup with smaller tumors are significantly higher (logrank: P = 0.02).

Figure 5

Comparison of the Kaplan-Meier curves for the parameter ascites prior to stratification (ascites vs no ascites). Significantly higher survival probabilities can be expected for the subgroup without ascites (logrank: P < 0.001).

Figure 6

Comparison of the Kaplan-Meier curves for the parameter decrease in serum CHE-levels after PEI (decrease >1 mU/mL vs no decrease). The subgroup with stable CHE levels can expect significantly better survival probabilities (logrank: P = 0.02).

Figure 7

Comparison of the Kaplan-Meier curves for the parameter number of tumor lesions (5 or less tumors vs more than 5 tumors). The survival probabilities of the group with 5 or less tumors are significantly higher (logrank: P < 0.05).