The efficacy of combination of induction chemotherapy and irreversible electroporation ablation for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. RESULTS: No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. CONCLUSIONS: Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

Safety and Efficacy of Transarterial Radioembolization Combined with Chemoembolization for Bilobar Hepatocellular Carcinoma: A Single-Center Retrospective Study.

BACKGROUND: Radioembolization induced liver disease (REILD) is a possible sequela of transarterial radioembolization (TARE), particularly in cases of whole-liver treatment. To mitigate this problem, the safety and efficacy of combined transarterial chemoembolization (TACE) and TARE were evaluated for patients with bilobar hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Nineteen patients (mean age 60 years; range 27-82 years) treated for HCC between June 2012 and September 2014 were included in the analysis. Each patient was treated with combined TARE and TACE for bilobar HCC, with or without portal vein thrombosis. The hepatic lobe with large HCC was treated with TARE, and the other lobe with small HCC(s) was treated with TACE. Laboratory and clinical data were investigated to determine REILD occurrence. Survival data were analyzed to compare the treatment efficacy of alternative treatment modalities, including TACE and sequential TARE. RESULTS: All patients underwent TARE for a dominant tumor in one lobe and TACE for small nodule(s) in the other lobe of the liver. The mean yttrium-90 microspheres used in TARE were 2.8 GBq (range; 1.0-3.5 GBq), and the mean doses of doxorubicin and iodized oil were 24.5 mg and 5.2 mL, respectively, for TACE. No statistical differences were noted between laboratory data measured before and after treatment, and no procedure-related major clinical complications occurred. The median time-to-progression of patients was 10.0 months, and the median overall survival was 27.3 months. CONCLUSION: Combined radioembolization and chemoembolization appears to be a safe and effective treatment modality for bilobar HCC.

Hepatic arterial damage after transarterial chemoembolization for the treatment of hepatocellular carcinoma: comparison of drug-eluting bead and conventional chemoembolization in a retrospective controlled study.

Background Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) frequently causes feeding artery stenosis or occlusion that may interfere with repeated treatment. Purpose To investigate the incidence and predictors of hepatic arterial damage (HAD) after drug-eluting bead-TACE (DEB-TACE) in comparison with conventional TACE (Conv-TACE). Material and Methods We retrospectively analyzed 54 patients who underwent DEB-TACE for HCC as an initial treatment with follow-up angiography and 54 patients who underwent Conv-TACE using doxorubicin-lipiodol mixture and gelfoam particles for comparison. HAD was evaluated after a single session of TACE and graded as follows: grade I, no significant wall irregularity; grade II, overt stenosis; grade III, occlusion. Results The incidence of HAD was significantly higher in the DEB-TACE group than the Conv-TACE group when analyzed per branch (odds ratio [OR], 6.36; P < 0.001) and per patient (OR, 3.15; P = 0.005). For each HAD grade, the mean doxorubicin dose was greater in the DEB-TACE group than in the Conv-TACE group ( P < 0.001, P = 0.053, and P = 0.01 for grades I, II, and III, respectively). In multivariate analysis, risk factors of HAD included mean doxorubicin dose and selective embolization in the Conv-TACE group ( P = 0.03 and P < 0.001, respectively) and mean doxorubicin dose in the DEB-TACE group ( P = 0.004). Conclusion The incidence and grade of HAD were higher after DEB-TACE compared to Conv-TACE with doxorubicin dose as a possible risk factor. HAD was independent of overall survival in both groups.

Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect.

PURPOSE: To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: New Zealand White rabbits (n = 20) with a VX2 tumor were divided into two groups; one group was treated with hepatic arterial administration of 0.5 mL ethiodized oil alone (Lipiodol; Guerbet, Aulnay-sous-Bois, France) (transarterial embolization with Lipiodol [TAE-L] group), and one group was treated with 0.5 mL ethiodized oil plus 10 mg sorafenib (transarterial embolization with sorafenib [TAE-S] group). Liquid chromatography tandem mass spectrometry was used to measure sorafenib concentration in peripheral blood and tissue. Hepatic enzymes, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were measured at 0, 24, and 72 hours after treatment. Histopathologic examination was performed to evaluate extent of tumor necrosis and normal parenchymal damage. RESULTS: Serum sorafenib concentration peaked at 2 hours after treatment. The mean tissue concentration was 406.8 times greater than the serum concentration. Aspartate aminotransferase and alanine aminotransferase levels were significantly elevated in the TAE-S group at 24 hours after treatment. Serum VEGF and HIF-1α concentrations were not significantly different between the TAE-L and TAE-S groups. Hepatic parenchymal damage was more severe in the TAE-S group. Mean fraction of tumor necrosis after treatment was significantly greater in the TAE-S group. CONCLUSIONS: Transarterial chemoembolization using sorafenib resulted in a high intrahepatic concentration of sorafenib. The degree of tumor necrosis was significantly greater in the TAE-S group compared with the TAE-L group, but more severe toxicity of normal liver tissue also occurred.