Preventive treatments for recurrence after curative resection of hepatocellular carcinoma--a literature review of randomized control trials

To review the inhibitory effect of preventive approaches on recurrence after operation in patients with hepatocellular carcinoma (HCC), we summarized all available publications. reporting randomized control trial indexed in PubMed. The treatment approaches presented above included preoperative transcatheter arterial chemoembolization (TACE),post-operative TACE, systemic or locoregional chemotherapy,immunotherapy, Interferons and acyclic retinoic acid Although no standard treatment has been established,several approaches presented promising results, which were both effective and tolerable in post-operative patients. Preoperative TACE was not effective on prolonging survivals,while post-operative TACE was shown with both diseasefree survival and overall survival benefits in some papers,however, it was also questioned by others. Systemic chemotherapy was generally not effective on prolonging survival but also poorly tolerated for its significant toxicities.Adoptive immunotherapy using LAK cells was proved to be beneficial to patients‘ survival in a recent paper. Interferon and Interferon β can inhibit recurrence in HCC patients with HCV infection background, though the mechanism is not fully understood. Acyclic retinoic acid was shown to decrease multi-centric recurrence after operation, which was reported by only one group. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence in HCC patients in randomized control trials; however, multi-centric randomized control trial is still needed for further evaluation on their efficacy and systemic or local toxicities;in addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with HCC after operation.     

Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma： A literature review of randomized control trials

To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.     

Experimental treatment of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most common malignancies world wide. Several experimental treatments have been tested against HCC. Those are chemotherapy, high dose proton beam radiotherapy, external beam radiotherapy, cyberknife, antibody-directed therapy and immunotherapy. Neither single nor combination therapy have demonstrated any clear reproducible benefit in terms of overall survival. Tamoxifen and antiandrogen therapy were not effective in prolonging survival when tested in randomized controlled trial. The modern radiation therapy concept such as intensity-modulated, image-guided, and stereotactic body radiation therapy may show promising effects on HCC. The increasing promise of targeted drug therapy in cancer needs to be particularly pursued in the treatment of HCC, in which cytotoxic agents are not usually effective. Other approaches include hormonal manipulation, immunotherapy, and specific inhibition of angiogenesis or growth factors. These issues stress the need for basic research in carcinogenesis in general and HCC in particular.     

Expanding TACTICS trial into a different setting in hepatocellular carcinoma

Systemic treatment for hepatocellular carcinoma (HCC) is recommended for patients with advanced stage and for those who progressed on locoregional modalities. The first agent approved for advanced HCC was sorafenib, and it remains one of the cornerstones of systemic treatment. In the past years, immunotherapy has shown promising results and has been incorporated into the treatment armamentarium. The rates of recurrence and progression after locoregional therapies are significant, what highlights the need to explore systemic agents for preventing or delaying these negative outcomes. Recently, sorafenib was shown to benefit patients with unresectable HCC under transarterial chemoembolization (TACE) by delaying tumor progression and prolonging time to vascular invasion and extrahepatic spread. Although this result was reported in patients with intermediate stage, it provides background to test the strategy of combining systemic treatment plus TACE as a bridge therapy to HCC patients awaiting liver transplantation, for which the risk of dropout due to tumor progression impairs the possibility of cure.     

Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer. METHODS: Patients with T3-4 and NO-1 esophageal carcinoma from a number of institutions were non-randomly, prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m~2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m~2 and 5-fluorouracil 1000 mg/m~2 for five consecutive days), or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-totreat patients' outcome of survival. RESULTS: A total of 60 patients (n=30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematologicai and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI, 27.5-36.4 vs 15.2-26.1) and 3-year survival (70.0% vs 33.7%; P=0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients. CONCLUSION: For locally advanced esophageal cancer, the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.     

