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.     

Chemotherapy for transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

AIM: To compare the efficacy of different chemotherapeutic agents during conventional transarterial chemoembolization (cTACE) in the treatment of unresectable hepatocellular carcinoma (HCC).METHODS: A retrospective review was undertaken of patients with unresectable HCC undergoing cTACE from May 2003 to November 2011. A total of 107 patients were treated with at least one cTACE session. Irinotecan (CPT-11) was used as a chemotherapeutic agent in 24 patients, gemcitabine (GEM) in 24 and doxorubicin in 59.RESULTS: The time to progression and overall survival rates were significantly superior in patients treated with CPT-11 compared with the GEM or doxorubicin treated groups (11.4, 8.2, 9.5 mo, P = 0.02 and 21.7, 12.7, 14.5 mo, P = 0.004, respectively). Subgroup analysis showed that for intermediate-stage HCC, CPT-11 resulted in a significantly longer time to progression and overall survival compared with the GEM or doxorubicin treated groups (P = 0.022; P = 0.003, respectively). There were no significant differences in adverse events among the three groups (P > 0.05).CONCLUSION: For patients treated with cTACE, the chemotherapeutic agent CPT-11 was significantly associated with improved overall survival and delayed tumor progression compared with GEM or doxorubicin. There were no significant differences in clinical adverse events between the three agents. CPT-11 thus appears to be a promising agent when combined with cTACE for the treatment of HCC.     

Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta‐analysis

Aim: The efficacy of transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC) is positive, but for postoperative HCC, many studies have reported controversial results. The present study aimed to evaluate the efficacy of postoperative adjuvant TACE for participants with HCC. Methods: Electronic and manual searches were conducted to identify randomized controlled trials (RCT) evaluating postoperative adjuvant TACE for participants with HCC. Results: Six RCT totaling 659 participants, of whom almost all were of stage IIIA HCC, were included. For the 1‐year tumor recurrence rate, hepatectomy plus TACE showed statistically significant less incidence of recurrence, with a pooled risk ratio (RR) of 0.68 (95% confidence interval [CI] = 0.55–0.84, P = 0.0003). For 1‐year mortality, the trials were favorable for TACE with a pooled risk ratio of 0.48 (95% CI = 0.35–0.65, P < 0.00001). For 3‐year mortality, the trials also revealed statistically significant less incidence, with a pooled risk ratio of 0.76 (95% CI = 0.64–0.90, P = 0.002). However, for 5‐year mortality, TACE did not demonstrate statistically significant less incidence (RR = 0.94, 95% CI = 0.81–1.08, P = 0.36). Transient fever and nausea/vomiting were reported as side‐effects of TACE but were well tolerated by most participants. Conclusion: Postoperative adjuvant TACE seems promising for participants with HCC with risk factors (multiple nodules of >5 cm or vascular invasion) but requires further trial.     

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.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization

Background: Ascites is often present in patients with hepatocellular carcinoma (HCC) with cirrhosis. Advanced cirrhosis may predispose to renal dysfunction. Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) for HCC because of radiocontrast agents. This study aimed to investigate the incidence and risk factors of ARF and prognostic predictors in HCC patients with ascites undergoing TACE. Methods: A total of 591 HCC patients receiving TACE were enrolled. Results: In a mean follow‐up duration of 19±17 months, 239 (40.4%) patients undergoing TACE died. Ascites, which was present in 91 (15.4%) patients at entry, independently predicted a poor prognosis in the Cox proportional hazard model [risk ratio (RR): 1.71, P=0.002]. Of these, 11 (12.6%) of 87 patients with complete follow‐up developed ARF after TACE. Serum albumin level <3.3 g/dl (odds ratio: 7.3, P=0.009) was the only independent risk factor associated with ARF in the logistic regression analysis. ARF (RR: 2.17, P=0.036), α‐fetoprotein >400 ng/ml (RR: 1.84, P=0.04), multiple tumours (RR: 2.11, P=0.013), tumour size ≥5 cm (RR: 2.32, P=0.006) and serum sodium level <139 mmol/L (RR: 2.4, P=0.005) were independent poor prognostic predictors for HCC patients with ascites receiving TACE. Conclusions: Pre‐existing ascites is associated with increased mortality in HCC patients receiving TACE. In HCC patients with ascites, hypoalbuminaemia is associated with the occurrence of post‐TACE ARF. Post‐TACE ARF is a poor prognostic predictor in this subset of HCC patients.     

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.     

经肝动脉化疗栓塞术联合索拉非尼治疗中晚期肝细胞癌研究进展

经肝动脉化疗栓塞术(TACE)联合索拉非尼是目前治疗失去手术机会的中晚期肝细胞癌(HCC)最常用的策略,但具体治疗模式还未形成共识。分析了TACE联合索拉非尼治疗HCC的治疗模式及其有效性和安全性。认为不同的治疗模式均具有其利弊,还需要进行更多的临床研究,为中晚期肝癌患者的治疗提供一定参考。     

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.