Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.     

Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study

Background:

Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new treatment modality. Little is known about prognostic factors affecting survival after DEB TACE for patients with hepatocellular carcinoma (HCC).

Methods:

Patients who underwent TACE with doxorubicin DEB for unresectable HCC during 2006–2008 were studied. Survival was calculated from the day of first transcatheter therapy. Survival analysis was performed using Kaplan–Meier estimations. Survival curves were compared using the log-rank test.

Results:

Fifty patients underwent chemoembolization with doxorubicin DEB. They included 39 women and 11 men, with a median age of 57.5 years (range 28–91 years). Eighteen patients died during the study period and 32 remained alive. Overall survival rates at 6 months, 1 year and 2 years from the first administration of doxorubicin DEB TACE were 71%, 65% and 51%, respectively. Prognostic factors found to be significant on univariate analysis were Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3.0 g/dl, Model for End-stage Liver Disease (MELD) score, serum alphafetoprotein (AFP), Cancer of the Liver Italian Programme (CLIP) score, tumour satisfying Milan criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and Barcelona Clinic Liver Cancer (BCLC) staging.

Conclusions:

Child–Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3 g/dl, MELD score, serum AFP, CLIP score, Milan criteria, ECOG PS and BCLC staging were found to be prognostic markers of survival after treatment with doxorubicin DEB TACE in patients with unresectable HCC.     

Role of additional angiography and chemoembolization in patients with hepatocellular carcinoma who achieved complete necrosis following transarterial chemoembolization

BACKGROUND AND AIMS: Although transarterial chemoembolization (TACE) has been reported to have antitumor effects in patients with hepatocellular carcinoma (HCC), optimal time schedules and follow-up methods have not yet been determined. We therefore prospectively analyzed the effects of additional angiography and chemoembolization on HCC recurrence and survival in patients who underwent TACE and achieved complete necrosis (CN). METHODS: A total of 68 patients who achieved CN after TACE, as assessed using dynamic computed tomography (CT), were randomized into two groups. Patients in the CT group (n = 34) were followed using dynamic CT every 3 months without any further intervention, whereas patients in the angiography group (n = 34) received additional angiography 1 month after achievement of CN. We compared overall survival and disease-free survival between the two groups and analyzed the benefit of additional angiography. RESULTS: The cumulative recurrence rate did not differ between the angiography and CT groups (55%vs 48% at 12 months and 66%vs 67% at 24 months, P = 0.92). The overall survival rates at 12 and 24 months were 88% and 84% in the angiography group, and 88% and 70% in the CT group, respectively (P = 0.57). Of the 34 patients in the angiography group, 27 (79%) suffered from adverse reactions of additional angiography and subsequent chemoembolization, seven (20.6%) experienced serum bilirubin increases of >/=1 mg/dL over baseline, and two (5.9%) developed renal impairment. CONCLUSION: Additional angiography and chemoembolization did not reduce tumor recurrence or improve patient survival in HCC patients who achieved CN, as assessed using dynamic CT, following TACE.     

Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads^®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads^® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads^® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities.     

Doxorubicin-loaded Drug-eluting beads Versus Conventional Transarterial Chemoembolization for Nonresectable Hepatocellular Carcinoma

Background/Aims:To compare the efficacy and safety profile of doxorubicin-loaded drug-eluting beads (DEB) to the conventional TACE (C-TACE) in the management of nonresectable hepatocellular carcinoma (HCC).Results:Thirty-five patients (51 procedures) in the DEB-TACE group and 19 patients (25 procedures) in the c-TACE group were included in the analysis. The median follow up time was 61 days (range 24–538 days) in the DEB-TACE group and 86 days (range 3–152 days) for the c-TACE group patients. Complete response (CR), objective response (OR), disease control (DC), and progressive disease (PD) rates were 11%, 24%, 53%, and 47%, respectively, in the DEB = TACE group compared with 4%, 32%, 64%, and 36%, respectively, in the c-TACE group. Mean ALT change from baseline was minimal in the DEB-TACE patients compared with c-TACE group (7.2 vs 79.4 units, P = 0.001). Hospital stay was significantly shorter in the DEB-TACE group (7.8 days vs 11.4 days; P = 0.038). The 2-year survival rate was 60% for the c-TACE patients and 58% for the DEB-TACE (P = 0.4).Conclusions:DEB-TACE compared with c-TACE is associated with lesser liver toxicity benefit, better tolerance, and shorter hospital stay. The two modalities however had similar survival and efficacy benefits.     

Computed tomography-guided transarterial chemoembolization as the initial therapy for hepatocellular carcinoma: experience of 75 cases in a single institute

We present the survival rates of 75 nonruptured hepatocellular carcinoma cases initially treated with computed tomography-guided transarterial chemoembolization in a single institute. The 1-, 3-, and 5-year survival rates were 93.9%, 74.7%, and 47.4% in 50 Child's A cases; 75.0%, 43.6%, and 6.8% in 20 Child's B cases; and 60.0%, 40.0%, 0.0% in 5 Child's C cases, respectively. The 1-, 3-, and 5-year survival rates of the 38 estimated resectable hepatocellular carcinoma cases (Child's A, tumors limited in a single lobe) were 94.7%, 82.0%, and 44.6%, respectively. The 1-, 3-, and 5-year survival rates of the 41 cases with estimated indication for percutaneous ethanol injection therapy (tumors less than 3 cm in diameter and three or fewer in number) were 96.8%, 84.6%, and 55.5% in 31 Child's A cases; and 90.0%, 46.7%, and 0% in 10 Child's B cases, respectively. In conclusion, computed tomography-guided transarterial chemoembolization is an excellent primary therapy for hepatocellular carcinoma.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.