A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma

Purpose  Hepatectomy is considered as the potentially curative treatment for hepatocellular carcinoma (HCC) and used in some selected Stage IIIA HCC, which include multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) (UICC TNM staging system, sixth edition). Transcatheter arterial chemoembolization (TACE) was used in retrospective studies to improve the survival outcome of resected HCC. However, its beneficial effect on the survival outcomes of the Stage IIIA patients has not been evaluated. The present study is to evaluate if hepatectomy combining with adjuvant TACE for Stage IIIA HCC result in better long-term survival outcome when compared with hepatectomy alone. Methods  From January 2001 to March 2004, we conducted a prospective randomized trial in patients with Stage IIIA HCC (NCT00652587), recruiting 115 Stage IIIA HCC patients to undergo hepatectomy with adjuvant TACE (HT arm) or to undergo hepatectomy alone (HA arm) in our cancer center. Survival outcomes of the two arms were analyzed. Results  The demographic data were well matched between the two arms. There were no significant differences in the morbidity and in-hospital mortality between the two arms of patients. The most significant toxicities associated with adjuvant TACE were nausea/vomiting (54.4%) and transient hepatic toxicity (elevation of aminotransferase, 52.6%). Although there was no significant difference in the rate of recurrence between the two arms (50/57 vs. 56/58, P = 0.094), HT arm seemed to have more proportion of single lesion of recurrent HCC (χ ² = 3.719, P = 0.054) and more proportion of potential curative therapy for recurrence (χ ² = 4.456, P = 0.035). Until the time of censor, 92 patients had died. The 1-, 3-, and 5-year overall survival rates and median overall survival for HT arm were 80.7, 33.3, 22.8% and 23.0 months, respectively. The corresponding overall survival rates and median overall survival for HA arm were 56.5, 19.4, 17.5% and 14.0 months, respectively. The difference was significant (stratified log-rank test, P = 0.048). The 1-, 3-, and 5-year disease-free survival rates and median disease-free survival for HT arm were 29.7, 9.3, 9.3% and 6.0 months, respectively; correspondingly, for HA arm were 14.0, 3.5, 1.7% and 4.0 months, respectively (stratified log-rank test, P = 0.004). Conclusions  For Stage IIIA HCC, hepatectomy with adjuvant TACE efficaciously and safely improved survival outcomes when compared with hepatectomy alone.     

根治性肝切除联合索拉非尼治疗肝细胞癌的研究进展

根治性肝切除仍然是肝细胞癌(hepatocellularcarcinoma,HCC)的主要治疗手段,但术后转移复发导致肝切除的疗效进入瓶颈期.探索术后复发的治疗措施是有效延长患者生存时间的重要课题.目前,以经皮肝动脉化疗栓塞为代表的多种治疗措施已在临床广泛开展,但尚缺乏大规模、多中心随机对照临床试验的循证医学证据.分子靶向药物索拉非尼的出现为改善HCC预后开辟了新局面,对于已接受过根治性肝切除治疗的HCC患者,索拉非尼可能是一种有效的辅助治疗方法,值得深入探索.     

Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.     

A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma

BACKGROUND:

The high recurrence rate of hepatocellular carcinoma (HCC) after potentially curative treatment determines the long-term prognosis.

OBJECTIVE:

To evaluate the efficacy and safety of adjuvant therapies in patients with HCC who have undergone hepatic resection, transplantation or locoregional ablation therapy.

METHODS:

Several databases were searched to identify randomized controlled trials (RCTs) fulfilling the predefined selection criteria. Meta-analyses were performed to estimate the effects of adjuvant therapies of any modality on recurrence-free survival (RFS) and overall survival (OS).

RESULTS:

Eight adjuvant modalities were identified from 27 eligible RCTs conducted predominantly in Asian populations comparing adjuvant with no adjuvant therapy. Adjuvant chemotherapy, internal radiation and heparanase inhibitor PI-88 therapy failed to improve RFS or OS, while interferon (IFN) therapy yielded significant survival results. The findings of adjuvant vitamin analogue therapy required further examination. Adjuvant adoptive immunotherapy conferred significant benefit for RFS but not for OS. Although cancer vaccine therapy and radioimmunotherapy may improve survival after radical surgery, the results were from single, small-scale trials. Severe side effects were observed in the studies of adjuvant chemotherapy and of IFN therapy.

CONCLUSIONS:

Adjuvant IFN therapy can improve both RFS and OS; however, the benefits of using this agent should be weighed against its side effects. Combination of systemic and transhepatic arterial chemotherapy is not recommended for HCC after potentially curative treatment. Other adjuvant therapies produce limited success for survival. Additional RCTs with proper design are required to establish the role of adjuvant therapies for HCC.     

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.     

Adjuvant therapy for nonmetastatic osteogenic sarcoma: an evaluation of transfer factor versus combination chemotherapy.

A randomized study compared the effects of combination chemotherapy (high-dose methotrexate, adriamycin, and vincristine) with immunotherapy in the form of transfer factor in the adjuvant treatment of patients with nonmetastatic osteogenic sarcoma after apparent complete surgical ablation of the primary tumor. Thirty-two patients were evaluated. Of 22 patients who received chemotherapy, three died of drug-related complications and six were alive without disease recurrence between 260 and 673 days after operation. Ten patients in the transfer factor group converted their markers, and of these, five were alive without recurrence 420--753 days after operation. Neither treatment program was considered superior with respect to disease-free survival.     

Evolution of systemic therapy of advanced hepatocellular carcinoma

Hepatocellular carcinoma （HCC） commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients. Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.     

吉西他滨联合奥沙利铂经肝动脉化疗栓塞防治肝癌术后复发

目的:探讨吉西他滨联合奥沙利铂经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)在防治肝癌高危患者术后复发中的价值.方法:回顾性分析肝癌术后复发高危患者120例,88例术后3-6wk接受TACE治疗为TACE组,其中43例采用吉西他滨联合奥沙利铂组成的GEMOX方案(GEMOX组),45例使用传统化疗药物方案(对照组);32例因其他原因未接受TACE治疗作为为单纯手术组.通过6mo、12mo的随访,比较各组6mo、12mo术后复发率.结果:TACE组术后6mo、12mo肝内复发率(20.5%、43.8%)明显低于单纯手术组(37.5%、59.4%),两者均有统计学意义(χ2=6.512、4.573,P<0.05).在TACE组中,GEMOX组6mo术后复发率(11.6%)较对照组(28.9%)低,差异有统计学意义(χ2=4.026,P<0.05),两组12mo术后复发率无明显差异(χ2=0.876,P>0.05);在TACE不良反应中,GEMOX组白细胞减少及恶心、呕吐发生率较对照组低,差异有统计学意义(Z=-2.156、-2.295,P<0.05).结论:对肝癌术后复发高危患者进行预防性TACE有助于减少或延缓术后近期复发率,吉西他滨联合奥沙利铂方案疗效更佳.     

Management of hepatocellular carcinoma with transarterial chemoembolization in the era of systemic targeted therapy

The clinical management of hepatocellular carcinoma (HCC) is often complicated by poor liver function. Treatment options for intermediate- and advanced-stage disease are limited. Transcatheter arterial chemoembolization (TACE) is an effective first-line therapy for intermediate-stage HCC. By interrupting blood flow to the tumor and administering concentrated chemotherapy locoregionally, TACE induces necrosis at the tumor site, but may create conditions that permit or encourage angiogenesis and recurrence of the tumor. Combination of TACE with new targeted agents may be an effective way to treat intermediate-stage HCC, particularly in higher risk patients. Because of the efficacy and safety of sorafenib-the first systemic therapy to show significant clinical benefit in advanced HCC-there is great interest in its potential use in combination with existing treatment modalities. The synergistic combination of TACE plus sorafenib represents a promising opportunity for tumor control.     

Adjuvant chemotherapy in colon cancer: what is the evidence?

Abstract
Over the last 12 years, numerous randomized trials have addressed the role of adjuvant chemotherapy in resected colon cancer. Together, these studies give conclusive evidence of the benefit of adjuvant 5‐fluorouracil combined with folinic acid in stage III (node positive) disease and this is now considered the standard of care. The chemotherapy appears to be equally effective whether it is given daily for 5 days per month or on a weekly schedule. The overall effect is a relative reduction in tumour ­recurrence of 25% or an absolute improvement in survival of 10%.
However, doubt remains as to the role of adjuvant chemotherapy in stage II colon cancer. To date, most of the randomized trials have demonstrated a relative reduction in tumour recurrence but have not shown any significant impact on survival. It seems likely that this inability to demonstrate a survival benefit from adjuvant chemotherapy in stage II disease relates to the fact that the trials have been underpowered to do so. Nevertheless, the absolute survival advantage is only about 2% and clinicians need to weigh this against the costs and toxicities of the treatment when managing these patients. (Intern Med J 2003; 33: 119−124)     

肝细胞癌根治术后辅助性肝动脉化疗栓塞对远期复发的影响

目的 研究肝细胞癌根治术后早期(术后2个月内)行辅助性肝动脉化疗栓塞(TACE)对远期复发的影响.方法 2001-2007年行根治性手术切除的2436例肝细胞癌患者纳入本研究.根据术后是否行辅助性TACE治疗分为对照组和干预组;再根据肿瘤直径、数目以及有无镜下癌栓将入选病例分为肿瘤≤5 cm的复发低危、高危组以及肿瘤>5 cm的复发低危、高危组.肿瘤单个且无镜下癌栓为复发低危;否则为复发高危.研究辅助性TACE对各亚组患者远期(>2年)复发的影响.连续性变量用Student't检验比较;分类变量用χ2检验比较;用Kaplan-Meier法统计算生存率和复发率,用Log-rank法比较;用Cox回归模型分析影响患者远期预后的因素. 结果 对照组与干预组术后2年的复发率,在肿瘤≤5 cm的复发低危组分别为20.38%和25.41%,高危组分别为33.06%和39.61%;在肿瘤>5 cm的复发低危组分别为30.54%和40.55%,高危组分别为50.82%和51.57%;各对照组与干预组间的差异均无统计学意义(P>0.05).术后2年内发生复发或死亡患者的中位生存时间,肿瘤>5 cm的复发高危组中,对照组和干预组分别为12个月比24个月;仅在该亚组中,对照组与干预组间生存率差异有统计学意义(χ2=17.59,P<0.01).术后2年内未发生复发和死亡患者的复发率在各对照组与干预组间的差异均无统计学意义(P>0.05);但在肿瘤≤5 cm的复发低危组中,术后3、4、5年的生存率在对照组分别为93.95%、91.50%、88.42%,在干预组分别为91.70%、81.32%、78.19%,差异有统计学意义(χ2=7.48,P<0.05);其他亚组中对照组和干预组间差异均无统计学意义(P>0.05).Cox分析结果 显示,辅助性TACE不是影响远期复发的独立危险因素,但有增加影响这些患者死亡的趋势(HR=1.50,P>0.05).结论 辅助性TACE能够对术后残癌及早期复发灶进行及时诊治,但不能延缓或预防远期复发.对低复发风险(主要是肿瘤≤5 cm的复发低危组)患者给予辅助性TACE治疗可能是弊大于利.     

Adjuvant chemotherapy for resectable biliary tract cancer: current status and future direction

The prognosis of patients with biliary tract cancer remains unsatisfactory even with surgery owing to the high recurrence rate. Therefore, an effective adjuvant chemotherapy is required to prolong survival. A few randomized controlled trials in patients with limited biliary tract cancer have been reported, but the efficacy of adjuvant chemotherapy could not be clarified. To date, effective adjuvant chemotherapy with evidence has not been established, and the standard therapy for patients with resectable biliary tract cancer has only been surgical treatment. Recently, a number of newer toxic agents have been shown to induce response in patients with advanced biliary tract cancer. Moreover, the morbi-mortality rate of operation for this cancer has been decreasing owing to advances in operative techniques and perioperative management. Given this background, a number of adjuvant chemotherapy trials have been started using gemcitabine, capecitabine, S-1, and combination chemotherapy with platinum. The results of these trials will be reported in the near future. Overall, the important aspects of adjuvant chemotherapy for biliary tract cancer are to establish well-organized and active clinical trial study groups, to conduct well-designed multicenter randomized controlled trials, and to continue such trials without interruption in the future.     

Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma

BACKGROUND AND AIM: Adjuvant locoregional chemotherapy has been shown to be useful to prevent recurrence after curative resection of hepatocellular carcinoma (HCC) in some retrospective studies. Our aim was to compare the dose effect in the prevention of tumor recurrence. METHODS: A prospective randomized controlled trial was conducted in patients with curative resection of HCC; they were given either one intra-arterial dose of cisplatin/lipiodol, or received four doses, once every 3 months. The rates of recurrence, disease-free and overall survival were compared. RESULTS: During a median follow up of 818 days, 21 patients received one dose and 19 received four doses, with 10 (47.6%) and eight (42.1%) recurrences, respectively. The 1-year, 2-year and 3-year disease-free survival rates were 71%, 54% and 44% for the one-dose group and 74%, 60% and 40% for the four-dose group (P = 0.78). The respective overall survival rates were 85%, 74%, 55% and 84%, 71%, 40% (P = 0.64). The only prognostic factor was presence of vascular permeation. The side-effects were mild and tolerable. CONCLUSIONS: There is no significant difference in the survival rates between the two groups. Adjuvant chemotherapy may not be useful.     

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.     

Adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma: Propensity score analysis

AIM: To compare survival and recurrence in hepatocellular carcinoma (HCC) patients who did or did not receive adjuvant transarterial chemoembolization (TACE).METHODS: A consecutive sample of 229 patients who underwent curative resection between March 2007 and March 2010 in our hospital was included. Of these 229 patients, 91 (39.7%) underwent curative resection followed by adjuvant TACE and 138 (60.3%) underwent curative resection alone. In order to minimize confounds due to baseline differences between the two patient groups, comparisons were conducted between propensity score-matched patients. Survival data and recurrence rates were compared using the Kaplan-Meier method. Independent predictors of overall survival and recurrence were identified using Cox proportional hazard regression.RESULTS: Among 61 pairs of propensity score-matched patients, the 1-, 2-, and 3-year overall survival rates were 95.1%, 86.7%, and 76.4% in the TACE group and 86.9%, 78.5%, and 73.2% in the control group, respectively. At the same time, the TACE and control groups also showed similar recurrence rates at 1 year (13.4% vs 24.8%), 2 years (30.6% vs 32.1%), and 3 years (40.1% vs 34.0%). Multivariate Cox regression identified serum alpha-fetoprotein level ≥ 400 ng/mL and tumor size > 5 cm as independent risk factors of mortality (P < 0.05).CONCLUSION: As postoperative adjuvant TACE does not improve overall survival or reduce recurrence in HCC patients, further study is needed to clarify its clinical benefit.